A Study of Investigational Dulaglutide Doses in Participants With Type 2 Diabetes on Metformin Monotherapy

A Phase 2, Double-Blind, Placebo-Controlled, 18-Week Trial of Investigational Dulaglutide Doses Versus Placebo in Patients With Type 2 Diabetes on Metformin Monotherapy

The purpose of this study is to evaluate the efficacy and safety of investigational doses of dulaglutide in participants with type 2 diabetes on metformin monotherapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Dulaglutide

• Study Type: Interventional
• Enrollment (Actual): 318
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brandýs Nad Labem-Stará Boleslav, Czechia, 25001
    • 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.
  • Krnov, Czechia, 79401
    • 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.
  • Praha 1, Czechia, 11000
    • 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.
  • Praha 4, Czechia, 149 00
    • 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.
  • Praha 4 - Krc, Czechia, 140 59
    • 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.
  • Praha 8, Czechia, 181 00
    • 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.
• Mexico
  • Chihuahua, Mexico, 31217
    • 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.
  • Cuernavaca, Mexico, 62250
    • 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.
  • Guadalajara, Mexico, 04460
    • 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.
  • Monterrey, Mexico, 64460
    • 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.
  • Tampico, Mexico, 89000
    • 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.
• Poland
  • Bialystok, Poland, 15-404
    • 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.
  • Bialystok, Poland, 15-445
    • 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.
  • Gdansk, Poland, 80-546
    • 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.
  • Lodz, Poland, 90-242
    • 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.
  • Lublin, Poland, 20-538
    • 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.
  • Lublin, Poland, 20-333
    • 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.
  • Poznan, Poland, 61-655
    • 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.
  • Poznan, Poland, 61-853
    • 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.
  • Ruda Slaska, Poland, 41-709
    • 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.
  • Szczecin, Poland, 70-506
    • 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.
• Puerto Rico
  • Manati, Puerto Rico, 00674
    • Marginal Doctor's Center
  • San Juan, Puerto Rico, 00917
    • American Telemedicine Center
• Romania
  • Alba Iulia, Romania, 510053
    • 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.
  • Baia Mare, Romania, 430222
    • 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.
  • Iasi, Romania, 700547
    • 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.
  • Oradea, Romania, 410159
    • 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.
  • Satu-Mare, Romania, 440055
    • 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.
• United States
  • California
    • Glendale, California, United States, 91206-4140
      • Parexel Early Phase Unit at Glendale
    • Greenbrae, California, United States, 94904
      • Marin Endocrine Associates
    • Huntington Park, California, United States, 90255
      • National Research Institute
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • Spring Valley Lake, California, United States, 91978
      • Encompass Clinical Research
    • Tustin, California, United States, 92780
      • University Clinical Investigators, Inc.
    • Van Nuys, California, United States, 91405
      • Infosphere
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Florida
    • Cooper City, Florida, United States, 33024
      • Axes Medical Research, LLC
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Jacksonville, Florida, United States, 32204
      • East Coast Institute for Research
    • Miami, Florida, United States, 33175
      • New Horizon Research Center
    • Miami Lakes, Florida, United States, 33135
      • Suncoast Research Group, LLC
    • Palm Harbor, Florida, United States, 34684
      • Palm Harbor Medical Associates
  • Georgia
    • Norcross, Georgia, United States, 30071
      • In-Quest Medical Research, LLC - Norcross
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Medical Institute
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Elite Cilnical Trials LLLP
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
  • Illinois
    • Springfield, Illinois, United States, 62711
      • HSHS Medical Group Diabetes Research
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • American Health Network
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Iderc, P.L.C.
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Diabetes and Endocrinology Center
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, Inc
  • Missouri
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research, LLC
  • New York
    • New York Mills, New York, United States, 10016
      • Manhattan Medical Research
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • High Point Clinical Trials Center
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • The Corvallis Clinic P.C.
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Heritage Valley Medical Group, Inc.
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • New Phase Research & Development
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Endocrine Center
    • San Antonio, Texas, United States, 78231
      • Consano Clinical Research
    • Waxahachie, Texas, United States, 75165
      • Clinpoint Trial, LLC
  • Utah
    • Saint George, Utah, United States, 84790
      • Chrysalis Clinical Research
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 10.0%, inclusive, as assessed by the central laboratory
• Have been treated with stable doses of metformin for at least 3 months
• Have a body mass index (BMI) ≥25 kilograms per square meter

