A Study of Tirzepatide (LY3298176) in Participants With Obesity Disease (SURMOUNT-J)

Efficacy and Safety of Once-Weekly Tirzepatide in Participants With Obesity Disease: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-J)

The main purpose of this study is to learn more about tirzepatide in participants with obesity disease. The study will also measure how Tirzepatide affects body weight with a low-calorie diet and increased physical activity. The study will last around 72 Weeks.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Tirzepatide; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 267
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 530-0001
    • AMC Nishiumeda Clinic
  • Chiba
    • Ichikawa, Chiba, Japan, 272-8516
      • Kohnodai Hospital, National Center for Global Health and Medicine
  • Ehime
    • Matsuyama, Ehime, Japan, 791-8026
      • Saiseikai Matsuyama Hospital
  • Kanagawa
    • Kamakura-shi, Kanagawa, Japan, 247-0056
      • Takai Internal Medicine Clinic
    • Yokohama, Kanagawa, Japan, 2308765
      • Saiseikai Yokohamashi Tobu Hospital
    • Yokohama-city, Kanagawa, Japan, 231-0023
      • Motomachi Takatsuka Naika Clinic
  • Osaka
    • Suita, Osaka, Japan, 564-0013
      • Osaka Saiseikai Suita hospital
    • Suita-shi, Osaka, Japan, 565-0853
      • Medical Corporation Heishinkai OCROM Clinic
    • Takatsuki, Osaka, Japan, 569-1045
      • Takatsuki Red Cross Hospital
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 103-0027
      • Tokyo-Eki Center-building Clinic
    • Chuo-ku, Tokyo, Japan, 104-0031
      • Fukuwa Clinic
    • Chuo-ku, Tokyo, Japan, 103-0028
      • Medical Corporation Chiseikai Tokyo Center Clinic
    • Chuo-ku, Tokyo, Japan, 103-0002
      • The Institute for Adult Disease, Asahi Life Foundation
    • Minato-Ku, Tokyo, Japan, 108-0073
      • Saiseikai Central Hospital
    • Setagaya-ku, Tokyo, Japan, 155-0031
      • Shimokitazawa Tomo Clinic
    • Shinagawa-ku, Tokyo, Japan, 141 0032
      • Miho Clinic
    • Shinjuku-ku, Tokyo, Japan, 160 0008
      • Medical Corporation Heishinkai ToCROM Clinic
  • Yamagata
    • Yamagata-shi, Yamagata, Japan, 990-0834
      • Yamagata Tokushukai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a BMI of greater than or equal to ≥27 kg/m² and <less than 35 kg/m² with at least 2 obesity-related health problems or ≥35 kg/m² with at least 1 obesity-related health problems. Health problems are IGT, hyperlipidemia, or NAFLD.
• Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight.

Exclusion Criteria:

