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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Phase 2 Study of Once-Weekly LY3298176 Compared With Placebo and Dulaglutide in Patients With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03131687
• Other study ID #: 16335
• Secondary ID: I8F-MC-GPGB2016-
• Status: Completed
• Phase: Phase 2
• Start date: May 24, 2017
• Est. completion date: August 1, 2018

Study information

• Verified date: April 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 318
• Est. completion date: August 1, 2018
• Est. primary completion date: August 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

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

Locations

Country	Name	City	State
Poland	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Gdansk
Poland	"For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician."	Gdynia
Poland	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Gdynia
Poland	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Katowice
Poland	Clinica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária LTDA	Lódz
Poland	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Szczecin
Puerto Rico	Manati Center for Clinical Research	Manati
Puerto Rico	Clinical Research Puerto Rico. Inc	San Juan
Puerto Rico	GCM Medical Group PSC	San Juan
Slovakia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Košice
Slovakia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Malacky
Slovakia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Púchov
Slovakia	"For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."	Trencín
Slovakia	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Trencín
United States	Anaheim Clinical Trails	Anaheim	California
United States	Aventiv Research	Columbus	Ohio
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	The Corvallis Clinic P.C.	Corvallis	Oregon
United States	Dallas Diabetes Endocrine Center	Dallas	Texas
United States	Lillestol Research LLC	Fargo	North Dakota
United States	Valley Research	Fresno	California
United States	National Research Institute	Huntington Park	California
United States	East Coast Institute For Research	Jacksonville	Florida
United States	New Phase Research & Development	Knoxville	Tennessee
United States	PMG Research Of Knoxville	Knoxville	Tennessee
United States	Palm Research Center	Las Vegas	Nevada
United States	National Research Institute	Los Angeles	California
United States	Solaris Clinical Research	Meridian	Idaho
United States	ActivMed Practices & Research	Methuen	Massachusetts
United States	New Horizon Research Center	Miami	Florida
United States	Suncoast Research Group, LCC	Miami	Florida
United States	Internal Medicine Center LLC	Mobile	Alabama
United States	PMG Research Of Charleston LLC	Moncks Corner	South Carolina
United States	Catalina Research Institute	Montclair	California
United States	Manhattan Medical Research	New York	New York
United States	Valley Clinical Trails, Inc	Northridge	California
United States	Sensible Healthcare	Ocoee	Florida
United States	Palm Harbor Medical Associate	Palm Harbor	Florida
United States	Chrysalis Clinical Research	Saint George	Utah
United States	Clinical Research Professionals	Saint Louis	Missouri
United States	Artemis Institute For Clinical Research	San Diego	California
United States	Artemis Institute For Clinical Research	San Marcos	California
United States	Consano Clinical Research	Shavano Park	Texas
United States	Encompass Clinical Research	Spring Valley	California
United States	Cotton O'Neil Diabetes and Endocrine	Topeka	Kansas
United States	Premier Research	Trenton	New Jersey
United States	University Clinical Investigators INC	Tustin	California
United States	Chase Medical Research	Waterbury	Connecticut
United States	Iderc P.L.C.	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Poland,  Puerto Rico,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) Bayesian Dose Response	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.	Baseline, Week 26
Secondary	Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) Bayesian Dose Response	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.	Baseline, Week 12
Secondary	Change From Baseline to Week 26 in HbA1c	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.	Baseline, Week 26
Secondary	Change From Baseline to Week 12 in HbA1c	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.	Baseline, Week 12
Secondary	Change From Baseline in Body Weight	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.	Baseline, Week 26
Secondary	Percentage of Participants With 5% or Greater Body Weight Loss From Baseline	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.	Week 26
Secondary	Percentage of Participants With 10% or Greater Body Weight Loss From Baseline	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.	Week 26
Secondary	Percentage of Participants Reaching the HbA1c Target of =6.5%	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.	Week 26
Secondary	Percentage of Participants Reaching the HbA1c Target of <7.0%	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.	Week 26
Secondary	Change From Baseline in Fasting Blood Glucose	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.	Baseline, Week 26
Secondary	Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)	LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag,Treatment, time, treatment*time.	Baseline, Week 26
Secondary	Change From Baseline in Total Cholesterol	LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.	Baseline, Week 26
Secondary	Change From Baseline in Triglycerides	LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.	Baseline, Week 26
Secondary	Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)	LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.	Baseline, Week 26
Secondary	Change From Baseline in Waist Circumference	LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.	Baseline, Week 26
Secondary	Number of Participants With Anti-Drug Antibodies	Number of Participants With Anti-Drug Antibodies.	Baseline through Week 30
Secondary	Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide	Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide	Predose: Week 1,8,12 and 26; Postdose: Week 1,2,4 and 12

External Links

•   A Study of tirzepatide in Participants With Type 2 Diabetes Mellitus