A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight (SURMOUNT-1)

• ClinicalTrials.gov Identifier: NCT04184622
• Recruitment Status: Active, not recruiting
• First Posted: December 3, 2019
• Results First Posted: April 24, 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: December 2, 2019
• First Posted Date: December 3, 2019
• Results First Submitted Date: March 30, 2023
• Results First Posted Date: April 24, 2023
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: December 4, 2019
• Actual Primary Completion Date: April 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 30, 2023)

• Percent Change From Baseline in Body Weight [ Time Frame: Baseline, Week 72 ]
  Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model.
• Percentage of Participants Who Achieve ≥5% Body Weight Reduction [ Time Frame: Week 72 ]
  Percentage of participants who achieve ≥5% body weight reduction.

Original Primary Outcome Measures (submitted: December 2, 2019)

• Percent Change from Baseline in Body Weight [ Time Frame: Baseline, Week 72 ]
  Percent Change from Baseline in Body Weight
• Percentage of Participants who Achieve ≥5% Body Weight Reduction [ Time Frame: Week 72 ]
  Percentage of Participants who Achieve ≥5% Body Weight Reduction

Current Secondary Outcome Measures (submitted: March 30, 2023)

• Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) [ Time Frame: Baseline, Week 20 ]
  LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model.
• Percent Change From Baseline in Body Weight [ Time Frame: Baseline, Week 176 ]
  Percent Change from Baseline in Body Weight.
• Percentage of Participants Who Achieve ≥10% Body Weight Reduction [ Time Frame: Week 72 ]
  Percentage of Participants who Achieve ≥10% Body Weight Reduction
• Percentage of Participants Who Achieve ≥15% Body Weight Reduction [ Time Frame: Week 72 ]
  Percentage of participants who achieve ≥15% body weight reduction.
• Percentage of Participants Who Achieve ≥5% Body Weight Reduction [ Time Frame: Week 176 ]
  Percentage of Participants who Achieve ≥5% Body Weight Reduction.
• Percentage of Participants Who Achieve ≥20% Body Weight Reduction [ Time Frame: Week 72 ]
  Percentage of participants who achieve ≥20% body weight reduction.
• Change From Baseline in Waist Circumference [ Time Frame: Baseline, Week 72 ]
  LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model.
• Change From Baseline in Body Mass Index (BMI) [ Time Frame: Baseline, Week 72 ]
  LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model.
• Change From Baseline in Fasting Glucose [ Time Frame: Baseline, Week 72 ]
  LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model.
• Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) [ Time Frame: Baseline, Week 72 ]
  Fasting Insulin is a test used to measure the amount of insulin in the body. Results are reported as model-based estimates and SE from MMRM analysis using log transformation.
• Time to Onset of Type 2 Diabetes [ Time Frame: Baseline through Week 176 ]
  Time to Onset of Type 2 Diabetes
• Change From Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, Week 72 ]
  HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model.
• Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) [ Time Frame: Baseline, Week 72 ]
  Percent change from baseline in triglycerides are reported as model-based estimate and Standard Error (SE) from MMRM analysis using log transformation.
• Percent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) [ Time Frame: Baseline, Week 72 ]
  Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
• Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) [ Time Frame: Baseline, Week 72 ]
  Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
• Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) [ Time Frame: Baseline, Week 72 ]
  Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
• Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) [ Time Frame: Baseline, Week 72 ]
  Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
• Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) [ Time Frame: Baseline, Week 72 ]
  Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
• Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) [ Time Frame: Baseline, Week 72 ]
  LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model.
• Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) [ Time Frame: Baseline, Week 72 ]
  LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model.
• Change From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) [ Time Frame: Baseline, Week 72 ]
  The SF-36v2 acute, 1-week recall version is a 36-item, generic, patient-administered measure designed to assess the following 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" while the remaining domains assess functioning "in the past week." Each domain is scored individually and information from these 8 domains are further aggregated into 2 health-component summary scores: Physical-Component Summary and Mental-Component Summary. Items are answered on Likert scales of varying lengths (3-, 5-, or 6- point scales).The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health.
• Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 [ Time Frame: Baseline, Week 72 ]
  The IWQOL-Lite-CT is a 20-item, obesity-specific PRO instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items), and psychosocial (13 items). A 5-item subset of the physical domain, the physical-function composite is also supported. Items in the physical-function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better quality of life.
• Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide [ Time Frame: Week 8, 16, and 36, at 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose ]
  PK: Steady State AUC of Tirzepatide. each participant will be assigned via the Interactive Web Response System (IWRS) to one of the sampling PK time windows of 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose.

Original Secondary Outcome Measures (submitted: December 2, 2019)

• Change from Baseline in Body Weight [ Time Frame: Baseline, Week 20 ]
  Change from Baseline in Body Weight
• Percent Change from Baseline in Body Weight [ Time Frame: Baseline, Week 176 ]
  Percent Change from Baseline in Body Weight
• Percentage of Participants who Achieve ≥10% Body Weight Reduction [ Time Frame: Week 72 ]
  Percentage of Participants who Achieve ≥10% Body Weight Reduction
• Percentage of Participants who Achieve ≥15% Body Weight Reduction [ Time Frame: Week 72 ]
  Percentage of Participants who Achieve ≥15% Body Weight Reduction
• Percentage of Participants who Achieve ≥5% Body Weight Reduction [ Time Frame: Week 176 ]
  Percentage of Participants who Achieve ≥5% Body Weight Reduction
• Change from Baseline in Waist Circumference [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in Waist Circumference
• Change from Baseline in Body Mass Index (BMI) [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in BMI
• Change from Baseline in Fasting Glucose [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in Fasting Glucose
• Change from Baseline in Fasting Insulin [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in Fasting Insulin
• Time to Onset of Type 2 Diabetes [ Time Frame: Baseline through Week 176 ]
  Time to Onset of Type 2 Diabetes
• Change from Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in HbA1c
• Change from Baseline in Triglycerides [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in Triglycerides
• Change from Baseline in Low-Density Lipoprotein (LDL) Cholesterol [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in LDL Cholesterol
• Change from Baseline in Total Cholesterol [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in Total Cholesterol
• Change from Baseline in High-Density Lipoprotein (HDL) Cholesterol [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in HDL Cholesterol
• Change from Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in VLDL Cholesterol
• Change from Baseline in Free Fatty Acids [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in Free Fatty Acids
• Change from Baseline in Systolic Blood Pressure [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in Systolic Blood Pressure
• Change from Baseline in Diastolic Blood Pressure [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in Diastolic Blood Pressure
• Change from Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in SF-36v2 Acute Form Physical Functioning Domain Score
• Change from Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score [ Time Frame: Baseline, Week 72 ]
  Change from Baseline in IWQOL-Lite-CT Physical Function Composite Score
• Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide [ Time Frame: Baseline through Week 72 ]
  PK: Steady State AUC of Tirzepatide

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

Descriptive Information

• Brief Title: A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight
• Official Title: Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight- Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)
• Brief Summary: This is a study of tirzepatide in participants with overweight and obesity. The main purpose is to learn more about how tirzepatide affects body weight. The study has two phases: A main phase and an extension phase. The main phase of the study will last 72 weeks. Participants with prediabetes will continue in the extension for another 2 years.
• 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

• Overweight
• Obesity

Intervention

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

Study Arms

• Experimental: 5 mg Tirzepatide
  5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
  Intervention: Drug: Tirzepatide
• Experimental: 10 mg Tirzepatide
  10 mg tirzepatide administered SC once a week.
  Intervention: Drug: Tirzepatide
• Experimental: 15 mg Tirzepatide
  15 mg tirzepatide administered SC once a week.
  Intervention: Drug: Tirzepatide
• Placebo Comparator: Placebo
  Placebo administered SC once a week.
  Intervention: Drug: Placebo

• Publications *: Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 2, 2021): 2539
• Original Estimated Enrollment (submitted: December 2, 2019): 2400
• Estimated Study Completion Date: July 8, 2024
• Actual Primary Completion Date: April 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Body mass Index (BMI) ≥30 kilograms per square meter (kg/m²), or ≥27 kg/m² and previous diagnosis with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease
• History of at least one unsuccessful dietary effort to lose body weight

Exclusion Criteria:

• Diabetes mellitus
• Change in body weight greater than 5 kg within 3 months prior to starting study
• Obesity induced by other endocrinologic disorders or monogenetic or syndromic forms of obesity
• History of pancreatitis
• Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
• History of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder within the last 2 years
• Any lifetime history of a suicide attempt

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: Argentina, Brazil, China, India, Japan, Mexico, Puerto Rico, Russian Federation, Taiwan, United States

Administrative Information

• NCT Number: NCT04184622
• Other Study ID Numbers: 17244; I8F-MC-GPHK ( Other Identifier: Eli Lilly and Company )
• 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 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