Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea (SURMOUNT-OSA)

• ClinicalTrials.gov Identifier: NCT05412004
• Recruitment Status: Completed
• First Posted: June 9, 2022
• Last Update Posted: April 19, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: May 25, 2022
• First Posted Date: June 9, 2022
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: June 21, 2022
• Actual Primary Completion Date: March 12, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 23, 2023): Change from Baseline in Apnea-Hypopnea Index (AHI) [ Time Frame: Baseline, Week 52 ]
• Original Primary Outcome Measures (submitted: June 8, 2022): Percent Change from Baseline in Apnea-Hypopnea Index (AHI) [ Time Frame: Baseline, Week 52 ]

Current Secondary Outcome Measures (submitted: June 23, 2023)

• A Hierarchical Combination of Functional Outcomes of Sleep Questionnaire (FOSQ) 10 Score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score [ Time Frame: Baseline (Week 0) to Study Completion (Estimated Up to 52 Weeks) ]
  A hierarchical combination of change from baseline in the FOSQ 10 score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score will be assessed by the win ratio. The reported unit will be the total "wins" for each treatment group from performing a hierarchical comparison of the components.
• Percent Change from Baseline in Apnea-Hypopnea Index (AHI) [ Time Frame: Baseline, Week 52 ]
• Percentage of Participants with ≥50% AHI Reduction from Baseline [ Time Frame: Week 52 ]
• Percentage of Participants with AHI <5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10 [ Time Frame: Week 52 ]
• Percent Change from Baseline in Body Weight [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in Systolic Blood Pressure (SBP) [ Time Frame: Baseline, Week 48 ]
• Change from Baseline in High Sensitivity C reactive Protein (hsCRP) Concentration [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% min/hour) [ Time Frame: Baseline, Week 52 ]

Original Secondary Outcome Measures (submitted: June 8, 2022)

• A Hierarchical Combination of Functional Outcomes of Sleep Questionnaire (FOSQ) 10 Score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score [ Time Frame: Baseline (Week 0) to Study Completion (Estimated Up to 52 Weeks) ]
  A hierarchical combination of change from baseline in the FOSQ 10 score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score will be assessed by the win ratio. The reported unit will be the total "wins" for each treatment group from performing a hierarchical comparison of the components.
• Percentage of Participants with ≥50% AHI Reduction from Baseline [ Time Frame: Week 52 ]
• Percentage of Participants with AHI <5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10 [ Time Frame: Week 52 ]
• Percent Change from Baseline in Body Weight [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in Systolic Blood Pressure (SBP) [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in High Sensitivity C reactive Protein (hsCRP) Concentration [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% min/hour) [ Time Frame: Baseline, Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea
• Official Title: A Master Protocol to Investigate the Efficacy and Safety of Tirzepatide Once Weekly in Participants Who Have Obstructive Sleep Apnea and Obesity: A Randomized, Double-Blind, Placebo-Controlled Trial
• Brief Summary: The purpose of this study is to evaluate the effect and safety of tirzepatide in participants with obstructive sleep apnea and obesity who are both unwilling or unable to use Positive Airway Pressure (PAP) therapy in GPI1 and those who are and plan to stay on PAP therapy in GPI2.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Sleep Apnea
• Obesity

Intervention

• Drug: Tirzepatide
  Administered SC
  Other Name: LY3298176
• Drug: Placebo
  Administered SC

Study Arms

• Experimental: Tirzepatide Maximum Tolerated Dose

  Participants will receive a low dose and then increase to a maximum tolerated dose 1 or dose 2 subcutaneously (SC).

  GPI1: Participants are unwilling or unable to use PAP therapy.

  GPI2: Participants are on PAP therapy.

  Intervention: Drug: Tirzepatide
• Placebo Comparator: Placebo

  Participants will receive placebo SC

  GPI1: Participants are unwilling or unable to use PAP therapy.

  GPI2: Participants are on PAP therapy.

  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 20, 2023): 469
• Original Estimated Enrollment (submitted: June 8, 2022): 412
• Actual Study Completion Date: March 29, 2024
• Actual Primary Completion Date: March 12, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

For GPI1 Participants:

- Participants who are unable or unwilling to use PAP therapy. Participants must not have used PAP for at least 4 weeks prior to screening.

For GPI2 Participants:

- Have been on PAP therapy for at least 3 consecutive months prior to screening and plan to continue PAP therapy during the study

For Both GPI1 and GPI2 Participants:

• Have an AHI ≥15 on PSG as part of the trial at screening
• Have a body mass index (BMI) ≥30 kilogram/square meter (kg/m²)
• Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight

Exclusion Criteria:

For GPI2 Participants:

• Have personal or job-related responsibilities, or in the opinion of the investigator have any situation, that would make it unsafe to stop PAP therapy for 7 days prior to PSG testing during the course of the study
• Are unwilling to stop PAP therapy for 7 days prior to polysomnography (PSG) testing during the course of the study

For GPI1 and GPI2 Participants:

• Female participants must not be pregnant, intending to be pregnant, breastfeeding, or intending to breastfeed.
• Have type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), history of ketoacidosis, or hyperosmolar state/coma.
• Have HbA1c ≥ 6.5% (≥ 48 mmol/mol) at baseline
• Any previous or planned surgery for sleep apnea or major ear, nose or throat surgery, including tonsillectomy and adenoidectomy that still may affect breathing at time of baseline
• Have significant craniofacial abnormalities that may affect breathing at baseline
• Have diagnosis of Central or Mixed Sleep Apnea with % of mixed or central apneas/hypopneas ≥50%, or diagnosis of Cheyne Stokes Respiration
• Diagnosis of Obesity Hypoventilation Syndrome or daytime hypercapnia.
• Active device treatment of OSA other than PAP therapy (for example, dental appliance), or other treatment, that in the opinion of the investigator, may interfere with study outcomes, unless willing to stop treatment at baseline and throughout the study.
• Respiratory and neuromuscular diseases that could interfere with the results of the trial in the opinion of the investigator.
• Have a self-reported change in body weight >5 kg within 3 months prior to screening
• Have a prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty if performed more than 1 year prior to screening)
• Have or plan to have endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months (for example, mucosal ablation, gastric artery embolization, intragastric balloon, and duodenal-jejunal bypass sleeve)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, China, Czechia, Germany, Japan, Mexico, Puerto Rico, Taiwan, United States

Administrative Information

• NCT Number: NCT05412004
• Other Study ID Numbers: 18357; I8F-MC-GPIF ( Other Identifier: Eli Lilly and Company ); I8F-MC-GPI1 ( Other Identifier: Eli Lilly and Company ); I8F-MC-GPI2 ( Other Identifier: Eli Lilly and Company ); 2021-004552-41 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: http://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: April 2024