A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight (TRIUMPH-2)

• ClinicalTrials.gov Identifier: NCT05929079
• Recruitment Status: Recruiting
• First Posted: July 3, 2023
• Last Update Posted: April 18, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: June 26, 2023
• First Posted Date: July 3, 2023
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: July 11, 2023
• Estimated Primary Completion Date: May 3, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 26, 2023)

• Percent Change from Baseline in Body Weight [ Time Frame: Baseline, Week 80 ]
• Change from Baseline in Apnea-Hypopnea Index (AHI) for GSA2 Subset [ Time Frame: Baseline, Week 80 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 26, 2023)

• Change from Baseline in Body Mass Index (BMI) [ Time Frame: Baseline, Week 80 ]
• Change from Baseline in Waist Circumference [ Time Frame: Baseline, Week 80 ]
• Change from Baseline in Systolic Blood Pressure (SBP) [ Time Frame: Baseline, Week 80 ]
• Change from Baseline in Diastolic Blood Pressure (DBP) [ Time Frame: Baseline, Week 80 ]
• Percent Change from Baseline in Total Cholesterol [ Time Frame: Baseline, Week 80 ]
• Percent Change from Baseline in Triglycerides [ Time Frame: Baseline, Week 80 ]
• Change from Baseline in Hemoglobin (A1c) HbA1c % [ Time Frame: Baseline, Week 80 ]
• Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score [ Time Frame: Baseline, Week 80 ]
• Change from Baseline in Fasting Glucose [ Time Frame: Baseline, Week 80 ]
• Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) [ Time Frame: Baseline through Week 80 ]
  AUC is presented as a single average measure of AUC across the study duration.
• Percent Change from Baseline in Apnea-Hypopnea Index (AHI) for GSA2 Subset [ Time Frame: Baseline, Week 80 ]
• A Hierarchical Combination of Functional Outcomes of Sleep Questionnaire (FOSQ) 10 score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score for GSA2 Subset [ Time Frame: Baseline to Week 80 ]
  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 component.
• Percentage of Participants with ≥50% AHI Reduction from Baseline for GSA2 Subset [ Time Frame: Baseline to Week 80 ]
• Percentage of Participants with AHI <5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10 for GSA2 Subset [ Time Frame: Week 80 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight
• Official Title: A Master Protocol to Investigate the Efficacy and Safety of LY3437943 Once Weekly in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight: A Randomized Double-Blind, Placebo-Controlled Trial
• Brief Summary: The purpose of this study is to is to evaluate the efficacy and safety of retatrutide in participants with type 2 diabetes in participants who have obesity or overweight (J1I-MC-GZBK master protocol) including a subset of participants who have obstructive sleep apnea (OSA) (J1I-MC-GSA2). The study will last about 89 weeks and will include up to 24 visits.
• 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

• Type 2 Diabetes
• Obesity
• Overweight
• Obstructive Sleep Apnea

Intervention

• Drug: Retatrutide
  Administered SC
  Other Name: LY3437943
• Drug: Placebo
  Administered SC

Study Arms

• Experimental: Retatrutide Dose 1
  Participants will receive retatrutide subcutaneously (SC).
  Intervention: Drug: Retatrutide
• Experimental: Retatrutide Dose 2
  Participants will receive retatrutide SC.
  Intervention: Drug: Retatrutide
• Experimental: Retatrutide Dose 3
  Participants will receive retatrutide SC.
  Intervention: Drug: Retatrutide
• Placebo Comparator: Placebo
  Participants will receive placebo.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 26, 2023): 1000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2026
• Estimated Primary Completion Date: May 3, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have a body mass index (BMI) greater than or equal to 27.0 kilogram/square meter (kg/m ²)
• Have Type 2 Diabetes (T2D)
• Are on stable treatment for T2D for at least 90 days
• Have a history of at least one unsuccessful dietary effort to lose body weight.

GSA2 Inclusion Criteria

• Previously diagnosed with OSA
• Have AHI ≥15 on polysomnography at screening (definition of moderate-to-severe OSA)
• For participants not on positive airway pressure (PAP) therapy: unable or unwilling to use PAP therapy and have not used PAP for at least 4 weeks prior to screening.
• If on PAP therapy, have been on PAP therapy for at least 3 consecutive months prior to screening, and willing to temporarily stop using PAP therapy for approximately 7 days prior to each of the sleep study (PSG) visits.

Exclusion Criteria:

• Have a self-reported or documented change in body weight >5 kg (11 pounds) within 90 days.
• Have taken weight loss drugs, including over-the-counter medications, within 90 days prior to screening.
• Have a prior or planned surgical treatment for obesity.
• Have Type 1 diabetes
• Have a family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
• Have had pancreatitis

GSA2 Exclusion Criteria

• Use stimulants (for example, modafinil, armodafinil, solriamfetol, pitolisant, amphetamine) less than 3 months prior to screening.
• Use hypnotics, mirtazapine, opioids, trazodone, and zonisamide less than 3 months prior to screening.
• Use a dental appliance or other device to treat OSA other than PAP therapy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Argentina, Australia, Brazil, India, Mexico, Romania, Spain, Taiwan, United States
• Removed Location Countries: China, Korea, Republic of

Administrative Information

• NCT Number: NCT05929079
• Other Study ID Numbers: 18558; J1I-MC-GZBK ( Other Identifier: Master Protocol Eli Lilly and Company ); J1I-MC-GSA2 ( Other Identifier: ISA Eli Lilly and Company ); 2023-503658-11-00 ( Other Identifier: EU Trial 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 participant 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: a 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 1, 2024