← Product Code [MNQ](/productcode/MNQ) · P250013 # aura6000™ system (P250013) _LivaNova USA, Inc. · MNQ · Mar 18, 2026 · Anesthesiology · APPR_ **Canonical URL:** https://fda-staging.innolitics.com/device/P250013 ## Device Facts - **Applicant:** LivaNova USA, Inc. - **Product Code:** [MNQ](/productcode/MNQ.md) - **Decision Date:** Mar 18, 2026 - **Decision:** APPR - **Device Class:** Class 3 - **Review Panel:** Anesthesiology - **Attributes:** Therapeutic ## Indications for Use The aura6000™ system is indicated for the reduction of apneas, hypopneas, or both in adult patients with moderate to severe obstructive sleep apnea (OSA), defined as an apnea-hypopnea index (AHI) of ≥ 15 and ≤ 65. The aura6000™ system is intended for patients who failed, do not tolerate, or are ineligible to be treated with current standard of care treatments such as positive airway pressure (PAP), oral appliances (e.g. mandibular advancement device), or pharmacotherapy. ## Device Story The aura6000™ system is an implantable neurostimulator for proximal hypoglossal nerve stimulation (pHGNS) to treat moderate-to-severe OSA. It consists of an implantable pulse generator (IPG) and a lead with a self-sizing cuff electrode placed around the proximal hypoglossal nerve. The system is operated by the patient using a Remote Control/Charger (RCC) and Charging Antenna (CA) to initiate sleep sessions and recharge the IPG. A physician uses the aura Clinical Manager (aCM) software to program stimulation parameters (amplitude, frequency, pulse width) and configure contact groups. The device delivers constant-current, cyclical stimulation to the hypoglossal nerve during sleep, maintaining tongue muscle tone to prevent airway obstruction. This therapy is intended for patients who have failed or are intolerant to PAP therapy. Clinical benefits include reduced AHI and ODI, and improved daytime sleepiness and quality of life. The system is used in a home setting for therapy, with clinical programming performed in a healthcare setting. ## Clinical Evidence Evidence includes four clinical studies (two feasibility, two RCTs) with over 300 subjects. The pivotal OSPREY RCT (N=104) demonstrated superiority of stimulation over control at 7 months, with an AHI responder rate of 58.2% vs 13.5% (p < 0.001). Improvements in ODI, ESS, and FOSQ were statistically significant. Durability was shown through 13 months and up to 5 years in prior studies. Safety profile included mild/transient AEs; 10.6% of subjects required device-related reoperation through 13 months. No deaths or UADEs reported. ## Technological Characteristics Implantable neurostimulator; titanium IPG case; silicone-insulated lead with 6 platinum-iridium electrodes in a self-sizing cuff. Constant-current stimulation; biphasic, charge-balanced waveform. Powered by rechargeable 50mAh Li-ion battery. Connectivity: MedRadio (401-406 MHz) for RCC-IPG, 13.56 MHz inductive charging, USB for aCM programming. Sterilization: Ethylene Oxide (EO). Software: Windows-based aCM for programming; firmware for IPG/RCC. Complies with ISO 14708-1/-3, IEC 60601-1, and ISO 10993-1. ## Reference Devices - Inspire® UAS System - Nyxoah Genio® System ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) # I. GENERAL INFORMATION Device Generic Name: Proximal Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea Device Trade Name: aura6000™ system Device Product code: MNQ Applicant's Name and Address: Livanova USA, Inc. 100 Cyberonics Blvd. Houston, TX 77058 Premarket Approval (PMA) Number: P250013 Date of FDA Notice of Approval: 3/18/2026 # II. INDICATIONS FOR USE The aura6000™ system is indicated for the reduction of apneas, hypopneas, or both in adult patients with moderate to severe obstructive sleep apnea (OSA), defined as an apnea-hypopnea index (AHI) of ≥ 15 and ≤ 65. The aura6000™ system is intended for patients who failed, do not tolerate, or are ineligible to be treated with current standard of care treatments such as positive airway pressure (PAP), oral appliances (e.g. mandibular advancement device), or pharmacotherapy. PAP failure is defined as an inability to eliminate OSA (AHI of greater than 15 despite PAP usage), and PAP intolerance is defined as: - Inability to use PAP (greater than 5 nights per week of usage; usage defined as greater than 4 hours of use per night), or - Unwillingness to use PAP (e.g., a patient returns the PAP system after attempting to use it). # III. CONTRAINDICATIONS - Patients with combined central and mixed apnea-hyponea index greater than or equal to 25% of the total AHI. - Patients with any functional or structural problem, medical illness condition that would prevent or interfere with implantation, activation or continued use of the aura6000™ system. PMA P250013 Summary of Safety and Effectiveness Data Page 1 of 69 {1} - Patients with an implantable device which may be susceptible to unintended interaction with the aura6000™ system. Consult the device manufacturer to assess the possibility of interaction. - Women who are pregnant, planning to become pregnant or breastfeeding. - Patients with any condition or procedure that has compromised neurological control of the upper airway. - Patients who require magnetic resonance imaging (MRI): The generator and lead are MR unsafe devices. MRI exposure may result in dislodgement of implanted components and heating of the generator, lead, and/or electrodes, which may, in turn, cause tissue damage, damage to the device electronics, and/or voltage induction through the lead and generator. The aura6000™ system generator and lead must be explanted if an MRI is required. The Remote Control and Charger (RCC) and Charging Antenna (CA) are MR Unsafe devices. They are projectile hazards that must not be brought into the MR scanner room. - Patients who require diathermy: Shortwave, microwave, and therapeutic ultrasound (hereafter referred to as diathermy) energy can be transferred through the stimulation system, causing damage to the implant and tissue damage, resulting in severe injury or death. Diathermy can also damage system components, resulting in loss of therapy and requiring additional surgery for explantation and replacement. Advise your patient to inform all their healthcare professionals that they must not be exposed to diathermy treatment. Injury to the patient or damage to the system components can occur during diathermy treatment: - Whether the system is on or off - Wherever diathermy is used on the body (not just over the system component) - Whether diathermy delivers heat or not # IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the aura6000™ system instructions for use. # V. DEVICE DESCRIPTION AND INTENDED USE The aura6000™ system is an implantable neurostimulator and lead used for proximal hypoglossal nerve stimulation (pHGNS). The system consists of five components: two implantable components – the aura6000™ Implantable Pulse Generator (IPG) and the lead (with cuff electrode) – and three external components: the Remote Control/Charger (RCC), Charging Antenna (CA), and the aura6000™ Clinical Manager (aCM), an external programming system, which is used to adjust stimulation settings. A description of the implanted and external components of the aura6000™ system is provided below. # A. Mechanism of Action The aura6000™ system provides proximal hypoglossal neurostimulation (pHGNS) by unilaterally stimulating the proximal HGN, which innervates muscles of the tongue (Figure 1). By stimulating the HGN cyclically and continuously during sleep, it maintains the muscle tone of the tongue and upper airway so that obstruction of the airway is reduced or eliminated. PMA P250013 Summary of Safety and Effectiveness Data Page 2 of 69 {2} The therapy leverages the spatial organization of the hypoglossal nerve. Six contacts, helically arranged around the proximal hypoglossal nerve, each connected to an independent constant-current source, allow access and control of the tongue muscles. Cyclical tonic stimulation via multiple electrode contacts, with a maximum duty cycle of 50% (two electrode contacts utilized) and a minimum duty cycle of 16.7% (all six electrode contacts utilized) provides the flexibility to give tonus to the tongue in the desired position relative to the airway. ![img-0.jpeg](img-0.jpeg) Figure 1. aura6000™ Lead Location on the Proximal Hypoglossal Nerve (pHGN) In addition to the general system function and therapeutic mechanism, the following considerations apply to patient selection: A drug-induced sleep endoscopy (DISE) was not required for patient selection for proximal hypoglossal nerve stimulation (pHGNS). In clinical studies, patients with Complete Concentric