Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study of LY2189265 Compared to Sitagliptin in Participants With Type 2 Diabetes Mellitus on Metformin

This study has been completed.
Sponsor:
Collaborators:
United BioSource Corporation
Tessella Inc.
Berry Consultants
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00734474
First received: August 12, 2008
Last updated: January 26, 2015
Last verified: January 2015
  Purpose

This is an adaptive dose finding study and a Phase 3 efficacy study to evaluate the effects of once weekly injection of LY2189265 compared to Sitagliptin on glucose by measuring glycosylated hemoglobin (HbA1c) change from baseline after 52 weeks in participants with type 2 diabetes mellitus on Metformin.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: LY2189265
Drug: Sitagliptin
Drug: Placebo solution
Drug: Placebo tablet
Drug: Metformin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2/3, Placebo-Controlled, Efficacy and Safety Study of Once-Weekly, Subcutaneous LY2189265 Compared to Sitagliptin in Patients With Type 2 Diabetes Mellitus on Metformin

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Glycosylated Hemoglobin (HbA1c) Change From Baseline [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
    Least squares (LS) means were calculated using analysis of covariance (ANCOVA) and last observation carried forward (LOCF) imputation with country and treatment as fixed effects and baseline HbA1c as a covariate.


Secondary Outcome Measures:
  • Change From Baseline in Glycosylated Hemoglobin (HbA1c) at the Dose Decision Point [ Time Frame: Baseline up to 27.4 weeks ] [ Designated as safety issue: No ]
    Change from baseline in HbA1c was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the decision point was 27.4 weeks.

  • Glycosylated Hemoglobin (HbA1c) Change From Baseline [ Time Frame: Baseline, 26 weeks, 104 weeks ] [ Designated as safety issue: No ]
    Least squares (LS) means were calculated using analysis of covariance (ANCOVA) and last observation carried forward (LOCF) imputation with country and treatment as fixed effects and baseline HbA1c as a covariate.

  • Durability of Change From Baseline in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline, 13, 26, 52, and 104 weeks ] [ Designated as safety issue: No ]
    Durability of effect on HbA1c was assessed by comparing the differences in mean change from baseline in HbA1c at 1 time point versus an earlier time point. Least squares (LS) means of change from baseline HbA1c data were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

  • Fasting Blood Glucose Change From Baseline [ Time Frame: Baseline, 26, 52, and 104 weeks ] [ Designated as safety issue: No ]
    Least squares (LS) means of change from baseline were calculated using mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

  • Fasting Insulin Change From Baseline [ Time Frame: Baseline, 26, 52, and 104 weeks ] [ Designated as safety issue: No ]
    Least squares (LS) means of change from baseline fasting insulin data were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

  • Change From Baseline in Body Weight at Dose Decision Point [ Time Frame: Baseline up to 27.4 weeks ] [ Designated as safety issue: No ]
    Change from baseline in body weight was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the decision point was 27.4 weeks.

  • Body Weight Change From Baseline [ Time Frame: Baseline, 26, 52, and 104 weeks ] [ Designated as safety issue: Yes ]
    Least squares (LS) means of change from baseline body weight were calculated using analysis of covariance (ANCOVA) and last observation carried forward (LOCF) imputation with country and treatment as fixed effects and baseline as a covariate.

  • Durability of Change From Baseline Body Weight [ Time Frame: Baseline, 13, 26, 52, and 104 weeks ] [ Designated as safety issue: No ]
    Durability of effect on body weight was assessed by comparing the differences in mean change from baseline in body weight at 1 time point versus an earlier time point. Least squares (LS) means of change from baseline body weight data were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

  • Waist Circumference Change From Baseline [ Time Frame: Baseline, 26, 52, and 104 weeks ] [ Designated as safety issue: Yes ]
    Least squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

  • Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5% [ Time Frame: Baseline, 26, 52, and 104 weeks ] [ Designated as safety issue: No ]
    The percentage of participants achieving HbA1c levels <7.0% and ≤6.5% was analyzed using a logistic regression model and last observation carried forward (LOCF) imputation with baseline, country, and treatment as factors included in the model.

