A Study in Participants With Type 2 Diabetes Mellitus (AWARD-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01064687
First received: February 5, 2010
Last updated: January 15, 2015
Last verified: January 2015
  Purpose

The purpose of this study is to determine if LY2189265 is effective and safe in reducing hemoglobin A1c (HbA1c), as compared to placebo (no medicine), or exenatide in participants with Type 2 Diabetes. The participants must also be taking metformin and pioglitazone.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: LY2189265
Drug: Exenatide
Drug: Placebo
Drug: Metformin
Drug: Pioglitazone
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 Randomized, Placebo-Controlled Comparison of the Effects of Two Doses of LY2189265 or Exenatide on Glycemic Control in Patients With Type 2 Diabetes on Stable Doses of Metformin and Pioglitazone (AWARD-1: Assessment of Weekly Administration of LY2189265 in Diabetes-1)

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline to 26 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: No ]
    Least squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.


Secondary Outcome Measures:
  • Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
    Least squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.

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

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

  • Change From Baseline to 26 Weeks on Body Mass Index (BMI) [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: No ]
    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 to 52 Weeks on Body Mass Index (BMI) [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
    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 to 26 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: Yes ]
    The SMPG data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. Least squares (LS) means of the mean of the 8 time points (daily mean) were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate.

  • Change From Baseline to 52 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: Yes ]
    The SMPG data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. Least squares (LS) means of the mean of the 8 time points (daily mean) were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate.

  • Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 26 Weeks [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: Yes ]
    The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a logistic regression model with baseline, country, and treatment as factors included in the model.

  • Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 52 Weeks [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: Yes ]
    The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a logistic regression model with baseline, country, and treatment as factors included in the model.

  • Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: Yes ]
    The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-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 populations were set at 100%. 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 to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: Yes ]
    The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-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 populations were set at 100%. 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 to 26 Weeks in the EuroQol 5 [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: No ]
    The European Quality of Life - 5 dimensions (EQ-5D) questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part of the questionnaire consists of a 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). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) and adjusted by treatment, country, and baseline.

  • Change From Baseline to 52 Weeks in the EuroQol 5 [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
    The European Quality of Life - 5 dimensions (EQ-5D) questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part of the questionnaire consists of a 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). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) and adjusted by treatment, country, and baseline.

  • Change From Baseline to 26 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Version [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: No ]
    The Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) is used to assess participant treatment satisfaction at each study visit. The questionnaire consists of 8 items, 6 of which (1, and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. Scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from 0 (very dissatisfied) to 36 (very satisfied). The DTSQ change version (DTSQc) was not collected at 26 weeks. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline score as a covariate.

  • Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
    The Diabetes Treatment Satisfaction Questionnaire status (DTSQs) and change (DTSQc) versions are used to assess participant treatment satisfaction at each study visit and relative change in satisfaction from baseline, respectively. Both questionnaires consist of 8 items, 6 of which (1, and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. The change version has the same 8 items as the status version with a small alteration of the wording of Item 7. Scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from 0 (very dissatisfied) to 36 (very satisfied) for the DTSQs and from -18 (much less satisfied) to +18 (much more satisfied) for the DTSQc. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline score as a covariate.

  • Change From Baseline to 26 Weeks in the Impact of Weight on Activities of Daily Living [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: No ]
    The Impact of Weight on Activities of Daily Living (renamed the Ability to Perform Physical Activities of Daily Living [APPADL]) questionnaire contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = "not at all difficult" and 1 = "unable to do". The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.

  • Change From Baseline to 52 Weeks in the Impact of Weight on Activities of Daily Living [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
    The Impact of Weight on Activities of Daily Living (renamed the Ability to Perform Physical Activities of Daily Living [APPADL]) questionnaire contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = "not at all difficult" and 1 = "unable to do". The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.

  • Change From Baseline to 26 Weeks on the Impact of Weight on Self-Perception [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: No ]
    The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.

  • Change From Baseline to 52 Weeks on the Impact of Weight on Self-Perception [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
    The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.

  • Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks [ Time Frame: Baseline through 52 weeks ] [ Designated as safety issue: Yes ]
    Information on cardiovascular (CV) risk factors was collected at baseline. Data on any new CV event was prospectively collected using a CV event electronic case report form. At prespecified visits, participants were asked about any new CV event since the previous inquiry. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by an external committee of physicians with cardiology expertise. Nonfatal cardiovascular AEs to be adjudicated included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions, and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with CV events confirmed by adjudication is summarized cumulatively at 52 weeks. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module.

  • Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval [ Time Frame: Baseline, 26 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.

  • Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval [ Time Frame: Baseline, 52 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.

  • Change in Baseline to 26 Weeks on Pulse Rate [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: Yes ]
    Seated pulse rate was 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 in Baseline to 52 Weeks on Pulse Rate [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: Yes ]
    Seated pulse rate was 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 to 26 Weeks on Blood Pressure [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: Yes ]
    Seated systolic blood pressure (SBP) and seated 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 to 52 Weeks on Blood Pressure [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: Yes ]
    Seated systolic blood pressure (SBP) and seated 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.

  • Number of Participants With Adjudicated Pancreatitis at 26 Weeks [ Time Frame: Baseline through 26 weeks ] [ Designated as safety issue: Yes ]
    The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26 weeks. 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 Pancreatitis at 52 Weeks [ Time Frame: Baseline through 52 weeks ] [ Designated as safety issue: Yes ]
    The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 52 weeks, with the exception of the Placebo/1.5 mg LY2189265 and Placebo/0.75 mg LY2189265 treatment groups, which include only participants with confirmed pancreatitis during treatment with LY2189265 (26 weeks through 52 weeks). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Change From Baseline to 26 Weeks on Pancreatic Enzymes [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: Yes ]
    Amylase (total and pancreas-derived) and lipase concentrations were measured.