Collapse (CCC) at the velum level were not excluded; however, CCC status was not systematically assessed or analyzed as a separate subgroup. As a result, the study population may have included individuals with CCC, but outcomes specific to this subgroup were not evaluated. ### B. Model 100.0100 Implantable Pulse Generator (IPG) The implantable pulse generator (IPG) is an implantable, multiprogrammable pulse generator that delivers electrical signals to the hypoglossal nerve. It is housed in a hermetically sealed titanium case and powered by a single rechargeable 50mAh Lithium-Ion battery with an expected battery life of up to 15 years (with nominal settings). It is recommended that the IPG be recharged at least every other day. Recharging typically takes less than 30 minutes but may require up to 90 minutes if the IPG is deeply depleted. The generator is placed under the skin of the upper chest, typically on the right side; however, left side placement is possible when required. The lead is typically attached to the right hypoglossal nerve in the neck. It runs under the skin to connect to the generator. Electrical signals are transmitted through the lead from the generator to the hypoglossal nerve. The lead and generator make up the implantable portion of the aura6000™ system. See Figure 2. PMA P250013 Summary of Safety and Effectiveness Data Page 3 of 69 {3} ![img-1.jpeg](img-1.jpeg) ![img-2.jpeg](img-2.jpeg) Figure 2. A) aura6000™ Implantable Pulse Generator (IPG) and B) aura6000™ Lead ### IPG Intended Use The aura6000™ IPG is intended to provide neurostimulation as a pulse generator with a built-in battery in conjunction with the lead for implantation in a subcutaneous pocket inferior to the collarbone over the pectoralis fascia, typically on the right side. Table 1. aura6000™ IPG General Characteristics | Generator Model 100.0100 | | | --- | --- | | Lead receptacle | 1.5mm | | Dimensions | 47.5 x 33.3 x 9.4mm | | Weight | 16g | | Battery Life | Approximately 15 years (with nominal settings) | | Package Contents | • Generator* • Torque wrench • Suture sleeve | | Material | • Case: Titanium • Header: Epoxy • Torque wrench: Stainless steel, Teflon, Polyethermide thermoplastic | | * The aura6000™ generator is nonpyrogenic. ** No component of aura6000™ system is made with natural rubber latex. | | ### C. Model 300.0100 (25cm) and Model 300.0200 (33cm) Lead The lead delivers the electrical signal from the generator to the proximal hypoglossal nerve and is insulated with silicone. It is designed using medical grade silicone tubing to insulate the MP35N multifilar conductor wires that terminate at the six (6) equally spaced platinum-iridium electrodes (approximately 50° radial spacing) inside the self-sizing nerve cuff which is PMA P250013 Summary of Safety and Effectiveness Data Page 4 of 69 {4} positioned around the proximal hypoglossal nerve. The lead, which is anchored to fascia using the suture sleeve, is available in 2 lengths to ensure optimal fit. The connector end of the lead is tunneled subcutaneously to the generator pocket. The lead is packaged with the torque wrench and suture sleeve. ### Lead Intended Use The aura6000™ Leads (25cm and 33cm) is intended to connect to the IPG on one end and securely placed around the proximal hypoglossal nerve on other end to allow the electrodes to make contact with the nerve to provide neurostimulation. Table 2. aura6000™ Lead General Characteristics | Lead Model 300.0100/300.0200 | | | --- | --- | | Electrode Type | Self-sizing cuff | | Electrode Pattern | 6 contacts, ~50° radial spacing | | Electrode cuff inner | 3.0mm | | Connector | 1.5mm diameter, 2.3mm contact spacing | | Overall Length | 25cm (Model 300.0100) 33cm (Model 300.0200) | | Package Contents | • Lead* • Torque wrench • Suture sleeve | | Material | • Lead Body Insulation: Silicone** • Lead Conductors: ETFE Coated MP35N and Silver • Electrode Connector: Platinum-Iridium • Electrode cuff: Silicone** • Connector Pin: MP35N, Platinum-Iridium and Polyurethane • Suture sleeve: Silicone** | | * The aura6000™ Lead is nonpyrogenic. ** No component of aura6000™ system is made with natural rubber latex. | | ### D. Programming System The external programming system includes the aura6000™ Clinical Manager (aCM), the Remote Control and Charger (RCC), and the Charging Antenna (CA). The aCM is a software application that allows the interrogation and programming of the aura6000™ generator. The aCM communicates with the generator via RCC and a USB cable. Patients are provided with the RCC to start and stop a sleep session and a CA to charge the generator (Figure 3). The RCC also allows patients to adjust patient-specific therapy settings and determine implant status. The RCC battery powers the RCC and the CA. PMA P250013 Summary of Safety and Effectiveness Data Page 5 of 69 {5} ![img-3.jpeg](img-3.jpeg) Figure 3. Patient IPG Charging Configuration # i. Model 700.0100 aura Clinical Manager (aCM) Intended Use The aura Clinical Manager (aCM) is intended for use in conjunction with the implantable components to interrogate and program the IPG. It is intended for use by trained professionals in a hospital or healthcare setting. The aura6000™ Clinical Manager software application is operated on a computer running Microsoft Windows and is used to set the stimulation parameters of the IPG. The aCM communicates with the IPG via the RCC using a USB cable connection. Key Functions: - Surgical implant support: Verify system functionality through impedance testing and motor threshold level determination - Therapy titration: Adjust stimulation parameters during polysomnography (PSG) sessions in both continuous and cyclical modes - Patient follow-up: Modify comfort settings and download usage data - System diagnostics: Interrogate device status, battery levels, and event logs PMA P250013 Summary of Safety and Effectiveness Data Page 6 of 69 {6} ![img-4.jpeg](img-4.jpeg) **Figure 4. aCM Clinical Manager (Home, Surgery, PSG, and Advanced Settings Screens)** The aCM (**Figure 4**) is organized into a series of screens that correspond to the surgical implant procedure (Surgery screen), the titration procedure during which stimulation levels are defined (PSG screen), and the subject follow-up procedure during which comfort adjustments are made (Administration and Advanced Settings screens). The aCM can be used in conjunction with a Polysomnography (PSG) system to optimize therapy settings in real-time by visualizing the active contact being used (1 through 6) and the stimulation amplitude applied on that contact. The aura6000™ system can deliver stimulation through any of the six contacts on the stimulation lead, using either individual contacts or user-defined contact groups. The system provides functionality to evaluate and configure stimulation using one or more contacts. # **ii. Model 500.0300 Charging Antenna (CA) Intended Use** The CA is an external accessory that connects on the top surface of the RCC to charge the IPG. The CA establishes and maintains IPG-to-charging antenna (CA) alignment through a magnetic connection. The IPG must be charged at least every other day, with charging typically taking less than 30 though up to 90 minutes may be required if IPG is deeply discharged. The CA operates at 13.56 MHz and establishes magnetic alignment with the IPG through a magnetic connection. The charging distance is 5-10mm from the CA to the generator. # **iii. Model 500.0100 Remote Control Charger (RCC) Intended Use** The Remote Control Charger (RCC) is intended to be used to interrogate and/or program the generator. The RCC is a handheld device housed in a plastic enclosure with a rechargeable battery pack. It allows patients to: - Start/stop/pause stimulation during sleep sessions PMA P250013 Summary of Safety and Effectiveness Data Page 7 of 69 {7} - Charge the IPG (when used with the Charging Antenna) - Adjust amplitude within physician-prescribed limits (Master Amplitude Control) - Adjust patient preference settings including start delay, pause delay, and sleep duration - Monitor system status including battery levels and therapy usage The RCC communicates wirelessly with the IPG using MedRadio Band (401-406 MHz) at a distance up to 1.5 meters. The RCC also connects to the aCM via USB cable to enable physician programming of the IPG. The RCC battery powers both the RCC and the CA and is recharged by connecting to the provided wall power adapter. ### Communication Interface - Wireless Interface: RCC to IPG communication using CC1101 RF transceivers (MedRadio Band, 401-406 MHz) - Inductive Interface: RCC charges IPG via CA at 13.56MHz - USB Interface: RCC to aCM connection