A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Mellitus

Overview

The purpose of this study is to evaluate the efficacy of the study drug tirzepatide in participants with type 2 diabetes mellitus.

Full Title of Study: “A Phase 2 Study of Once-Weekly LY3298176 Compared With Placebo and Dulaglutide in Patients With Type 2 Diabetes Mellitus”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: August 1, 2018

Interventions

  • Drug: tirzepatide
    • Administered SC
  • Drug: Dulaglutide
    • Administered SC
  • Drug: Placebo
    • Administered SC

Arms, Groups and Cohorts

  • Placebo Comparator: Placebo
    • Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.
  • Experimental: 1 mg Tirzepatide
    • 1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
  • Experimental: 5 mg Tirzepatide
    • 5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
  • Experimental: 10 mg Tirzepatide
    • 10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
  • Experimental: 15 mg Tirzepatide
    • 15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
  • Active Comparator: 1.5 mg Dulaglutide
    • 1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.

Clinical Trial Outcome Measures

Primary Measures

  • Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) Bayesian Dose Response
    • Time Frame: Baseline, Week 26
    • HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.This was a Bayesian dose response analysis of HbA1c (%) change from baseline. At baseline: Mean (SD = Standard Deviation) of baseline HbA1c (%). After baseline: Posterior Mean (SD = Posterior Standard Deviation) of HbA1c (%) change from baseline. The Least Squares Mean is Posterior mean.

Secondary Measures

  • Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) Bayesian Dose Response
    • Time Frame: Baseline, Week 12
    • HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. This was a Bayesian dose response analysis of HbA1c (%) change from baseline. At baseline: Mean (SD = Standard Deviation) of baseline HbA1c (%). After baseline: Posterior Mean (SD = Posterior Standard Deviation) of HbA1c (%) change from baseline. The Least Squares Mean is Posterior mean.
  • Change From Baseline to Week 26 in HbA1c
    • Time Frame: Baseline, Week 26
    • HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: Baseline + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.
  • Change From Baseline to Week 12 in HbA1c
    • Time Frame: Baseline, Week 12
    • HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: Baseline + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.
  • Change From Baseline in Body Weight
    • Time Frame: Baseline, Week 26
    • Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with independent variables: Baseline + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.
  • Percentage of Participants With 5% or Greater Body Weight Loss From Baseline
    • Time Frame: Week 26
    • Percentage of participants with 5% or greater body weight loss from baseline last observation carried forward (LOCF) analyses using Logistic regression model with Baseline value + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin + Treatment as factors.
  • Percentage of Participants With 10% or Greater Body Weight Loss From Baseline
    • Time Frame: Week 26
    • Percentage of participants with 10% or greater body weight loss from baseline LOCF analyses using Logistic regression model with Baseline value + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin + Treatment as factors.
  • Percentage of Participants Reaching the HbA1c Target of ≤6.5%
    • Time Frame: Week 26
    • Percentage of participants with HbA1c ≤6.5% at Week 26 using a logistic regression model for endpoint used last observation carried forward (LOCF) method including baseline value, baseline BMI Group, baseline Metformin and treatment as factors.
  • Percentage of Participants Reaching the HbA1c Target of <7.0%
    • Time Frame: Week 26
    • Percentage of participants with HbA1c <7.0% at Week 26 using a logistic regression model for endpoint used last observation carried forward (LOCF) method including baseline value, baseline BMI Group, baseline Metformin and treatment as factors.
  • Change From Baseline in Fasting Blood Glucose
    • Time Frame: Baseline, Week 26
    • Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates: Baseline + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.
  • Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
    • Time Frame: Baseline, Week 26
    • LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag,Treatment, time, treatment*time.
  • Change From Baseline in Total Cholesterol
    • Time Frame: Baseline, Week 26
    • LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.
  • Change From Baseline in Triglycerides
    • Time Frame: Baseline, Week 26
    • LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.
  • Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)
    • Time Frame: Baseline, Week 26
    • LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.
  • Change From Baseline in Waist Circumference
    • Time Frame: Baseline, Week 26
    • LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.
  • Number of Participants With Anti-Drug Antibodies
    • Time Frame: Baseline through Week 30
    • Number of Participants With Anti-Drug Antibodies.
  • Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide
    • Time Frame: Predose: Week 1,8,12 and 26; Postdose: Week 1,2,4 and 12
    • Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide

Participating in This Clinical Trial

Inclusion Criteria

  • Have had type 2 diabetes (T2D) for ≥6 months according to the World Health Organization (WHO) classification. – Have HbA1c of 7.0% to 10.5%, inclusive, as assessed by the central laboratory. – If on metformin, have been treated with stable doses of metformin for at least 3 months. – Have a body mass index (BMI) ≥23 and <50 kilograms per square meter. Exclusion Criteria:

  • Have type 1 diabetes (T1D). – Have used any glucose-lowering medication other than metformin within 3 months prior to study entry or during screening/lead-in period or have used any glucagon-like peptide-1 receptor agonists (GLP-1 RAs) at any time in the past. – Have had any of the following cardiovascular conditions: acute myocardial infarction (MI), New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident (stroke). – Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level >2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial. – Have had chronic or acute pancreatitis any time prior to study entry. – Have an estimated glomerular filtration rate (eGFR) <45 milliliters/minute/1.73 square meter, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation. – Have serum calcitonin ≥20 picograms per milliliter, as determined by the central laboratory at study entry. – Have any condition that is a contraindication for use of the GLP-1 RA class (per country-specific labels) at study entry or develop such condition between study entry and randomization.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Eli Lilly and Company
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • 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), Study Director, Eli Lilly and Company

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