Exclusion Criteria:

• Have type 1 diabetes (T1D)
• Have used any glucose-lowering medication other than metformin 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo administered SC	Drug: Placebo; Administered SC
Experimental: Dulaglutide 4.5mg; 4.5mg of Dulaglutide administered subcutaneously (SC)	Drug: Dulaglutide; Administered SC; Other Names: LY2189265
Experimental: Dulaglutide 3.0mg; 3.0mg of Dulaglutide administered SC	Drug: Dulaglutide; Administered SC; Other Names: LY2189265
Active Comparator: Dulaglutide 1.5mg; 1.5mg of Dulaglutide administered SC	Drug: Dulaglutide; Administered SC; Other Names: LY2189265

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c)	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline as a covariate, pooled country, treatment, time, treatment*time as fixed effects.	Baseline, Week 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HbA1c of <7.0%	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Week 18
Change From Baseline in Fasting Serum Glucose (FSG)	Fasting serum glucose (FSG) is a test to determine how much glucose (sugar) is in a serum sample after an overnight fast. Least Squares (LS) means was determined by MMRM methodology with baseline as a covariate, pooled country, baseline HbA1c strata using >=8% as cutoff, treatment, time, treatment*time as fixed effects.	Baseline, Week 18
Change From Baseline in Body Weight	Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline as a covariate, pooled country, baseline HbA1c strata using >=8% as cutoff, treatment, time, treatment*time as fixed effects.	Baseline, Week 18
Percentage of Participants Discontinuing Study Drug Due to Adverse Events	Adverse event (AE) defined as any unfavorable medical event, newly emerged or a deterioration of a preexisting condition, in other words any untoward medical occurrence in a patient administered a pharmaceutical product, without regard to the possibility of a causal relationship, that occurred after the visit for informed consent and up to the visit for completion of administration, or discontinuation.	Baseline through Week 18
Rate of Documented Symptomatic Hypoglycemia	Hypoglycemic events (HE) were classified as severe, documented symptomatic (defined as an HE with typical symptoms of hypoglycemia and a blood glucose level of ≤3.9 millimoles per liter [mmol/L]). Hypoglycemia rate per 30 days was summarized at each visit by treatment group. The rate of hypoglycemia was analyzed using a generalized estimation equations model with a negative binomial distribution and a Log link. LS mean was determined by MMRM methodology with baseline hypoglycemia rate, pooled country, HbA1c at Baseline, treatment, with log of exposure in days divided by 365.25 as the offset.	Week 18
Pharmacokinetics (PK): The Maximum Drug Concentration at Steady State (Cmax,ss) of Dulaglutide	Plasma samples for PK analysis were combined measure obtained from 0, 2, 4, 6, 10, 18, 22 weeks and until early termination of the visit. Cmax takes all time points post dose into account and one value was reported.	0, 2, 4, 6, 10, 18, 22 weeks and early termination
Pharmacokinetics: Area Under the Concentration-Time Curve at Steady State From Time Zero to 168 Hours (AUC[0-168], ss) of Dulaglutide	AUC[0-168h] is a combined measure obtained from 0, 2, 4, 6, 10, 18, 22 weeks and until early termination of the visit.	0, 2, 4, 6, 10, 18, 22 weeks and early termination

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of Investigational Dulaglutide Doses in Participants With Type 2 Diabetes on Metformin Monotherapy

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): July 15, 2017
• Study Completion (Actual): August 14, 2017

Study Registration Dates

• First Submitted: November 22, 2016
• First Submitted That Met QC Criteria: November 22, 2016
• First Posted (Estimate): November 25, 2016

Study Record Updates

• Last Update Posted (Actual): September 23, 2019
• Last Update Submitted That Met QC Criteria: September 5, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Dulaglutide
• Other Study ID Numbers: 16568; H9X-MC-GBGJ (Other Identifier: Eli Lilly and Company); 2016-002494-34 (EudraCT Number)

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 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