for physician programming - Network Interface: aCM to LivaNova cloud resources for data uploads and software updates. ### iv. Stimulation Parameters The stimulation parameters (Table 3) are controlled by the IPG and programmed using the aura Clinical Manager (aCM). These parameters include pulse amplitude, frequency, and pulse width. The physician configures the stimulation parameters specific for each patient to provide optimal therapy during polysomnography (PSG) titration sessions. Using the RCC, the patient also has the ability to adjust the amplitude within physician-prescribed limits. PMA P250013 Summary of Safety and Effectiveness Data Page 8 of 69 {8} Table 3. aura6000™ system Stimulation Parameters | Parameter | Description | Available Range (step) | Default Setting | | --- | --- | --- | --- | | Waveform | Biphasic, charge-balanced waveform with anodic phase pulse amplitude equal to one-quarter of the cathodic phase pulse amplitude and anodic phase duration equal to four times the cathodic phase duration | N/A | N/A | | Output Current (Amplitude) | Stimulation amplitude | 0 to 1992 μA (12 μA steps) | Physician-determined during titration | | Pulse Frequency | Pulse repetition rate | 3, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, or 90pps | 35 pps | | Pulse Width (Cathodic Phase Duration) | Duration of the cathodic phase stimulation pulse | 50 to 400 μs (25 μs steps) | 200 μs | | Number of Active Contacts | Number of electrode contacts delivering stimulation in sequence | 2 to 6 contacts | Physician-determined (typically 2) | | Duty Cycle | Percentage of time each contact is active | 16.7% (6 contacts) to 50% (2 contacts) | Dependent upon number of contacts determined by physician | | Start Delay | Time between therapy initiation and stimulation onset | 0 to 60 min (15 min increments) | 45 min | | Pause Delay | Time between pause and therapy resumption | 5, 10, 20, or 30min | 20 min | | Sleep Duration | Maximum therapy session duration | 4 to 10 hours (1 hour increments) | 7 hours | Figure 5 below provides a visual representation of the stimulation pulses delivered to the proximal HGN. PMA P250013 Summary of Safety and Effectiveness Data Page 9 of 69 {9} ![img-5.jpeg](img-5.jpeg) **Figure 5. Visual Representation of Therapy Waveform** ## **VI. ALTERNATIVE PRACTICES AND PROCEDURES** Alternative treatment options for patients with moderate to severe OSA include: lifestyle and behavioral approaches such as weight loss or positional therapy; positive airway pressure (PAP) therapies, oral appliances that work by temporarily advancing the mandible to prevent pharyngeal collapse during sleep; pharmacologic options such as glucagon-like peptide (GLP-1) receptor agonist, Tirzepatide, in patients with OSA and obesity, and upper-airway surgical procedures such as maxillomandibular advancement and uvulopalatopharyngoplasty, or bariatric surgery that treats obesity, which is known to worsen OSA symptoms. Implantable hypoglossal nerve stimulation (HGNS) systems are also available treatment options for patients who decline or do not tolerate PAP therapy, including two FDA-approved devices - the Inspire® UAS System and the Nyxoah Genio® System. Each alternative treatment has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the treatment method that best meets their needs. ## **VII. MARKETING HISTORY** The current aura6000™ system has not yet been marketed in any country. The system has not been marketed in the United States. ## **VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH** Potential adverse events from hypoglossal nerve stimulation may include but are not limited to, the following. These events may result in hospitalization, prolongation of hospitalization, unanticipated surgery, tracheotomy, revision or replacement of system components, or death. PMA P250013 Summary of Safety and Effectiveness Data Page 10 of 69 {10} - **Medical/Surgical complications** – Infection; bleeding, hematoma, or seroma; scarring; excessive fibrotic tissue growth around the implanted device; temporary or permanent hypoglossal or other nerve damage resulting in paresis, facial nerve injury (marginal mandibular branch), paralysis or other dysfunction including difficulty or inability to swallow or speak; complications from anesthesia or extended procedure time; persistent pain at the implant site; allergic or immune system response to the implanted materials; and component migration or erosion through the skin. - **Device complications** – Lead migration, dislodgement, disconnection, fracture, insulation breakage or erosion; failure of generator components, battery, software, or telemetry; loss of electrical isolation, and generator migration or flipping. - **Stimulation complications** – Paresthesia (tingling); tongue weakness or movement disturbance, discomfort, pain, or glossodynia (burning sensation); speech disorders, loss of therapeutic effect; extrahypoglossal stimulation; and worsening of OSA condition. For the specific adverse events that occurred in these clinical studies, please see Section X.B.viii. # IX. SUMMARY OF NON-CLINICAL STUDIES Nonclinical testing for the aura6000™ system encompassed a range of evaluations, including bench testing of the device, biocompatibility, sterilization, packaging, shelf-life, software and cybersecurity assessments, electrical safety, electromagnetic compatibility, mechanical, human factors, and animal studies. These tests were conducted in accordance with design specifications, as well as relevant standards and guidance documents. A summary of the results for each test is provided below. # A. aura6000™ Implantable Pulse Generator (IPG) Testing (model 100.0100) Table 4 presents high-level summary results of the aura6000™ IPG testing, with information regarding the test, purpose, applicable acceptance criteria and results. Beyond the testing summarized in Table 4, the IPG design was also reviewed for enhancements implemented to improve electrical isolation. # Summary of IPG Modifications To address electrical isolation issues observed during the OSPREY study, modifications were made to the IPG design and manufacturing process. These included adjustments to the routing of the telemetry and charging coils as part of the isolation improvements. These changes were validated to ensure required electrical isolation. Subsequent verification testing confirmed that these modifications did not alter the electrical, thermal or functional performance of the device. PMA P250013 Summary of Safety and Effectiveness Data Page 11 of 69 {11} Table 4. aura6000™ Implantable Pulse Generator (IPG) Testing Summary | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Functional Testing | Verify IPG contact resistance | Contact resistance shall be less than 1 Ω. | PASS | | | Verify IPG leakage current through dielectric strength testing after preconditioning | Dielectric strength testing at 25.2V after preconditioning shall result in less than 2.356 μA of current leakage. (Following preconditioning by total immersion in 9 g/L saline solution for at least 10 days at 37°C ± 5°C) | PASS | | | Verify IPG leakage current of feedthrough pins after preconditioning | Feedthrough pins shall be insulated and shall allow a maximum leakage current of 2.356 μA between feedthrough pins and from any feedthrough pin to the case. (Following preconditioning by total immersion in 9 g/L saline solution for at least 10 days at 37°C ± 5°C) | PASS | | | Verify IPG exposure to ultrasonic energy | No irreversible change per ISO 14708-1 Clause 22.1 | PASS | | | Verify setscrew torque | Set screw shall achieve ≥5 oz-in torque and the septum shall not dislodge after 10 cycles. | PASS | | | Verify IPG withstand mechanical shock testing | IPG shall meet ISO 14708-1 Clause 23.7. | PASS | | | Verify IPG withstand mechanical vibration testing | IPG shall meet ISO 14708-3 Clause 23.2. | PASS | | Mechanical Design Verification Testing | Verify IPG predicted reliability by conducting mean time to failure (MTTF) calculations | IPG shall have predicted reliability of at least 90% at 5 years. | PASS | | | Verify IPG strain relief tensile force | IPG header strain relief shall withstand a tensile force of 2.22 N. | PASS | | | Verify IPG perpendicular force | IPG header shall withstand a perpendicular force to its planar surface of 133.5 N± 10 N for a period of ≥5 seconds. | PASS | | | Verify IPG welding environment | IPG shall be welded in a 25% ± 5% Helium environment | PASS | | | Verify IPG hermeticity | Helium leak rate shall be <10⁻⁸ cc atm/s after pressurization. | PASS | PMA P250013 Summary of Safety and Effectiveness Data Page 12 of 69 {12} | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | | Verify suture holes are free of functional damage after exposure to 13.3N | No visual appearance of cracks or broken material after applying 13.3 N axial force, 5 second duration | PASS | | Product Shelf Life, Reliability Testing, and Storage Temperature Testing | Verify IPG product shelf life | Verify through accelerated aging, IPG meets its functional requirements after the labeled shelf life | PASS | | | Verify IPG storage temperature | IPG shall endure storage temperature cycles (-10°C to 55°C) with no performance loss per ISO 14708-1 Section 26.2 | PASS | | | Verify IPG sterilization cycles | IPG shall endure 2x sterilization | PASS | | | Verify IPG Temperature increase during maximum stimulation | Temperature increase shall be less than 2°C per ISO 14708-3 Clause 17.1 | PASS | | Resistance to X-Ray | Verify IPG withstands radiography | IPG program settings must remain at factory settings. | PASS | | | Verify IPG x-ray identification | IPG shall have a unique radio-opaque marker or feature identifying the device when examined by x-ray. | PASS | | Battery Testing | Verify IPG battery performance and longevity | Test 1: ≥ 22 cells (simulated real time) must allow single use per day projections. | PASS | | | | Test 2: ≥ 11 cells (accelerated stimulation and idle current) must allow projections using Test 2 data. | PASS | | Atmospheric Pressure Testing | Verify IPG meets the international standards for atmospheric pressure | Meets the requirements of atmospheric pressure per ISO 14708-1 Clause 25.1 | PASS | | Electromagnetic Compatibility (EMC) Testing | Verify the IPG meets international standards for electromagnetic compatibility | Meets requirements of electromagnetic compatibility per ISO 14708-1/-3 Clause 27 and EN 45502-1 | PASS | | Defibrillation Protections | Verify the IPG meets international standards for defibrillation protection | Meets requirements of defibrillation protection requirements per ISO 14708-1 Clause 20.2 | PASS | | Electrocautery Resistance | Verify the IPG meets internal standards for resistance to electrocautery | Meets requirements of resistance to electrocautery per ISO 14708-1 Clause 21.1 | PASS | PMA P250013 Summary of Safety and Effectiveness Data Page 13 of 69 {13} # **B. aura6000™ Lead Testing (models 300.0100, and 300.0200)** Table 5 presents high-level summary results of the aura6000™ Lead testing, with information regarding the test, purpose, applicable acceptance criteria and results. Additional analyses were conducted to evaluate safety aspects related to the stimulation configuration. # **Summary of Monopolar Stimulation Analysis** An analysis was performed to characterize the potential for off-target effects from current spread associated with pHGNS, a monopolar approach to stimulation of the hypoglossal nerve used in the treatment of OSA with the aura6000™ system. This evaluation included anatomical review of structures adjacent to the proximal hypoglossal nerve, computational modeling of electric field distribution including worst-case proximity modeling this adjacency, and assessment of stimulation-related adverse events observed during clinical use. Modeling showed that adjacent nerves would require currents substantially higher than the maximum output of the device to reach activation thresholds, indicating a low likelihood of unintended stimulation. Clinical observations were consistent with this finding, with no serious adverse events attributed to activation of off-target structures. **Table 5. aura6000™ Lead Testing Summary** | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | **Tensile Load Testing** | Verify the lead tensile force | Cuff electrode shall withstand a tensile force of up to 5 N with no loss of performance. *(Following preconditioning by total immersion in 9 g/L saline solution for at least 10 days at 37°C ± 5°C)* | PASS | | **Fatigue Testing** | Verify the lead connector flexural fatigue | The lead connector shall withstand 82,000 flex cycles without conductor fracture per BS EN 45502-1: 2015 Section 23.5; BS EN 45502-2-1: 2003 Section 23.5 | PASS | | | Verify the lead body flexural fatigue | After ≥ 235,000 cycles, pass visual inspection per specification. No damage to the coil wires or tubing and pass electrical test per BS EN 45502-1: 2015 Section 23.5; BS EN 45502-2-1: 2003 Section 23.5 | PASS | | | Verify the lead transition flex fatigue | Must withstand ≥ 82,000 cycles, and lower bound of the one-sided 95/95 tolerance interval must be > 82,000 per BS EN 45502-1: 2015 Section 23.5; BS EN 45502-2-1: 2003 Section 23.5 | PASS | | **Insertion and Extraction Testing** | Verify the lead maximum insertion force | The lead shall require an insertion force of less than 10 N (2.2 lbf) to be fully inserted into the IPG header. | PASS | PMA P250013 Summary of Safety and Effectiveness Data Page 14 of 69 {14} | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | | Verify the lead maximum extraction force | The lead shall require a maximum extraction force of less than 10 N (2.2 lbf) to be fully removed from the IPG header. | PASS | | | Verify the lead minimum extraction force | The connector shall require a minimum of 10 N (2.2 lbf) to extract the lead from the IPG when the setscrew is engaged. Resistance measurement for each lead channel shall be < 20 ohms and no damage or component detachment present. Re-connection shall be possible without degradation in performance. | PASS | | | Verify the lead withstands repeated insertions | All insertion and extraction requirements listed above must be met after 10 repeated insertion/withdrawal cycles. | PASS | | **Electrical Performance Testing** | Verify the lead allowable leakage is minimized in dry conditions | Current leakage between contacts in dry conditions shall be < 10 μA at 100 VDC. | PASS | | | Verify the lead allowable leakage is minimized in in-vivo conditions | Current leakage between an active contact and any other contact/saline shall be < 2 mA, *(Following preconditioning by total immersion in 9 g/L saline solution for at least 10 days at 37°C ± 5°C and testing at 100V)* | PASS | | | Verify the lead contact-connector and disk electrode resistance | Resistance shall be < 20 Ω. | PASS | | **Resistance to X-Ray** | Verify the lead resistance to x-ray | Cuff electrode shall withstand radiography with no loss of performance. | PASS | | **Product Shelf Life, Reliability Testing, and Storage Temperature Testing** | Verify the lead product shelf life | Verify the lead meets its functional requirements after the labeled shelf life | PASS | | | Verify the lead storage temperature | Lead shall endure 2x sterilization and storage temperature cycles (-10°C to 55°C) with no performance loss. | PASS | | | Verify the lead sterilization cycles | Lead shall endure 2x sterilization and storage temperature cycles (-10°C to 55°C) with no performance loss. | PASS | PMA P250013 Summary of Safety and Effectiveness Data Page 15 of 69 {15} | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | **Corrosion Testing** | Verify material integrity of the lead following exposure to simulated use conditions and environments. | No trace element changes between control samples and test articles. *(Following preconditioning by total immersion in 9 g/L saline solution for at least 10 days at 37°C ± 5°C)* | PASS | | **Atmospheric Pressure Testing** | Verify the lead meets the international standards for atmospheric pressure | Meets the requirements of atmospheric pressure per ISO 14708-1 Clause 25.1 | PASS | | **Electromagnetic Compatibility (EMC) Testing** | Verify the lead meets international standards for electromagnetic compatibility | Meets requirements of electromagnetic compatibility per ISO 14708-1/-3 Clause 27 and EN 45502-1 | PASS | # **C. aura6000™ Charging Antenna (CA) (model 500.0300) and Remote Control and Charger (RCC) (model 500.0100) Testing** Table 6 presents high-level summary results of the aura6000™ CA and RCC testing, with information regarding the test, purpose, applicable acceptance criteria and results. **Table 6. Charging Antenna (CA) and Remote Control and Charger (RCC) Testing Summary** | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | **CA Storage Temp and Humidity Testing** | Verify the CA maintains performance after exposure to storage temperature and humidity extremes. | CA shall meet performance requirements at storage temperatures between -10°C to 55°C and ≤ 95% humidity (non-condensing). | PASS | | **CA Cable Flex and Tensile Testing** | Verify the CA pigtail flex performance | CA Pigtail shall withstand 730 flex cycles (90° total) with no loss of performance. | PASS | | | Verify the CA pigtail