• Have diabetes.
• Acute or chronic liver disease other than NAFLD.
• Have a self-reported change in body weight >5 kg within 3 months 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.
• Have renal impairment measured as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, calculated by Japanese Society of Nephrology coefficient-modified Chronic Kidney Disease-Epidemiology equation during screening.
• Have a known clinically significant gastric emptying abnormality.
• Have had a history of chronic or acute pancreatitis.
• Have thyroid-stimulating hormone outside of the range of 0.4 to 6.0 micro units per milliliter (μIU/mL) at screening.
• Have obesity induced by other endocrinologic disorders or diagnosed monogenetic or syndromic forms of obesity.
• Have a history of significant active or unstable major depressive disorder or other severe psychiatric disorder within the last 2 years.
• Have a cardiovascular condition within 3 months prior to randomization
• Have a family or personal history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia Syndrome type 2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 15 mg Tirzepatide; Participants received maintenance dose 15 mg with dose escalation starting from 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg and then 15 mg tirzepatide administered SC QW.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: 10 Milligrams (mg) Tirzepatide; Participants received maintenance dose 10 mg with dose escalation starting from 2.5 mg, 5 mg, 7.5 mg and then 10 mg tirzepatide administered subcutaneously (SC) once weekly (QW).	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Placebo Comparator: Placebo; Participants received matching placebo administered SC QW.	Other: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Body Weight	Mean percent change in body weight was measured. Least squares (LS) mean was determined using mixed model repeated measures (MMRM) model with Baseline + impaired glucose tolerance (IGT) at Screening + Hyperlipidemia at Screening + non-alcoholic fatty liver disease (NAFLD) at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, 72 Weeks
Percentage of Participants Who Achieve ≥5% Body Weight Reduction	Percentage of Participants Who Achieve ≥5% Body Weight Reduction	Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Had Improvement in Obesity-related Health Problems	Percentage of participants who had improvement in obesity-related health problems	Week 72
Change From Baseline in Fasting Glucose for Participants With IGT at Baseline	Change from Baseline in Fasting Glucose for Participants with IGT at Baseline. LS mean was determined by MMRM model with = Baseline + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Change From Baseline in Oral Glucose Tolerance (OGTT) 2-hr Glucose for Participants With Impaired Glucose Tolerance (IGT) at Baseline	Change from Baseline in OGTT 2-hr Glucose for Participants with IGT at Baseline. LS mean was determined by MMRM model with Baseline + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Percent Change From Baseline in Fasting Lipids [Triglycerides (TG)] for Participants With Hyperlipidemia at Baseline	Percent Change from Baseline in Fasting Lipids TG for Participants with Hyperlipidemia at Baseline. LS mean was determined by MMRM model with log (Baseline) + NAFLD at Screening + IGT at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Percent Change From Baseline in Hepatic Fat Fraction (HFF) for Participants With Non-alcoholic Fatty Liver Disease [NAFLD]	Percent Change from Baseline in HFF for participants diagnosed as NAFLD by MRI at Baseline. LS mean was determined by ANCOVA model with Baseline + Hyperlipidemia at Screening + IGT at Screening + Sex + Treatment (Type III sum of squares) as variables. Percent Change from Baseline in HFF for participants with NAFLD is reported. NAFLD was diagnosed by Magnetic Resonance Imaging (MRI) at Baseline. This was evaluated only for participants who were diagnosed with NAFLD at baseline by MRI.	Baseline, Week 72
Percentage of Participants Who Achieved Improvements of IGT	Percentage of Participants Who Achieved Improvements of IGT. This was evaluated only for participants with IGT at baseline.	Week 72
Percentage of Participants Who Achieved Improvements of Hyperlipidemia	Percentage of Participants Who Achieved Improvements of Hyperlipidemia. This was evaluated only for participants with hyperlipidemia at baseline.	Week 72
Percentage of Participants Who Achieved Improvements of NAFLD	Percentage of Participants Who Achieved Improvements of NAFLD. This was evaluated only for participants who were diagnosed as NAFLD by MRI at Baseline.	Week 72
Percentage of Participants Who Achieve ≥10% Body Weight Reduction	Percentage of Participants Who Achieve ≥10% body weight reduction.	Week 72
Percentage of Participants Who Achieve ≥15% Body Weight Reduction	Percentage of Participants Who Achieve ≥15% body weight reduction.	Week 72
Change From Baseline in Absolute Body Weight	Change from Baseline in Absolute Body Weight. LS mean was determined by MMRM model with Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Change From Baseline in Body Mass Index (BMI)	Change from Baseline in BMI. LS mean was determined using MMRM model with Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Percent Change From Baseline in Visceral Adipose Tissue (VAT)	Percent Change from Baseline in VAT. LS mean was determined by MMRM model with Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Percent Change From Baseline in Subcutaneous Adipose Tissue (SAT)	Percent Change from Baseline in SAT. LS mean was determined by MMRM model with Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Change From Baseline in VAT/SAT Ratio	Change from Baseline in VAT/SAT Ratio. LS mean was determined by MMRM model with Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Percentage of Participants Who Achieved VAT <100 Square Centimeter (cm²) From Baseline for Participants With VAT≥100 cm² at Baseline	Percentage of Participants Who Achieve VAT <100 cm² from Baseline for participants with VAT≥100 cm² at Baseline.	Week 72
Change From Baseline in Waist Circumference	Change from Baseline in Waist Circumference. LS mean was determined using MMRM model with = Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Change From Baseline in Hemoglobin A1c (HbA1c)	Change from Baseline in HbA1c was assessed only for Participants with IGT at Baseline. LS mean was determined using MMRM model with = Baseline + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Change From Baseline in Fasting Insulin for Participants With IGT at Baseline	Change from Baseline in Fasting Insulin for Participants with IGT at Baseline. LS mean was determined using MMRM model log(Baseline) + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Change From Baseline in Systolic Blood Pressure	Change from Baseline in Systolic Blood Pressure. LS mean was determined using MMRM model with Baseline + Hyperlipidemia at Screening + NAFLD at Screening + IGT at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Change From Baseline in Diastolic Blood Pressure	Change from Baseline in Diastolic Blood Pressure. LS mean was determined using MMRM model with Baseline + Hyperlipidemia at Screening + NAFLD at Screening + IGT at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72
Change From Baseline in Short Form 36 Version 2 Health Survey (SF-36v2) Acute Form Physical Functioning Domain Score	The SF-36v2 acute form, 1-week recall assesses participants' health-related quality of life (HRQoL) on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Information from these 8 domains is further aggregated into 2 health component summary scores: Physical Component Summary and Mental Component Summary. Items are answered on Likert scales of varying lengths. Scoring of each domain and both summary scores are norm based and presented in the form of T scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function and/or better health. Range cannot be specified in norm-based scores. LS mean was determined using ANCOVA model with Week 0 (Visit 3) + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment (Type III sum of squares) as variables.	Baseline, Week 72
Change From Baseline in Impact of Weight on Quality-of-Life Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score	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. 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. LS mean was determined using ANCOVA model with Week 0 (Visit 3) + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment (Type III sum of squares) as variables.	Baseline, Week 72
Change From Baseline in Euro Quality of Life Five Dimensions (EQ-5D-5L)	The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It comprises of 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, unable to perform/extreme problems). In addition to the health profile, a single health state index value can be derived based on a formula that attaches weights to each of the levels in each dimension. This index value ranges between ˂0 (where 0 is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). LS mean was determined using ANCOVA model with Week 0 (Visit 3) + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment (Type III sum of squares) as variables.	Baseline, Week 72

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• 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

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Actual): June 24, 2023
• Study Completion (Actual): June 24, 2023

Study Registration Dates

• First Submitted: April 1, 2021
• First Submitted That Met QC Criteria: April 12, 2021
• First Posted (Actual): April 14, 2021

Study Record Updates

• Last Update Posted (Actual): July 16, 2024
• Last Update Submitted That Met QC Criteria: June 20, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Metabolism and Nutrition Disorder; Obesity Related Health Problems; Obesity Disease
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: 17506; I8F-JE-GPHZ (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes