A Study to Compare a New Drug for Type 2 Diabetes to Placebo and to a Treatment Already Available for Type 2 Diabetes

Comparison of the Oxyntomodulin Analog, LY2944876, to Once-Weekly Exenatide and to Placebo in Patients With Type 2 Diabetes

The main purpose of this study is to compare the safety and effectiveness of the study drug known as LY2944876 to exenatide extended-release and placebo in participants with type 2 diabetes mellitus. All drugs will be given by an injection under the skin. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry. Participants' involvement in the study is expected to last about 30 weeks.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: Metformin; Drug: LY2944876; Drug: Exenatide extended-release

Detailed Description

The study will include a 12 week blinded treatment period, where neither the participant nor the investigator will know to which treatment each individual is assigned. Thereafter follows a 12 week period where participants and the investigator will know which treatment they are assigned to. Participants' on LY2944876 and on exenatide extended-release continue treatment in this period, those who received placebo will be followed without treatment.

• Study Type: Interventional
• Enrollment (Actual): 420
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Ampelokipoi, Greece, 11527
    • 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.
  • Athens, Greece, 11527
    • 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.
  • Thessaloniki, Greece, 57010
    • 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, 31238
    • 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, 44690
    • 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, 15-351
    • 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.
  • Gdynia, Poland, 81-553
    • 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.
  • 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.
  • 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.
  • Warsaw, Poland, 01-518
    • 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
    • Manati Medical Center
  • San Juan, Puerto Rico, 00917-3104
    • American Telemedicine Center
• Romania
  • Cluj-Napoca, Romania, 400349
    • 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.
  • Iaşi, 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.
  • Ploiesti, Romania, 100342
    • 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.
  • Targu Mures, Romania, 540098
    • 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.
  • Timisoara, Romania, 300456
    • 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
    • Concord, California, United States, 94520
      • John Muir Physician Network Clinical Research Center
    • Fresno, California, United States, 93720
      • Valley Endocrine, Fresno
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • Palm Springs, California, United States, 92262
      • Desert Medical Group Inc
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
  • Florida
    • Bradenton, Florida, United States, 34208
      • Meridien Research
    • Fort Lauderdale, Florida, United States, 33316
      • M & O Clinical Research, LLC
    • Miami, Florida, United States, 33135
      • Suncoast Research Group, LLC
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research
    • Oviedo, Florida, United States, 32765
      • Compass Research
    • Winter Haven, Florida, United States, 33880
      • Clinical Research of Central Florida
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Medical Institute
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Diabetes and Osteoporosis Center
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Iderc, P.L.C.
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Diabetes and Endocrinology Center
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • St John's Mercy Medical Center
    • Springfield, Missouri, United States, 65807
      • Mercy Medical Research Institute
    • Washington, Missouri, United States, 63090
      • Mercy Health Research
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Southern New Hampshire Diabetes and Endocrinology
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • High Point Clinical Trials Center
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Lillestol Research LLC
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • The Corvallis Clinic P.C.
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Blair Medical Associates, Inc.
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Diabetes and Endocrinology
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Endocrine Center
    • Georgetown, Texas, United States, 78626
      • San Gabriel Clinical Research
    • San Antonio, Texas, United States, 78218
      • Oakwell Clinical Research
    • Sugar Land, Texas, United States, 77478
      • Southwest Health Associates, P.A.
  • Utah
    • Bountiful, Utah, United States, 84010
      • Wade Family Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women with diabetes mellitus Type 2
• Have screening HbA1c ≥7.0% and ≤10.5% either on diet and exercise alone or on a stable dose of metformin (≥1000 mg/day) for 3 months prior to screening
• Have body mass index (BMI) ≥23 and ≤45 kilograms per meter squared at screening

Exclusion Criteria:

• Women of child bearing potential
• Participants who have used thiazolidinediones within 3 months prior to screening, or any other drugs for treatment of hyperglycemia (except metformin) within the prior 2 months
• Participants who have used insulin for diabetic control for more than 6 consecutive days within the prior year
• Participants with impaired renal function (serum creatinine >124 micromole per liter (µmol/L) [1.4 milligrams per deciliter (mg/dL)] in women, >133 µmol/L [1.5 mg/dL] in men)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 10 mg LY2944876; 10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: Metformin; Oral; Drug: LY2944876; Administered SC
EXPERIMENTAL: 15 mg LY2944876; 15 mg LY2944876 given SC once weekly for 24 weeks. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: Metformin; Oral; Drug: LY2944876; Administered SC
EXPERIMENTAL: 30 mg LY2944876; 30 mg LY2944876 given SC once weekly for 24 weeks. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: Metformin; Oral; Drug: LY2944876; Administered SC
EXPERIMENTAL: 50 mg LY2944876; 50 mg LY2944876 given SC once weekly for 24 weeks. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: Metformin; Oral; Drug: LY2944876; Administered SC
EXPERIMENTAL: Exenatide extended-release; 2 mg exenatide extended-release given SC once weekly for 24 weeks. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: Metformin; Oral; Drug: Exenatide extended-release; Administered SC
PLACEBO_COMPARATOR: Placebo; Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: Placebo; Administered SC; Drug: Metformin; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c at Week 24	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Baseline, Week 24
Percent Change From Baseline in Body Weight		Baseline, Week 12; Baseline, Week 24
Change From Baseline in Fasting Blood Glucose	Least square means (LSM) was calculated from mixed-effects model with repeated measures (MMRM) analysis using restricted maximum likelihood (REML) with metformin use, baseline body mass index (BMI) category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect.	Baseline, Week 12; Baseline, Week 24
Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	SMBG 7-point profiles were measured at morning pre-meal, morning 2 hours post-meal, mid-day pre-meal, mid-day 2 hours post-meal, evening pre-meal, evening 2 hours post-meal, and at bedtime. LSM were calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect.	Baseline, Week (Wk) 12; Baseline, Week 24
Change From Baseline in Lipids	Change from baseline in high-density lipoprotein cholesterol (HDL-C), total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C). LSM was calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant an a random effect.	Baseline, Week 24
Change From Baseline in Fasting Fibroblast Growth Factor 21	LSM was calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.	Baseline, Week 12; Baseline, Week 24
Percentage of Participants Requiring Rescue Therapy	Participants who received rescue medication with non-study antihyperglycemic medications or change their stable dose of metformin.	Baseline through Therapy Completion (Week 24)
Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Percentage of participants developing anti-drug antibodies to LY2944876.	Week 12 and Week 24
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876	Evaluable pharmacokinetic concentrations from the specified timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.	Baseline, Week 8, Week 12, Week 16, Week 20, Week 24
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876	Evaluable pharmacokinetic concentrations from the specified timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.	Baseline, Week 8, Week 12, Week 16, Week 20, Week 24
Change From Baseline in Adiponectin Levels	LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.	Baseline, Week 12; Baseline, Week 24
Change From Baseline in Beta-Hydroxy Butyrate Levels	LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.	Baseline, Week 12; Baseline, Week 24
Change From Baseline in Glucagon Levels	LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.	Baseline, Week 12; Baseline, Week 24
Change From Baseline in Insulin Levels	LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.	Baseline, Week 12; Baseline, Week 24

Collaborators and Investigators

• Sponsor: OPKO Health, Inc.

Publications and helpful links

General Publications

• Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (ACTUAL): August 1, 2015
• Study Completion (ACTUAL): October 1, 2015

Study Registration Dates

• First Submitted: April 17, 2014
• First Submitted That Met QC Criteria: April 17, 2014
• First Posted (ESTIMATE): April 22, 2014

Study Record Updates

• Last Update Posted (ACTUAL): May 27, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Weight loss
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Metformin; Exenatide
• Other Study ID Numbers: 15062; 2013-003552-21 (EUDRACT_NUMBER); I7I-MC-XNAA (OTHER: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.