tensile test | CA Pigtail shall withstand ≤ 4 lbf with no loss of performance. | PASS | | **CA design verification** | Verify the assembled CA meets its design intent | CA shall contain a coil attached to a cable, amplifier and a magnet within the coil for recharging the IPG battery. | PASS | | **CA has ESD protection verification** | Verify the CA meets its ESD and reliability requirements | CA electronics shall have a predicted reliability of at least 90% at 1 year. | PASS | PMA P250013 Summary of Safety and Effectiveness Data Page 16 of 69 {16} | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | **RCC Mechanical Performance Testing** | Verify the RCC maintains performance after exposure to storage temperature and humidity extremes. | RCC shall meet performance requirements at storage temperatures between -10°C to 55°C and ≤ 95% humidity (non-condensing) and no physical damage shall be observed. | PASS | | | Verify the RCC predicted reliability by conducting mean time to failure (MTTF) calculations | RCC shall have a predicted reliability of at least 90% at 1 year. | PASS | | **RCC and CA Electrical Safety Testing** | Verify the RCC and CA meet international standards for electrical safety | Meet the requirements for basic safety and essential performance per IEC/EN 60601-1-11. | PASS | | **Electromagnetic Compatibility (EMC) Testing** | Verify the RCC and CA meet international standards for emissions and immunity | Meets requirements of emissions and immunity per IEC 60601-1-2, Clause 7 & 8. | PASS | ### D. aura6000™ system Level Testing Table 7 presents high-level summary results of the aura6000™ system level testing, with information regarding the test, purpose, applicable acceptance criteria and results. Table 7. System Level Testing Summary | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | **IPG and Lead System Verification Testing** | Verify the IPG and lead repeated insertions performance | Lead proximal connector shall exhibit no mechanical detachment or damage due to the insertion into or removal from the IPG. Resistance shall be < 20 Ω; lead shall require an insertion and extraction force of < 10 N. | PASS | | | Verify the IPG and lead maximum extraction force | Lead shall exhibit maximum extraction force < 10 N. | PASS | | | Verify the IPG and lead maximum insertion force | Lead shall exhibit insertion force < 10 N. | PASS | | | Verify the IPG set screw secures lead | The torque wrench shall deliver 4 oz-in of torque and mates with the IPG set screw. | PASS | PMA P250013 Summary of Safety and Effectiveness Data Page 17 of 69 {17} | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | | Verify the lead retention when set screw engaged | Connector shall exhibit ≥ 10 N of force to extract the lead from the IPG, no damage or detachment, resistance shall be < 20 Ω. Per ISO 14708 (section 23.6), re-connection shall be possible without a degradation in performance. | PASS | | | Verify temperature rise of the IPG and lead while stimulating | IPG and lead electrode: The calculated CEM43 value ≤ 21 over 10 hour sleep session. | PASS | | **RCC and CA System Verification Testing** | Verify the RCC and CA connector | CA shall securely attach to the RCC with a locking connector | PASS | | | Verify the RCC and CA operating conditions (Temperature and Humidity) | RCC and CA shall endure operating conditions testing with no loss of performance. Functions at 5°C to 30°C and 15% to 85% humidity (non-condensing) and no physical damage observed. | PASS | | **IPG, RCC and CA Electrical Safety Testing** | Verify the aura6000™ system meets standards for system heating while charging IPG | Meets requirements of system heating while charging IPG per ISO 14708-3 Clause 17.1 and IEC 60601-1 Clause 11.1.1. | PASS | | **Torque Wrench and Suture Sleeve Mechanical Performance Testing** | Verify supplied torque wrench functionality | A torque wrench shall be provided with the IPG in order to provide a header/connector retention force of at least 10 N and the torque wrench shall have a torque limit of 4 oz-in ± 1 oz-in. | PASS | | **Suture Sleeve Verification Testing** | Verify suture sleeve functionality | Suture sleeve shall allow fixation of Lead body to fascia without having sutures tied directly to the lead body. | PASS | ### E. Biocompatibility The aura6000™ system, which includes the IPG Model 100.0100, Lead Models 300.0100 and 300.0200 (with implantable suture sleeve), CA Model 500.0300, and RCC Model 500.0100, has undergone biocompatibility and/or chemical characterization testing (Table 8). This testing and subsequent biological and toxicological risk assessments conducted for the device confirms compliance with the requirements of ISO 10993-1:2018, “Biological evaluation of medical devices. Part 1: Evaluation and testing within a risk management process” and the FDA Guidance document titled “Guidance for Industry and Food and Drug Administration Staff: Use of International Standard ISO 10993-1, Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing Within a Risk Management Process,” PMA P250013 Summary of Safety and Effectiveness Data Page 18 of 69 {18} issued on September 8, 2023, as well as ISO 14791:2019, “Medical Devices – Application of risk management to medical devices.” **Table 8. Summary of aura6000™ system Biocompatibility Evaluation** | Test | Device | Purpose | Results | | --- | --- | --- | --- | | **Cytotoxicity** ISO 10993-5 | - IPG - Lead - RCC - CA | Evaluate the devices for potential cytotoxic effects. | Pass, non-cytotoxic | | **Sensitization** ISO 10993-10 | - IPG - Lead - RCC - CA | Evaluate the devices for the potential to cause delayed dermal contact sensitization. | Pass, non-sensitizing | | **Irritation/ Intracutaneous Reactivity** ISO 10993-10 | - IPG - Lead - RCC - CA | Evaluate the devices for the potential to cause local dermal irritation. | Pass, non-irritant | | **Material Mediated Pyrogenicity** ISO 10993-11 | - IPG - Lead | Evaluate the devices for inducing a pyrogenic response. | Pass, non-pyrogenic | | **Acute Systemic Toxicity** ISO 10993-11 | - IPG - Lead | Evaluate the devices for inducing a systemic toxicity from acute exposure. | Pass, non-toxic | | **Genotoxicity** ISO 10993-3 | - IPG - Lead | Evaluate the devices for mutagenic potential. | Pass, non-mutagenic | | **ISO Chemical Characterization of Materials** ISO 10993-18 | - IPG - Lead | Chemical characterization of extractable and leachable chemicals associated with the device. | All test samples met the acceptance criteria with MOS>1 or exposure levels 50% of treated subjects were AHI responders (AHI < 20 and ≥ 50% reduction in AHI, Sher Criteria) • Demonstrate that > 50% of treated subjects | 46 | At 12 months, the AHI and ODI response rate was 32%, ESS score was -4.2 points (exceeding MCID). Subgroup analysis of baseline factors provided valuable insights for future patient selection. Device explant was performed in 5% of subjects (7/138). No UADEs or deaths. A total of 13 SAEs were deemed related, which | PMA P250013 Summary of Safety and Effectiveness Data Page 24 of 69 {24} | Document Number | Title | Study Type | Primary Endpoint | Sample Size | Conclusion | | --- | --- | --- | --- | --- | --- | | | | | achieve reduction in ODI ≥ 50% Secondary endpoints included QoL measurements | | all resolved without sequelae. Suspension of therapy for 1 week at 6 months and 2 weeks at 12 months did not result in significant changes to AHI or ODI. | | G140158 | THN Study #3 (THN3) | RCT study, LTFU up to 5 years | At Month 4: RCT Phase Demonstrate that Treatment is superior to Control in 1) AHI RR (AHI < 20 and ≥ 50% reduction in AHI, Sher criteria), and 2) ODI RR (≥ 25% reduction in ODI) At 11 months of therapy (Month 12 for Treatment and Month 15 for Control): non-RCT phase Proportion of subjects in both groups that experience clinically meaningful long-term improvements at Month 12/15 versus Baseline AHI (≥ 50% responder rate required); | 138 | This RCT demonstrated superiority of THN therapy over a control group that underwent implant but no THN therapy, over a 4-month randomization period, as indicated by significantly improved measures of sleep-disordered breathing, daytime somnolence and quality of life. The beneficial effects were sustained for up to 5 years. Surgical intervention for device explants or revisions was performed at a rate of 5% per year through the first 4 years and increased to 7.7% in the fifth year. No deaths and no UADE were observed during the trial, and SAEs related to device, implant or procedure occurred in 1.4% of subjects. The annual rate of device revision or replacement remained below 5% through the first four years, increasing