  • Incidence of Hypoglycemic Episodes [ Time Frame: Baseline through 26 and 104 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemic episodes (HE) were classified as severe (defined as episodes requiring assistance from another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia and has a plasma glucose level of ≤3.9 millimoles per liter [mmol/L]), asymptomatic (defined as episodes not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of ≤3.9 mmol/L), nocturnal (defined as any episode that occurred between bedtime and waking), or probable symptomatic (defined as episodes during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of participants with self-reported hypoglycemic events is summarized cumulatively.

  • Rate of Hypoglycemic Episodes [ Time Frame: Baseline through 26 and 104 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemic episodes (HE) were classified as severe (defined as episodes requiring assistance from another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia and has a plasma glucose level of ≤3.9 millimoles per liter [mmol/L]), asymptomatic (defined as episodes not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of ≤3.9 mmol/L), nocturnal (defined as any episode that occurred between bedtime and waking), or probable symptomatic (defined as episodes during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of HE is summarized cumulatively.

  • Beta Cell Function and Insulin Sensitivity (HOMA2) [ Time Frame: Baseline, 26, 52, and 104 weeks ] [ Designated as safety issue: No ]
    The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-%B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-%S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S), as percentages of a normal reference population (normal young adults). The normal reference population for both HOMA2-%B and HOMA2-%S were set at 100%. Least squares (LS) means of change from baseline of C-peptide based HOMA2-%B and HOMA2-%S were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

  • Number of Participants With Treatment-emergent Adverse Events at 26 Weeks [ Time Frame: Baseline through 26 weeks ] [ Designated as safety issue: Yes ]
    A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with 1 or more TEAEs is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Number of Participants With Treatment-emergent Adverse Events at 52 Weeks [ Time Frame: Baseline through 52 weeks ] [ Designated as safety issue: Yes ]
    A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with 1 or more TEAEs is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Number of Participants With Treatment-emergent Adverse Events at 104 Weeks [ Time Frame: Baseline through 104 weeks ] [ Designated as safety issue: Yes ]
    A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with 1 or more TEAEs is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks [ Time Frame: Baseline through 26 weeks ] [ Designated as safety issue: Yes ]
    The number of participants with treatment-emergent abnormal laboratory results (defined as abnormalities that first occur after baseline) was summarized cumulatively for alkaline phosphatase, alanine aminotransferase or serum glutamic pyruvic transaminase (ALT/SGPT), amylase (pancreatic and total), aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT), basophils, bilirubin (direct and total), calcitonin, chloride, creatine phosphokinase (CPK), creatinine, creatinine clearance, eosinophils, erythrocytes, gamma glutamyltransferase (GGT), hematocrit, hemoglobin, leukocytes, lipase, lymphocytes, mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), monocytes, neutrophils, platelets, potassium, sodium, urea nitrogen, and urine microalbumin-to-creatinine ratio (UMCR).

  • Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks [ Time Frame: Baseline through 52 weeks ] [ Designated as safety issue: Yes ]
    The number of participants with treatment-emergent abnormal laboratory results (defined as abnormalities that first occur after baseline) was summarized cumulatively for alkaline phosphatase, alanine aminotransferase or serum glutamic pyruvic transaminase (ALT/SGPT), amylase (pancreatic and total), aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT), basophils, bilirubin (direct and total), calcitonin, chloride, creatine phosphokinase (CPK), creatinine, creatinine clearance, eosinophils, erythrocytes, gamma glutamyltransferase (GGT), hematocrit, hemoglobin, leukocytes, lipase, lymphocytes, mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), monocytes, neutrophils, platelets, potassium, sodium, urea nitrogen, and urine microalbumin-to-creatinine ratio (UMCR) .

  • Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks [ Time Frame: Baseline through 104 weeks ] [ Designated as safety issue: Yes ]
    The number of participants with treatment-emergent abnormal laboratory results (defined as abnormalities that first occur after baseline) was summarized cumulatively for alkaline phosphatase, alanine aminotransferase or serum glutamic pyruvic transaminase (ALT/SGPT), amylase (pancreatic and total), aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT), basophils, bilirubin (direct and total), calcitonin, chloride, creatine phosphokinase (CPK), creatinine, creatinine clearance, eosinophils, erythrocytes, gamma glutamyltransferase (GGT), hematocrit, hemoglobin, leukocytes, lipase, lymphocytes, mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), monocytes, neutrophils, platelets, potassium, sodium, urea nitrogen, and urine microalbumin-to-creatinine ratio (UMCR).

  • Number of Participants With Treatment-emergent Abnormal Lipid Tests [ Time Frame: Baseline through 26 and 104 weeks ] [ Designated as safety issue: Yes ]
    The number of participants with treatment-emergent abnormal lipid test (cholesterol, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], and triglycerides [TG]) results (defined as lipid test abnormalities that first occurred after baseline) is summarized cumulatively.

  • Change From Baseline in Pulse Rate at Dose Decision Point [ Time Frame: Baseline up to 27.4 weeks ] [ Designated as safety issue: Yes ]
    Sitting pulse rate was measured at the time that the dose decision was made (dose decision point). Change from baseline in pulse rate was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the decision point was 27.4 weeks.

  • Change From Baseline in Blood Pressure at Dose Decision Point [ Time Frame: Baseline up to 27.4 weeks ] [ Designated as safety issue: Yes ]
    Sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at the dose decision point. Change from baseline in DBP was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the time of the decision point was 27.4 weeks.

  • Change From Baseline in Pulse Rate [ Time Frame: Baseline, 26 weeks, 104 weeks ] [ Designated as safety issue: Yes ]
    Sitting and standing pulse rate were measured. Least squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as covariate.

  • Change From Baseline in Blood Pressure [ Time Frame: Baseline, 26 weeks, 104 weeks ] [ Designated as safety issue: Yes ]
    Sitting and standing systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Least squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

  • Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval [ Time Frame: Baseline, 26 weeks, 104 weeks ] [ Designated as safety issue: Yes ]
    The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

  • Participant-reported Outcomes, Impact of Weight on Quality of Life-Lite (IWQoL-Lite) [ Time Frame: Baseline, 52 weeks, and 104 weeks ] [ Designated as safety issue: No ]
    The Impact of Weight on Quality of Life-Lite (IWQoL-Lite questionnaire) is an obesity-specific, 31-item questionnaire designed to measure the impact of weight on participants' quality of life. Items are scored on a 5-point numeric rating scale where 5 = "always true" and 1 = "never true". Items are summed into 6 scales (physical function [11 items], self-esteem [7 items], sexual life [4 items], public distress [5 items], work [4 items], and total score [31 items]) based on the average for the valid responses on that scale multiplied by the number of items on that scale (rounded to the nearest whole integer). Higher scores indicate lower levels of functioning (negative effects). Scores are linearly transformed to a 0 to 100 scale.

  • Participant-reported Outcomes, EQ-5D [ Time Frame: Baseline, 52 weeks, and 104 weeks ] [ Designated as safety issue: No ]
    The EQ-5D questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts. The first part allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a three level scale of 1-3 (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the UK population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). The second part of the questionnaire consists of a 100-millimeter visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health state).

  • Resource Utilization [ Time Frame: Baseline through 52 and 104 weeks ] [ Designated as safety issue: No ]
    The number of visits to the emergency room (ER) is summarized cumulatively.

