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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03131687
Recruitment Status : Completed
First Posted : April 27, 2017
Results First Posted : August 20, 2019
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: tirzepatide Drug: Dulaglutide Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 318 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Once-Weekly LY3298176 Compared With Placebo and Dulaglutide in Patients With Type 2 Diabetes Mellitus
Actual Study Start Date : May 24, 2017
Actual Primary Completion Date : August 1, 2018
Actual Study Completion Date : August 1, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Dulaglutide

Arm Intervention/treatment
Placebo Comparator: Placebo
Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.
Drug: Placebo
Administered SC

Experimental: 1 mg Tirzepatide
1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Drug: tirzepatide
Administered SC
Other Name: LY3298176

Drug: Placebo
Administered SC

Experimental: 5 mg Tirzepatide
5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Drug: tirzepatide
Administered SC
Other Name: LY3298176

Drug: Placebo
Administered SC

Experimental: 10 mg Tirzepatide
10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Drug: tirzepatide
Administered SC
Other Name: LY3298176

Drug: Placebo
Administered SC

Experimental: 15 mg Tirzepatide
15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Drug: tirzepatide
Administered SC
Other Name: LY3298176

Drug: Placebo
Administered SC

Active Comparator: 1.5 mg Dulaglutide
1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Drug: Dulaglutide
Administered SC
Other Name: LY2189265

Drug: Placebo
Administered SC




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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.


  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Number of Participants With Anti-Drug Antibodies [ Time Frame: Baseline through Week 30 ]
    Number of Participants With Anti-Drug Antibodies.

  16. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03131687


  Show 49 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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 Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] November 28, 2017
Statistical Analysis Plan  [PDF] March 26, 2018


Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03131687     History of Changes
Other Study ID Numbers: 16335
I8F-MC-GPGB ( Other Identifier: Eli Lilly and Company )
2016-004179-33 ( EudraCT Number )
First Posted: April 27, 2017    Key Record Dates
Results First Posted: August 20, 2019
Last Update Posted: August 20, 2019
Last Verified: April 2019
Individual Participant Data (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
Statistical Analysis Plan (SAP)
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: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Dulaglutide
Immunoglobulin Fc Fragments
Hypoglycemic Agents
Physiological Effects of Drugs
Immunologic Factors