to 7.7% in year five. In total, 22 subjects | PMA P250013 Summary of Safety and Effectiveness Data Page 25 of 69 {25} | Document Number | Title | Study Type | Primary Endpoint | Sample Size | Conclusion | | --- | --- | --- | --- | --- | --- | | | | | ODI (≥ 50% responder rate required). Secondary endpoints included QoL measurements | | underwent a device revision or replacement through Month 60. | | G200365 | OSPREY | Pivotal, RCT study | Primary efficacy endpoint is to demonstrate that the AHI responder rate of subjects with the device stimulation activated (Active Group) is statistically significantly higher than the AHI responder rate of subjects with the device stimulation not activated (Control Group) at M7 Secondary endpoints included ODI and QoL measurements | 104 | AHI Responder Rate (RR) in treatment group was statistically significantly greater than Control (58.2% vs 13.5% after 7 months), with the Active group AHI RR increasing to 64.6% after 13 months (12 months of treatment). All but 2 of the secondary endpoints found the Treatment superior to the Control. Surgical intervention for device explants or revisions was performed in 6% of Active subjects through 7 months (4/67). Procedure-related AEs observed in 41.3% of subjects. Through 7 months in the Active group, stimulation-related AEs observed in 19.4% of subjects and device-related AEs observed in 7.5% of subjects. No deaths and no UADEs were observed during the trial. | | Abbreviations, ESS: Epworth Sleepiness Scale, LTFU: long-term follow-up, MCID: minimal clinically important difference, AHI: apnea hypopnea index, ODI: oxygen desaturation index, RR: responder rate, QoL: quality of life, UADE: unanticipated adverse device event, | | | | | | PMA P250013 Summary of Safety and Effectiveness Data Page 26 of 69 {26} | Document Number | Title | Study Type | Primary Endpoint | Sample Size | Conclusion | | --- | --- | --- | --- | --- | --- | | RCT: randomized controlled trial, Sher criteria defined as a reduction in AHI of at least 50% and a final AHI of 20 or less | | | | | | ### A. Clinical Studies The THN1 Study (NCT01532180) was the first early feasibility study of the equivalent Legacy aura6000™ system. It was a single-center study conducted in Belgium, involving 14 subjects (14 implanted and 13 receiving stimulation therapy). The study demonstrated significant improvement and sustained effect in apnea hypopnea index (AHI) and oxygen desaturation index (ODI) over a 12-month period. At 12 months, the 13 subjects experienced a mean AHI reduction from 45.3 ± 17.6 events/hr at screening to 21.0 ± 16.5 events/hr, with a mean decrease of 24.2 ± 17.8 events/hr (53.6% improvement). Similarly, 10 subjects (76.9%) were found to be “responders” to the therapy at 12 months based on at least a 50% reduction in AHI. The safety profile did not show any unanticipated serious adverse events (SAEs), and all adverse events (AEs) were fully resolved without sequelae. The THN2 Study, (NCT01796925) was a larger, multi-center study with 46 patients, which enrolled subjects in the USA and Europe. Fifteen of the 43 completers (34.9%) met the Sher criteria for AHI response at 6 months, and 12 of 38 (31.6%) completers at 12 months. The ODI results closely mirrored those of AHI. At 3, 6, and 12 months, the mean ODI decreased by approximately 9 points from baseline. Across all time points, 39.5% at 6 months and 31.6% at 12 months met the ODI responder criteria. Therapy suspension for 1 week at 6 months and 2 weeks at 12 months did not result in significant changes to AHI and ODI. Daytime sleepiness symptoms, measured by Epworth Severity Scale (ESS), showed clinically significant improvement from baseline during the treatment period, as evidenced by the lowering of mean scores by 3.7, 3.8 and 4.2 points, at Month 3, 6 and 12, respectively, well exceeded the minimal clinically important difference (MCID) of 2. Over the 12 months follow-up, no unanticipated adverse device effects (UADEs) or deaths were reported and 10 SAEs related to the device were reported. All device-related SAEs required surgical intervention or inpatient hospitalization, and resolved without sequelae after intervention. The THN3 Study was a prospective, multi-center, randomized, controlled study. All subjects were implanted with the aura6000™ system and randomized to the Treatment (N=92) or Control group (N=46) in a 2:1 ratio. Stimulation therapy was turned ON at Month 1 in the treatment group, and at Month 4 in the control group. All subjects received 11 months of pHGNS therapy with follow-up at Months 12 and 15, for Treatment and Control groups, respectively. The trial demonstrated superiority of THN therapy versus the Control group during the 4 month randomization period, where the responder rates for both AHI (Sher criteria) and ODI were significantly improved. Refer to Table 12. PMA P250013 Summary of Safety and Effectiveness Data Page 27 of 69 {27} **Table 12: Co-Primary Effectiveness Endpoint – Treatment Response at Month 4, and Months 12/15 for THN3 Study** | Endpoint | Treatment n/N (%) | Control n/N (%) | Absolute Difference [Treatment-Control] RR (95% CI) | Standardized Mean Difference [Treatment-Control] (95% CI) | | --- | --- | --- | --- | --- | | M4 AHI RR | 46/88 (52.3%) | 9/46 (19.6%) | 32.7 (15.2, 49.0) | 0.725 (0.360, 1.163) | | M4 ODI RR | 55/85 (62.5%) | 19/46 (41.3%) | 21.2 (3.3, 38.1) | 0.434 (0.070, 0.843) | | Endpoint | M11 Therapy Treatment and Control groups combined n/N (%) | | Absolute Difference from Performance Goal of 50% (95% CI) | | | M12/15 AHI RR | 59/138 (42.5%) | | -7.5 (-16.0, 1.4) | - 0.151 (-0.330, 0.015) | | M12/15 ODI RR | 83/138 (60.4%) | | +10.4 (1.6, 18.8) | 0.214 (0.045, 0.402) | | Abbreviations: AHI = Apnea-hypopnea index; ODI = Oxygen desaturation index; RR = Responder rate. | | | | | The positive outcomes as assessed by AHI and ODI at Month 4 were maintained in available subjects through 5 years of follow up (Table 13). **Table 13. Change in AHI and ODI - Baseline to Month 60 Post-Implant for THN3 Study** | Variable | Baseline | Month 12/15 | Month 24 | Month 36 | Month 48 | Month 60 | | --- | --- | --- | --- | --- | --- | --- | | **AHI** | | | | | | | | n | 138 | 134 | 114 | 98 | 76 | 83 | | Mean (SD) | 37.9 (9.8) | 27.6 (21.1) | 25.4 (18.6) | 25.3 (20.1) | 26.0 (21.5) | 28.0 (20.7) | | **AHI Change from Baseline** | | | | | | | | n | - | 134 | 114 | 98 | 76 | 83 | | Mean (SD) | | -10.1 (21.7) | -12.6 (19.9) | -12.5 (19.3) | -11.7 (21.3) | -8.7 (21.4) | | p-value | | < 0.0001 | < 0.0001 | < 0.0001 | < 0.0001 | < 0.001 | | **ODI** | | | | | | | | n | 138 | 134 | 114 | 98 | 76 | 83 | | Mean (SD) | 37.3 (9.9) | 27.2 (20.7) | 26.6 (18.8) | 27.4 (21.1) | 29.5 (23.9) | 31.0 (22.0) | | **ODI Change from Baseline** | | | | | | | | n | - | 134 | 114 | 98 | 76 | 83 | | Mean (SD) | | -9.9 (20.7) | -10.9 (19.6) | -9.8 (19.9) | -7.5 (22.7) | -5.0 (21.8) | | p-value | | < 0.0001 | < 0.0001 | < 0.0001 | < 0.001 | < 0.05 | PMA P250013 Summary of Safety and Effectiveness Data Page 28 of 69 {28} Mean score difference from baseline at Month 4 for ESS, Functional Outcomes of Sleep Questionnaire (FOSQ), and EuroQol 5 Dimension (EQ-5D) questionnaires were all statistically significantly greater for the Treatment group versus Control group, thus fulfilling the secondary endpoint hypotheses (Table 14). **Table 14. Secondary Effectiveness Endpoints at Month 4: ESS, FOSQ and EQ-5D for THN3 Study** | Endpoint | Treatment Mean (SD) | Control Mean (SD) | p-value | | --- | --- | --- | --- | | ESS | -4.5 (4.2) | -1.1 (3.5) | < 0.0001 | | FOSQ | 2.5 (3.0) | 1.1 (3.2) | 0.0017 | | EQ-5D | 5.3 (13.4) | 0.6 (8.4) | 0.0246 | | Abbreviations: ESS = Epworth Sleepiness Scale; FOSQ = Functional outcome of sleep questionnaire; EQ-5D = EuroQoL 5 Dimension. | | | | Quality of life indices, including ESS, FOSQ, EQ-5D Visual Analogue Scale (VAS) and the Snore Outcomes Survey (SOS) were also assessed at Months 12/15, 24, 36, 48, and 60. Table 15 provides the differences at each follow-up visit compared to baseline. Across all follow-up visits, mean ESS, FOSQ, EQ-5D VAS and SOS values showed statistically significant improvements compared to baseline. These positive outcomes were sustained for up to 5 years post-implant in subjects who remained in the study. PMA P250013 Summary of Safety and Effectiveness Data Page 29 of 69 {29} **Table 15. Quality of Life Endpoints Month 12/15 through Month 60 for THN3 Study** | Variable | Baseline | Month 12/15 | Month 24 | Month 36 | Month 48 | Month 60 | | --- | --- | --- | --- | --- | --- | --- | | **ESS** | | | | | | | | n | 133 | | | | | | | Mean ± SD | 11.4 ± 4.8 | | | | | | | **ESS Change from