  • Pharmacokinetics of LY2189265: Area Under the Concentration-Time Curve [ Time Frame: Baseline through 52 weeks ] [ Designated as safety issue: No ]
    Pharmacokinetic (PK) parameter estimates from LY2189265 concentration data were obtained using a 2-compartment population PK model with first order absorption. Area under the plasma-concentration curve from 0 to 168 hours, steady state (AUC0-168h, ss) of LY2189265 is summarized.

  • Antibodies to LY2189265 [ Time Frame: Baseline through 104 weeks ] [ Designated as safety issue: Yes ]
    The number of participants with postbaseline detection of treatment-emergent antidrug LY2189265 antibodies (ADA) is summarized.


Other Outcome Measures:
  • Number of Participants With Adjudicated Pancreatitis at 104 Weeks [ Time Frame: Baseline through 104 weeks ] [ Designated as safety issue: Yes ]
    The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Number of Participants With Adjudicated Cardiovascular Events at 104 Weeks [ Time Frame: Baseline through 104 weeks ] [ Designated as safety issue: Yes ]
    Data on any new cardiovascular (CV) event was prospectively collected using a CV event electronic case report form. At prespecified visits, participants were asked about any new CV event. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs to be adjudicated include myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with adjudicated CV events is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.


Enrollment: 1202
Study Start Date: August 2008
Study Completion Date: July 2012
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 3.0 mg LY2189265

LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks

Placebo: tablet, administered orally, once daily for up to 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks

Drug: LY2189265
Other Names:
  • Dulaglutide
  • Trulicity
Drug: Placebo tablet Drug: Metformin
Experimental: 2.0 mg LY2189265

LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks

Placebo: tablet, administered orally, once daily for up to 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks

Drug: LY2189265
Other Names:
  • Dulaglutide
  • Trulicity
Drug: Placebo tablet Drug: Metformin
Experimental: 1.5 mg LY2189265

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks

Placebo: tablet, administered orally, once daily for up to 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks

Drug: LY2189265
Other Names:
  • Dulaglutide
  • Trulicity
Drug: Placebo tablet Drug: Metformin
Experimental: 1.0 mg LY2189265

LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks

Placebo: tablet, administered orally, once daily for up to 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks

Drug: LY2189265
Other Names:
  • Dulaglutide
  • Trulicity
Drug: Placebo tablet Drug: Metformin
Experimental: 0.75 mg LY2189265

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks

Placebo: tablet, administered orally, once daily for up to 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks

Drug: LY2189265
Other Names:
  • Dulaglutide
  • Trulicity
Drug: Placebo tablet Drug: Metformin
Experimental: 0.5 mg LY2189265

LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks

Placebo: tablet, administered orally, once daily for up to 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks

Drug: LY2189265
Other Names:
  • Dulaglutide
  • Trulicity
Drug: Placebo tablet Drug: Metformin
Experimental: 0.25 mg LY2189265

LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks

Placebo: tablet, administered orally, once daily for up to 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks

Drug: LY2189265
Other Names:
  • Dulaglutide
  • Trulicity
Drug: Placebo tablet Drug: Metformin
Active Comparator: Sitagliptin

Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks

Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks

Drug: Sitagliptin Drug: Placebo solution Drug: Metformin
Placebo Comparator: Placebo/Sitagliptin (Baseline Through 104 Weeks)

Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks

Placebo: tablet, administered orally, once daily for 26 weeks

Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks

Drug: Placebo solution Drug: Placebo tablet Drug: Metformin

Detailed Description:

This is a double blind study designed to select 1 or 2 LY2189265 doses for evaluation in Phase 3 studies (dose-finding portion) and to evaluate efficacy and safety of selected doses of LY2189265 in comparison to Sitagliptin (100 milligrams) up to 104 weeks and Placebo up to 26 weeks in participants with type 2 diabetes mellitus on Metformin (confirmatory, Phase 3 portion). The primary objective is to show non-inferiority of the higher LY2189265 dose (if 2 doses are selected) to Sitagliptin with respect to change in glycosylated hemoglobin (HbA1c) at 52 weeks. The final endpoint is 104 weeks.

