A Study to Compare a New Drug for Type 2 Diabetes to Placebo and to a Treatment Already Available for Type 2 Diabetes
- Conditions
- Diabetes Mellitus, Type 2
- Interventions
- Registration Number
- NCT02119819
- Lead Sponsor
- OPKO Health, Inc.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 420
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Exenatide extended-release 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. 15 mg LY2944876 Metformin 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. Placebo 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. 50 mg LY2944876 Metformin 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. Exenatide extended-release Metformin 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. 10 mg LY2944876 Metformin 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. 15 mg LY2944876 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. 10 mg LY2944876 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. 30 mg LY2944876 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. 50 mg LY2944876 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. 30 mg LY2944876 Metformin 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. Placebo Metformin 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 Baseline, Week 12 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
- Secondary Outcome Measures
Name Time Method Change From Baseline in HbA1c at Week 24 Baseline, Week 24 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Percent Change From Baseline in Body Weight Baseline, Week 12; Baseline, Week 24 Change From Baseline in Fasting Blood Glucose Baseline, Week 12; Baseline, Week 24 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.
Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values Baseline, Week (Wk) 12; Baseline, Week 24 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.
Change From Baseline in Lipids Baseline, Week 24 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.
Change From Baseline in Fasting Fibroblast Growth Factor 21 Baseline, Week 12; Baseline, Week 24 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.
Percentage of Participants Requiring Rescue Therapy Baseline through Therapy Completion (Week 24) Participants who received rescue medication with non-study antihyperglycemic medications or change their stable dose of metformin.
Percentage of Participants Developing Anti-Drug Antibodies to LY2944876 Week 12 and Week 24 Percentage of participants developing anti-drug antibodies to LY2944876.
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876 Baseline, Week 8, Week 12, Week 16, Week 20, Week 24 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.
Change From Baseline in Adiponectin Levels Baseline, Week 12; Baseline, Week 24 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.
Change From Baseline in Beta-Hydroxy Butyrate Levels Baseline, Week 12; Baseline, Week 24 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.
Change From Baseline in Glucagon Levels Baseline, Week 12; Baseline, Week 24 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.
Change From Baseline in Insulin Levels Baseline, Week 12; Baseline, Week 24 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.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876 Baseline, Week 8, Week 12, Week 16, Week 20, Week 24 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.
Trial Locations
- Locations (34)
Southern New Hampshire Diabetes and Endocrinology
🇺🇸Nashua, New Hampshire, United States
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
Manati Medical Center
🇵🇷Manati, Puerto Rico
American Telemedicine Center
🇵🇷San Juan, Puerto Rico
Meridien Research
🇺🇸Bradenton, Florida, United States
John Muir Physician Network Clinical Research Center
🇺🇸Concord, California, United States
Valley Endocrine, Fresno
🇺🇸Fresno, California, United States
National Research Institute
🇺🇸Los Angeles, California, United States
Rocky Mountain Diabetes and Osteoporosis Center
🇺🇸Idaho Falls, Idaho, United States
Desert Medical Group Inc
🇺🇸Palm Springs, California, United States
Encompass Clinical Research
🇺🇸Spring Valley, California, United States
M & O Clinical Research, LLC
🇺🇸Fort Lauderdale, Florida, United States
Suncoast Clinical Research
🇺🇸New Port Richey, Florida, United States
Clinical Research of Central Florida
🇺🇸Winter Haven, Florida, United States
Compass Research
🇺🇸Oviedo, Florida, United States
University of Hawaii
🇺🇸Honolulu, Hawaii, United States
East West Medical Institute
🇺🇸Honolulu, Hawaii, United States
Iderc, P.L.C.
🇺🇸Des Moines, Iowa, United States
St John's Mercy Medical Center
🇺🇸Saint Louis, Missouri, United States
Mercy Medical Research Institute
🇺🇸Springfield, Missouri, United States
Mercy Health Research
🇺🇸Washington, Missouri, United States
Texas Diabetes and Endocrinology
🇺🇸Austin, Texas, United States
High Point Clinical Trials Center
🇺🇸High Point, North Carolina, United States
The Corvallis Clinic P.C.
🇺🇸Corvallis, Oregon, United States
San Gabriel Clinical Research
🇺🇸Georgetown, Texas, United States
Blair Medical Associates, Inc.
🇺🇸Altoona, Pennsylvania, United States
Dallas Diabetes Endocrine Center
🇺🇸Dallas, Texas, United States
Southwest Health Associates, P.A.
🇺🇸Sugar Land, Texas, United States
Wade Family Medicine
🇺🇸Bountiful, Utah, United States
Lillestol Research LLC
🇺🇸Fargo, North Dakota, United States
Cotton O'Neil Diabetes and Endocrinology Center
🇺🇸Topeka, Kansas, United States
Artemis Institute for Clinical Research
🇺🇸San Diego, California, United States
Oakwell Clinical Research
🇺🇸San Antonio, Texas, United States
Suncoast Research Group, LLC
🇺🇸Miami, Florida, United States