Baseline** | | | | | | | | n | - | 130 | 111 | 100 | 80 | 84 | | Mean ± SD | | -4.8 ± 4.6 | -5.1 ± 4.8 | -5.3 ± 5.1 | -5.2 ± 5.2 | -5.0 ± 5.1 | | p-value | | < 0.0001 | < 0.0001 | < 0.0001 | < 0.0001 | < 0.0001 | | **FOSQ** | | | | | | | | n | 133 | | | | | | | Mean ± SD | 14.9 ± 3.2 | | | | | | | **FOSQ Change from Baseline** | | | | | | | | n | - | 130 | 112 | 100 | 80 | 85 | | Mean ± SD | | 3.1 ± 3.1 | 3.2 ± 3.3 | 3.5 ± 3.1 | 3.4 ± 3.2 | 3.5 ± 3.4 | | p-value | | < 0.0001 | < 0.0001 | < 0.0001 | < 0.0001 | < 0.0001 | | **EQ-5D** | | | | | | | | **VAS** | | | | | | | | n | 134 | | | | | | | Mean ± SD | 78.4 ± 14.8 | | | | | | | **EQ-5D VAS Change from Baseline** | | | | | | | | n | - | 131 | 112 | 101 | 80 | 86 | | Mean ± SD | | 4.3 ± 12.1 | 4.4 ± 12.4 | 5.2 ± 13.3 | 5.0 ± 16.0 | 5.8 ± 13.0 | | p-value | | 0.0001 | 0.0002 | 0.0002 | 0.0009 | 0.0001 | | **SOS** | | | | | | | | n | | 131 | | | | | | Mean ± SD | | 28.9 ± 18.8 | | | | | | **SOS Change from Baseline** | | | | | | | | n | - | 110 | 91 | 79 | 63 | 69 | | Mean ± SD | | 36.6 ± 21.1 | 33.4 ± 21.5 | 33.1 ± 21.6 | 33.0 ± 23.4 | 29.2 ± 22.4 | | p-value | | <0.0001 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Over the 11-month period, the majority of non-serious adverse events were classified as mild. Additionally, only two subjects (2 out of 138, 1.4%) experienced a serious adverse event. No deaths and no UADE were observed during the trial. Over the 12-month follow-up period, 2 out of 92 subjects (2.2%) required device revision or replacement within four months of implantation. The annual rate of device revision or replacement remained below 5% through the first four years, increasing to 7.7% in year five. In total, 22 subjects underwent a device revision or replacement through Month 60. The three studies demonstrated long-term effectiveness and acceptable risk of the aura6000™ system in treating moderate to severe OSA through five years. They also provided data to support improvements in device design and patient/physician training, and to help determine criteria for patient selection for the pivotal trial. PMA P250013 Summary of Safety and Effectiveness Data Page 30 of 69 {30} # **B. OSPREY Pivotal Study titled “Treating Obstructive Sleep APnea using TaRgetEd HYpoglossal Neurostimulation: A Safety and Efficacy Trial for aura6000™ system** # **i. Study Design** There were 107 subjects implanted with the investigational device between 24 FEB 2022 and 01 APR 2024, where 104 subjects were included in the Intent-to-Treat (ITT) Population. There were 23 investigational sites with subject enrollment. This study was a multi-center, open-label, prospective, randomized controlled trial using the aura6000™ system in adult patients with moderate to severe OSA who had failed or were unwilling to use PAP treatment. All subjects who signed the informed consent form (ICF) were screened for eligibility. If the subjects met all inclusion criteria and none of the exclusion criteria, they were qualified to be implanted with the aura6000™IPG and Lead. All implanted subjects were randomized between 7 to 20 days post-implant, when they returned for the post-surgical visit, but prior to the Month 1 (M1) office visit and polysomnography (PSG) assessment. A qualified vendor provided independent scoring of PSGs throughout the study, and during the randomized phase of the study, was blinded to treatment assignments. Randomization was 2:1 in favor of stimulation therapy (Treatment Group). There was no allowance for crossover between treatment arms before Month 7 (M7). Note, all subjects were excluded from use of PAP or surgical treatments after enrollment. The aura6000™ system can be adjusted to each subject’s unique needs by testing different stimulation amplitudes across individual electrode contacts. This process aimed to identify the optimal contact settings to maximize tidal airflow, oxygenation (O₂ saturation), and overall sleep quality. The most effective configuration for each subject was then selected based on these parameters. This programming was made for the Treatment Group after M1 when therapy was turned ON for this group. Titration PSGs were based on the study schedule and subject needs. # **ii. Inclusion and Exclusion Criteria** Subjects must have met all the following criteria to be considered for enrollment (Table 16). Table 16. Inclusion Criteria | Criteria Number | Inclusion Criteria | | --- | --- | | 1. | The patient is willing and capable of providing informed consent. | | 2. | The patient is at least 22 years of age. | | 3. | The patient is willing and capable of: • Using the remote control and charger to activate the therapy and charge the implant (assessed by the site), and • Completing all questionnaires. | | 4. | The patient is willing and capable of returning for all follow-up evaluations and sleep studies for the duration of the study. | PMA P250013 Summary of Safety and Effectiveness Data Page 31 of 69 {31} | Criteria Number | Inclusion Criteria | | --- | --- | | 5. | The patient has documented diagnosis of moderate to severe OSA with an AHI of at least 15 using the AASM 2007 guideline for scoring hypopneas based on a nasal pressure drop of 30% or greater and a desaturation of >4%. | | 6. | The patient declines to use or does not tolerate PAP therapy. | | 7. | The patient expresses no difficulty with sleeping in unfamiliar environments and can do so without the use of drugs or medications. | Subjects who met any exclusion criteria were not eligible to be enrolled in the study (Table 17). **Table 17. Exclusion Criteria** | Criteria Number | Exclusion Criteria | | --- | --- | | 1. | The patient is implanted with another active implantable device that could experience an unintended interaction with the aura6000™ system. | | 2. | The patient is enrolled in another clinical study that has not reached conclusion or may confound the endpoint of this study. | | 3. | The patient is dependent on or frequently taking medications (such as opioids, narcotics, or stimulants) that significantly alter consciousness, the pattern of respiration, sleep architecture, or with known effect on sleep-wake function or alertness. | | 4. | The patient has difficulty falling asleep and/or uses a hypnotic for insomnia more than twice a month. | | 5. | The patient has moderate to severe (or poorly controlled) respiratory disease (e.g. COPD such as emphysema, TB, chest wall disease, uncontrolled asthma, allergic rhinitis, etc.) or is on supplemental oxygen therapy for any reason to control the respiratory disease. | | 6. | The patient has one of the following: moderate to severe heart failure, in the assessment of the investigator, [NOTE: NYHA Class II or above], or a history of persistent atrial fibrillation, unstable angina, recent history of MI (<6m), severe cardiac arrhythmias, or uncontrolled systemic or pulmonary hypertension. | | 7. | The patient has neurological, neuromuscular, or neurodegenerative disorders (e.g. transient ischemic attack (TIA), cerebrovascular accident (CVA), Parkinson's, multiple sclerosis (MS), muscular dystrophy (MD), epilepsy, diagnosed memory dysfunction, etc.). | | 8. | The patient has other sleep disorders that, in the opinion of the Investigator, could confound functional assessment of sleepiness (e.g., narcolepsy, insomnia, etc.) or sleep movement disorders (e.g. Restless Leg Syndrome (RLS), Periodic Limb Movement (PLM) disorder) that may cause sleep disturbances unrelated to OSA. | | 9. | The patient has an active psychiatric condition that, in the opinion of the investigator, might interfere with the patient's compliance with the protocol, | PMA P250013 Summary of Safety and Effectiveness Data Page 32 of 69 {32} | Criteria Number | Exclusion Criteria | | --- | --- | | | or affect endpoints' assessment (e.g. depression, schizophrenia, bipolar disorder, etc.). | | 10. | The patient has an active systemic infection. | | 11 | The patient has been admitted to rehabilitation for treatment of alcohol, tobacco, or recreational drug use within the last 12 months and/or has a history of habitual binge drinking. Must also be willing to refrain from alcohol use on the day of ALL PSGs. | | 12. | The patient is unwilling or unable to refrain from other OSA treatments including PAP, oral appliances, surgery, or medications, from enrollment through the completion of the study | | 13. | The patient has sleep hygiene behavior(s) that would substantially interfere with the study or its outcome assessment (e.g., shift work, sleeps less than 5 hours a night, psychophysiological insomnia, etc.). | | 14. | The patient has a body mass index (BMI) > 35 kg/m^{2}. | | 15 | The patient exhibits clinical