Participants are randomized to receive Placebo, Sitagliptin, or 1 of 7 initial LY2189265 doses until a dose decision is made based on quantitative analysis of the benefits and risks of each LY2189265 dose. A clinical utility index (CUI) that applies predicted values for change from baseline in HbA1c at 12 months and change from baseline in weight, diastolic blood pressure, and pulse rate at 6 months for each LY2189265 dose will be used toward this end. After the dose decision, participants in the selected LY2189265 arms and the comparator arms (Sitagliptin and Placebo/Sitagliptin arms) will continue the study, and additional participants will be randomized to the selected and comparator arms. Regardless of the timing of randomization relative to the dose decision point, all participants in the selected and comparator arms are planned to receive treatment for 104 weeks; participants in the Placebo/Sitagliptin arm will receive Placebo treatment for 26 weeks followed by Sitagliptin 100 mg for 78 weeks for blinding purposes only, and participants in the selected and Sitagliptin arms will receive the same treatment for 104 weeks. All participants will remain blinded to their study treatment throughout the study. Participants in the non-selected arms will discontinue from the study after the dose decision

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diabetes mellitus, type 2, for at least 6 months
  • Treatment regimens: diet and exercise, metformin as monotherapy or in combination with another oral antihyperglycemic medication (OAM), or another OAM as monotherapy. Must be able to tolerate metformin at a dose of at least 1500 milligrams (mg) daily for 6 weeks prior to randomization.
  • Glycosylated hemoglobin (HbA1c) value of ≥7.0% to ≤9.5%, except participants on diet and exercise therapy who must have had HbA1c value of >8.0% to ≤9.5%
  • Body mass index (BMI) between 25 and 40 kilograms per meter squared (kg/m^2), inclusive
  • Stable weight for 3 months prior to screening
  • Females of childbearing potential must test negative for pregnancy and agree to use a reliable birth control method

Exclusion Criteria:

  • Diabetes mellitus, type 1
  • Use of a glucagon-like peptide-1 (GLP-1) analog (for example, exenatide) within 6 months prior to screening or are being treated with insulin
  • Gastric emptying abnormality, history of bariatric surgery, or chronic use of drugs that affect gastrointestinal motility
  • Use of medications to promote weight loss
  • Clinically-relevant cardiovascular event within 6 months prior to screening
  • Poorly controlled hypertension
  • Electrocardiogram (ECG) reading considered outside the normal limits or indicating cardiac disease
  • Liver disease, hepatitis, chronic pancreatitis, idiopathic acute pancreatitis, or alanine transaminase (ALT) levels >3.0 times the upper limit of normal
  • Serum creatinine ≥1.5 milligrams per deciliter (mg/dL) or a creatinine clearance <60 milliliters per minute (mL/minute)
  • Uncontrolled diabetes, defined as >2 episodes of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to study entry.
  • Uncontrolled endocrine or autoimmune abnormality
  • History of a transplanted organ
  • Chronic use of systemic glucocorticoid therapy
  • Active or untreated malignancy
  • Use of central nervous system (CNS) stimulants
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00734474

  Show 99 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
United BioSource Corporation
Tessella Inc.
Berry Consultants
Investigators
Study Chair: 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
  More Information

Additional Information:
No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00734474     History of Changes
Other Study ID Numbers: 11422, H9X-MC-GBCF, CTRI/2009/091/000969
Study First Received: August 12, 2008
Results First Received: October 3, 2014
Last Updated: January 26, 2015
Health Authority: United States: Food and Drug Administration
Brazil: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Mexico: Ministry of Health
Poland: Ministry of Health
Romania: Ministry of Public Health
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan: Department of Health

Keywords provided by Eli Lilly and Company:
Diabetes, type 2 diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on March 03, 2015