A Study of Tirzepatide (LY3298176) in Participants With Obesity Disease
- Registration Number
- NCT04844918
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 267
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received matching placebo administered SC QW. 10 Milligrams (mg) Tirzepatide 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). 15 mg Tirzepatide 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.
- Primary Outcome Measures
Name Time Method Mean Percent Change in Body Weight Baseline, 72 Weeks 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.
Percentage of Participants Who Achieve ≥5% Body Weight Reduction Week 72 Percentage of Participants Who Achieve ≥5% Body Weight Reduction
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Hepatic Fat Fraction (HFF) for Participants With Non-alcoholic Fatty Liver Disease [NAFLD] Baseline, Week 72 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.
Percentage of Participants Who Achieve ≥10% Body Weight Reduction Week 72 Percentage of Participants Who Achieve ≥10% body weight reduction.
Percentage of Participants Who Achieve ≥15% Body Weight Reduction Week 72 Percentage of Participants Who Achieve ≥15% body weight reduction.
Change From Baseline in Hemoglobin A1c (HbA1c) Baseline, Week 72 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.
Change From Baseline in Fasting Insulin for Participants With IGT at Baseline Baseline, Week 72 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.
Change From Baseline in Fasting Glucose for Participants With IGT at Baseline Baseline, Week 72 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.
Percent Change From Baseline in Fasting Lipids [Triglycerides (TG)] for Participants With Hyperlipidemia at Baseline Baseline, Week 72 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.
Percentage of Participants Who Had Improvement in Obesity-related Health Problems Week 72 Percentage of participants who had improvement in obesity-related health problems
Percentage of Participants Who Achieved Improvements of IGT Week 72 Percentage of Participants Who Achieved Improvements of IGT. This was evaluated only for participants with IGT at baseline.
Change From Baseline in VAT/SAT Ratio Baseline, Week 72 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.
Change From Baseline in Systolic Blood Pressure Baseline, Week 72 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.
Change From Baseline in Oral Glucose Tolerance (OGTT) 2-hr Glucose for Participants With Impaired Glucose Tolerance (IGT) at Baseline Baseline, Week 72 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.
Percentage of Participants Who Achieved Improvements of Hyperlipidemia Week 72 Percentage of Participants Who Achieved Improvements of Hyperlipidemia. This was evaluated only for participants with hyperlipidemia at baseline.
Percentage of Participants Who Achieved Improvements of NAFLD Week 72 Percentage of Participants Who Achieved Improvements of NAFLD. This was evaluated only for participants who were diagnosed as NAFLD by MRI at Baseline.
Percent Change From Baseline in Subcutaneous Adipose Tissue (SAT) Baseline, Week 72 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.
Change From Baseline in Diastolic Blood Pressure Baseline, Week 72 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.
Change From Baseline in Euro Quality of Life Five Dimensions (EQ-5D-5L) Baseline, Week 72 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.Change From Baseline in Absolute Body Weight Baseline, Week 72 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.
Change From Baseline in Body Mass Index (BMI) Baseline, Week 72 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.
Percent Change From Baseline in Visceral Adipose Tissue (VAT) Baseline, Week 72 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.
Percentage of Participants Who Achieved VAT <100 Square Centimeter (cm²) From Baseline for Participants With VAT≥100 cm² at Baseline Week 72 Percentage of Participants Who Achieve VAT \<100 cm² from Baseline for participants with VAT≥100 cm² at Baseline.
Change From Baseline in Waist Circumference Baseline, Week 72 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.
Change From Baseline in Short Form 36 Version 2 Health Survey (SF-36v2) Acute Form Physical Functioning Domain Score Baseline, Week 72 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.Change From Baseline in Impact of Weight on Quality-of-Life Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score Baseline, Week 72 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.
Trial Locations
- Locations (18)
Takatsuki Red Cross Hospital
🇯🇵Takatsuki, Osaka, Japan
Saiseikai Matsuyama Hospital
🇯🇵Matsuyama, Ehime, Japan
Motomachi Takatsuka Naika Clinic
🇯🇵Yokohama-city, Kanagawa, Japan
Kohnodai Hospital, National Center for Global Health and Medicine
🇯🇵Ichikawa, Chiba, Japan
Takai Internal Medicine Clinic
🇯🇵Kamakura-shi, Kanagawa, Japan
Medical Corporation Heishinkai OCROM Clinic
🇯🇵Suita-shi, Osaka, Japan
The Institute for Adult Disease, Asahi Life Foundation
🇯🇵Chuo-ku, Tokyo, Japan
Saiseikai Central Hospital
🇯🇵Minato-Ku, Tokyo, Japan
Yamagata Tokushukai Hospital
🇯🇵Yamagata-shi, Yamagata, Japan
Miho Clinic
🇯🇵Shinagawa-ku, Tokyo, Japan
AMC Nishiumeda Clinic
🇯🇵Osaka, Japan
Osaka Saiseikai Suita hospital
🇯🇵Suita, Osaka, Japan
Medical Corporation Chiseikai Tokyo Center Clinic
🇯🇵Chuo-ku, Tokyo, Japan
Medical Corporation Heishinkai ToCROM Clinic
🇯🇵Shinjuku-ku, Tokyo, Japan
Fukuwa Clinic
🇯🇵Chuo-ku, Tokyo, Japan
Saiseikai Yokohamashi Tobu Hospital
🇯🇵Yokohama, Kanagawa, Japan
Shimokitazawa Tomo Clinic
🇯🇵Setagaya-ku, Tokyo, Japan
Tokyo-Eki Center-building Clinic
🇯🇵Chuo-ku, Tokyo, Japan