evidence of renal insufficiency, acute or chronic renal failure, or undergoing or expected to undergo dialysis in the future. | | 16. | The patient has a condition likely to require future MRI, diathermy or other procedure producing strong radio frequency (RF) fields. | | 17. | The patient is pregnant or planning to become pregnant between consent and the final Month 13 (M13) visit, must also be willing to use a contraception method during this time (pre-menopausal women only). | | 18. | The patient has another reason the Investigator feels (s)he is a poor candidate for participation in the study (e.g., prior radiation therapy for cancer treatment, pre- existing hypoglossal nerve damage, various palsies, cranio-facial or bony trauma, etc.). | | 19. | The patient requires the use of aspirin, non-steroidal anti-inflammatory drugs (NSAIDS) or anti-coagulant medications that cannot be safely stopped at least 3-7 days prior to the scheduled implant per the surgeon's clinical standard of care. Acetaminophen is permitted if needed. | | 20. | The patient has conditions causing chronic pain that may affect the subject's ability to sleep comfortably in the sleep lab (e.g. herniated discs, degenerative disc disease, sciatic nerve pain, etc.). | | 21. | The patient whose upper airway exam has a palatine or lingual tonsil grading system of 3 or 4, or HGN palsy. | | 22. | The patient has obstructive upper airway lesions (e.g. tumors, polyps, etc.), or severe septal deviation. | | 23. | The patient exhibits evidence of Cheyne-Stokes or periodic breathing. | | 24. | The patient has been diagnosed with central sleep apnea per the International Classification of Sleep Disorders 3^{rd} Edition (ICSD-3) definition. | | 25. | Inability to obtain a repeatable AHI value (i.e., high variability in AHI >20) between screening home sleep tests (HSTs). | PMA P250013 Summary of Safety and Effectiveness Data Page 33 of 69 {33} | Criteria Number | Exclusion Criteria | | --- | --- | | 26. | The Subject meets one or more of the following sleep study criteria as assessed by the Baseline PSG: a. An AHI < 15 or ≥ 65 b. Apnea Index (AI) >30 events per hour c. >25% mixed or central apnea events as a proportion of the sum of apnea and hypopnea events per hour d. Positional OSA as defined by non-supine AHI <5 when sufficient non supine sleep is available to make this judgement e. Predominantly rapid eye movement (REM) OSA (ratio between the AHI in REM and AHI in non-rapid eye movement (NREM) >2) f. Indication of a sleep disorder or poor sleep hygiene that could confound functional assessments of sleepiness such as poor sleep efficiency in the opinion of the investigator. | ### iii. **Follow-Up Schedule** All subjects in the OSPREY Study were scheduled for follow-up examinations. Data collection at specified time points was based on evaluating safety and effectiveness. After successful screening and collection of baseline data including PSG tests, subjects were implanted with the aura6000™ system. Thereafter, between Day 7 and Day 20 subjects were randomized to treatment group. In parallel with the M1 in-office visit, therapy initiation (device activation) commenced during the required PSG test for the Treatment group only. Regular follow-up in-office visits occurred at 2, 3, 4, 5, 6, 7, 9, 11, and 13 months for the Treatment group. Additional PSG studies were required at 3, 6, and 7 months and as needed at 2, 4, and 5 months for the Treatment group. The Control group had regular follow-up in-office visits at 3, 5 and 7 months, and regularly scheduled phone calls at 2, 4, and 6 months during the RCT phase. Following the M7+1 day visit, the Control group had therapy initiated and followed the same initial schedule as the Active group. Primary evaluation of safety and effectiveness results occurred at M7 visit. The following schedule of events is provided as a summary of activities and time points in the OSPREY Study through M13 (**Table 18**) PMA P250013 Summary of Safety and Effectiveness Data Page 34 of 69 {34} **Table 18. OSPREY Study Follow-Up Schedule** | Time and Effort | All Groups | Active Group | | --- | --- | --- | | Screening through Implant | Randomization | Randomization (RCT) Phase - Primary Treatment Comparison | Post-Randomization Phase - All Groups Treatment | | Screening Visit(s) | Baseline | Implant | Randomize | Month 1 Active | Month 2 Active | Month 3 Active | Month 3+1D Active | Month 4 Active | Month 5 Active | Month 6 Active | Month 7 Active Primary Endpoint | Month 8 Active | Month 9 Active | Month 10 Active | Month 11 Active | Month 12 Active | Month 13 Active Exit PSG | | Visit Number | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | | Target Follow-up Post Implant / Window | ^Up to 90 days prior to Consent | Up to Implant date | Day 0 | Day 7 - 20 | D 21-45 | D 46-75 | D 76-105 | 1 D following M3 | D 106-135 | D 136-165 | D 166-195 | D 196-225 | D 226-255 | D 256-285 | D 286-315 | D 316-345 | D 346-375 | D 376-405 | | Informed Consent/HIPAA | x | | | | | | | | | | | | | | | | | | | Inclusion/ Exclusion Criteria Review | x | | x | | | | | | | | | | | | | | | | | Subject Demographics & Medical History | x | | | | | | | | | | | | | | | | | | | Surgical Consultation | x | | | | | | | | | | | | | | | | | | | Upper Airway Exam | x | | | | | | | | | | | | | | | | | | | HGN/Tongue Function Assessment | x | | | | x | x | x | | x | x | x | x | | x | | x | | x | | Physical Exam (neck circum./healthy lifestyle review) | x | | | x | x | x | x | | x | x | x | x | | x | | x | | x | | Vital Signs (HT/WT/HR/BP) | x | x | | x | x | x | x | | x | x | x | x | | x | | x | | x | | Home Sleep Tests (2 HSTs up to a 3 night-time period) | x | | | | | | | | | | | | | | | | | | | PSG R1 (baseline to be done after HSTs) | | x | | | x | x* | x | | x* | x* | x | x | x* | x* | x* | x | x* | x | | PSG R2 | | | | | | | | x | | | | | | | | | | | | Urine Pregnancy Test | x* | | x* | | | | | | | | | | | | | | | | | Implant Surgery | | | x | | | | | | | | | | | | | | | | | Wound Check | | | | x | | | | | | | | | | | | | | | | Randomization in EDC | | | | x | | | | | | | | | | | | | | | | ESS | | x | | | | | | | | | | x | | | | | | x | | FOSQ | | x | | | | | | | | | | x | | | | | | x | | EQ-5D-5L | | x | | | | | | | | | | x | | | | | | x | | SF36 | | x | | | | | | | | | | x | | | | | | x | | Clinical Global Impression S (CGI S) | | x | | | | | | | | | | | | | | | | | | Clinical Global Impression I (CGI I) | | | | | | | | | | | | x | | | | | | x | | PROMIS SRI SDI | | x | | | | | | | | | | x | | | | | | x | | Therapy Satisfaction Questionnaire | | | | | | | | | | | | x | | | | | | x | | Therapy Initiation | | | | | x | | | | | | | | | | | | | | | Subject Training | | | | | x | x* | x* | x* | x* | x* | x* | x* | x* | x* | x* | x* | x* | x* | | Device Interrogation / sensory testing / Usage log download | | | | | x | x | x | | x | x | x | x | x* | x | x* | x | x* | x | | Phone Call | | | | | | | | | | | | | x | | x | | x | | | Medication Review | x | | x | x | x | x | x | | x | x | x | x | x | x | x | x | x | x | | Adverse event Review | x | | x | x | x | x | x | | x | x | x | x | x | x | x | x | x | x | | Overall Subject Satisfaction Questionnaire | | | | | | | | | | | | | | | | | | x | | Study Completion/Termination/Exit | | | | | | | | | | | | | | | | | | x | | x* = only if indicated | | | | | | | | | | | | | | | | | | | | ^consent MUST occur before any solely study related activities | | | | | | | | | | | | | | | | | | | PMA P250013 Summary of Safety and Effectiveness Data Page 35 of 69 {35} | Time and Effort | All Groups | | | | Control Group | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Screening through Implant | | | Randomization | Randomization (RCT) Phase - Primary Treatment Comparison | | | | | | | Post-Randomization Phase - All Groups Treatment | | | | | | | | | | Screening Visit(s) | Baseline | Implant | Randomize | Month 1 Control | Month 2 Control | Month 3 Control | Month 4 Control | Month 5 Control | Month 6 Control | Month 7 Control Primary Endpoint | Month 7+1D Control | Month 8 Control | Month 9 Control | Month 9+1D Control | Month 10 Control | Month 11 Control | Month 12 Control | Month 13 Control Exit PSG | | Visit Number | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 11 | 12 | 13 | 13 | 14 | 15 | 16 | 17 | | Target Follow-up Post Implant / Window | *Up to 90 days prior to Consent | Up to Implant date | Day 0 | Day 7 - 20 | D 21-45… --- **Source:** [https://fda-staging.innolitics.com/device/P250013](https://fda-staging.innolitics.com/device/P250013) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. 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