A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight (SURMOUNT-2)

• ClinicalTrials.gov Identifier: NCT04657003
• Recruitment Status: Active, not recruiting
• First Posted: December 7, 2020
• Last Update Posted: April 19, 2022
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: December 1, 2020
• First Posted Date: December 7, 2020
• Last Update Posted Date: April 19, 2022
• Actual Study Start Date: March 29, 2021
• Estimated Primary Completion Date: March 20, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 1, 2020)

• Percent Change from Randomization in Body Weight [ Time Frame: Randomization, 72 Weeks ]
  Percent Change from randomization in body weight
• Percentage of Participants Who Achieve ≥5% Body Weight Reduction from Randomization [ Time Frame: 72 Weeks ]
  Percentage of participants who achieve ≥5% body weight reduction from randomization

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 1, 2020)

• Percentage of Participants Who Achieve ≥10% Body Weight Reduction from Randomization [ Time Frame: 72 Weeks ]
  Percentage of participants who achieve ≥10% body weight reduction from randomization
• Percentage of Participants Who Achieve ≥15% Body Weight Reduction from Baseline [ Time Frame: 72 Weeks ]
  Percentage of participants who achieve ≥15% body weight reduction from randomization
• Change from Randomization in Absolute Body Weight [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in absolute body weight
• Change from Randomization in Body Mass Index (BMI) [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in BMI
• Change from Randomization in HbA1c [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in HbA1c
• Percentage of Participants who Achieve HbA1c <7% [ Time Frame: 72 Weeks ]
  Percentage of Participants who Achieve HbA1c <7%
• Percentage of Participants Who Achieve HbA1c ≤6.5% [ Time Frame: 72 Weeks ]
  Percentage of participants who achieve HbA1c ≤6.5%
• Percentage of Participants Who Achieve HbA1c <5.7% [ Time Frame: 72 Weeks ]
  Percentage of participants who achieve HbA1c <5.7%
• Change from Randomization in Fasting Glucose [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in fasting glucose
• Change from Randomization in Waist Circumference [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in waist circumference
• Change from Randomization in Total Cholesterol [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in total cholesterol
• Change from Randomization in Low Density Lipid (LDL)-Cholesterol [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in LDL-cholesterol
• Change from Randomization in High Density Lipid (HDL) Cholesterol [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in HDL cholesterol
• Change from Randomization in Very Low Density Lipid (VLDL) Cholesterol [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in VLDL cholesterol
• Change from Randomization in Triglycerides [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in triglycerides
• Change from Randomization in Free Fatty Acids [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in free fatty acids
• Change from Randomization in Systolic Blood Pressure (SBP) [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in SBP
• Change from Randomization in Diastolic Blood Pressure (DBP) [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in DBP
• Change from Randomization in Fasting Insulin [ Time Frame: Randomization, 72 Weeks ]
  Change from randomization in fasting insulin
• Change from Randomization in Short Form 36 Health Survey version 2 (SF-36v2) acute form Physical Functioning domain score [ Time Frame: Randomization, 72 Weeks ]
  The Short Form 36 Version 2 (SF-36v2 ) acute form, 1-week recall, assesses participants' health-related quality of life (HRQoL) on 8 domains: 1) limitations in physical functioning; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning; 7) limitations in usual role due to emotional problems; and 8) general mental health. Domain scores are norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10, with higher scores indicating better levels of function and/or better health.
• Change from Randomization in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL Lite-CT) Physical Function Composite Score [ Time Frame: Randomization, 72 Weeks ]
  The IWQOL Lite-CT consists of 20 items, assessing 2 primary domains of obesity related 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. Individual composite scale scores and a total score can be computed and are presented on a scale of 0 to 100, with higher scores indicating better function.
• Pharmacokinetics (PK): Steady State Area Under the Concentration Curve (AUC) of Tirzepatide [ Time Frame: Baseline through Week 72 ]
  PK: Steady State AUC of Tirzepatide

• 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 Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight
• Official Title: Efficacy and Safety of Tirzepatide Once Weekly in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-2)
• Brief Summary: This is a study of tirzepatide in participants with type 2 diabetes who have obesity or are overweight. The main purpose is to learn more about how tirzepatide affects body weight. The study will last 79 weeks (22 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
• Overweight
• Obesity

Intervention

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

Study Arms

• Experimental: 10 mg Tirzepatide
  10 mg Tirzepatide administered subcutaneously (SC)
  Intervention: Drug: Tirzepatide
• Experimental: 15 mg Tirzepatide
  15 mg Tirzepatide administered SC
  Intervention: Drug: Tirzepatide
• Placebo Comparator: Placebo
  Placebo administered SC
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: December 1, 2020): 900
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 17, 2023
• Estimated Primary Completion Date: March 20, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have Type 2 Diabetes (T2DM) with HbA1c ≥7% to ≤10% at screening, on stable therapy for the last 3 months prior to screening. T2DM may be treated with diet/exercise alone or any oral glycemic-lowering agent (as per local labeling) EXCEPT dipeptidyl peptidase 4 (DPP-4) inhibitors or glucagon like peptide-1 receptor agonists (GLP-1 RAs)
• Have a BMI of ≥27 kg/m²
• Are overweight or have obesity
• Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight
• Are at least 18 years of age and age of majority per local laws and regulations

Exclusion Criteria:

• Have Type 1 diabetes mellitus, history of ketoacidosis or hyperosmolar state/coma or any other types of diabetes except T2DM
• Have at least 2 confirmed fasting self-monitoring blood glucose (SMBG) values >270 mg/dL(on 2 nonconsecutive days) prior to Visit 3
• Have proliferative diabetic retinopathy OR diabetic macular edema OR non-proliferative diabetic retinopathy that requires acute treatment
• Have self-reported change in body weight >5kg within 3 months prior to screening
• Have had a history of chronic or acute pancreatitis
• 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
• 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, India, Japan, Puerto Rico, Russian Federation, Taiwan, United States
• Removed Location Countries: Mexico

Administrative Information

• NCT Number: NCT04657003
• Other Study ID Numbers: 17245; I8F-MC-GPHL ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No

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

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: https://www.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 2022