  • Change From Baseline to 52 Weeks on Pancreatic Enzymes [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: Yes ]
    Amylase (total and pancreas-derived) and lipase concentrations were measured.

  • Change From Baseline to 26 Weeks on Serum Calcitonin [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: Yes ]
  • Change From Baseline to 52 Weeks on Serum Calcitonin [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: Yes ]
  • Number of Self-reported Hypoglycemic Events at 26 Weeks [ Time Frame: Baseline through 26 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of 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 less than or equal to 3.9 millimoles/liter [mmol/L]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Number of Self-reported Hypoglycemic Events at 52 Weeks [ Time Frame: Baseline through 52 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of 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 less than or equal to 3.9 millimoles/liter [mmol/L]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events is summarized cumulatively at 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Rate of Self-reported Hypoglycemic Events at 26 Weeks [ Time Frame: Baseline through 26 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of 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 equal to or less than 3.9 millimoles/liter [mmol/L]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of equal to or less than 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Rate of Self-reported Hypoglycemic Events at 52 Weeks [ Time Frame: Baseline through 52 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of 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 equal to or less than millimoles/liter [mmol/L]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of equal to or less than 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 26 Weeks [ Time Frame: Baseline through 26 weeks ] [ Designated as safety issue: Yes ]
    Rescue therapy was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period. Time to start first new glucose-lowering intervention due to hyperglycemia ("rescue therapy") was analyzed between the groups using the semi-parametric proportional hazard regression model with treatment group and country as fixed effects and baseline glycosylated hemoglobin (HbA1c) as a covariate.

  • Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 52 Weeks [ Time Frame: Baseline through 52 weeks ] [ Designated as safety issue: Yes ]
    Rescue therapy was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period. Time to start first new glucose-lowering intervention due to hyperglycemia ("rescue therapy") was analyzed between the groups using the semi-parametric proportional hazard regression model with treatment group and country as fixed effects and baseline glycosylated hemoglobin (HbA1c) as a covariate.

  • Number of Participants With LY2189265 Antibodies at 26 Weeks [ Time Frame: Baseline through 26 weeks ] [ Designated as safety issue: Yes ]
    LY2189265 (Dulaglutide) anti-drug antibodies (ADA) were assessed. The number of participants with initial postbaseline detection of treatment emergent (defined as a 4-fold increase in the ADA titer from baseline) LY2189265 ADA were summarized.

  • Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug [ Time Frame: 26 weeks through 52 weeks and 53 weeks through 4 weeks after last dose ] [ Designated as safety issue: Yes ]
    LY2189265 (Dulaglutide) anti-drug antibodies (ADA) were assessed. The number of participants with initial postbaseline detection of treatment emergent (defined as a 4-fold increase in the ADA titer from baseline) LY2189265 ADA were summarized.

  • 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 one or more TEAE is summarized cumulatively at 26 weeks. 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 one or more TEAE is summarized cumulatively at 52 weeks, with the exception of the Placebo/1.5 mg LY2189265 and Placebo/0.75 mg LY2189265 treatment groups, which include only TEAEs that occurred during treatment with LY2189265 (26 weeks through 52 weeks). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Change From Baseline to 26 Weeks in Hematological and Biochemical Lab Values [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: Yes ]
  • Change From Baseline to 52 Weeks in Hematological and Biochemical Lab Values [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: Yes ]
  • Change From Baseline to 26 Weeks in N Terminal Pro Brain Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: Area Under the Concentration Curve (AUC) for LY2189265 [ Time Frame: 4 weeks, 13 weeks, 26 weeks, and 52 weeks ] [ Designated as safety issue: No ]
    Evaluable pharmacokinetic concentrations from the 4-week, 13-week, 26-week, and 52-week timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.


Enrollment: 978
Study Start Date: February 2010
Study Completion Date: May 2012
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1.5 mg LY2189265

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks

Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks

Pioglitazone: at least 30 mg/day, oral, for 52 weeks

Drug: LY2189265
Other Name: Dulaglutide
Drug: Metformin Drug: Pioglitazone
Experimental: 0.75 mg LY2189265

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks

Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks

Pioglitazone: at least 30 mg/day, oral, for 52 weeks

Drug: LY2189265
Other Name: Dulaglutide
Drug: Metformin Drug: Pioglitazone
Active Comparator: Exenatide

Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks

Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks

Pioglitazone: at least 30 mg/day, oral, for 52 weeks

Drug: Exenatide Drug: Metformin Drug: Pioglitazone
Placebo Comparator: Placebo

Placebo: subcutaneous (SC), once weekly for 26 weeks

LY2189265 (Dulaglutide): After 26 weeks, participants were randomized to receive either 0.75 milligrams (mg) or 1.5 mg, SC, once weekly for an additional 26 weeks (from week 26 through week 52).

Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks

Pioglitazone: at least 30 mg/day, oral, for 52 weeks

Drug: LY2189265
Other Name: Dulaglutide
Drug: Placebo Drug: Metformin Drug: Pioglitazone

Detailed Description:

During the study, if a participant developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, the participant received additional therapeutic intervention or initiation of an alternative antihyperglycemic medication following study drug discontinuation (rescue therapy). Participants who received rescue therapy were included in the analysis population, but only measurements obtained prior to the beginning of rescue therapy were included in specified analyses.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 Diabetes (T2D) not well controlled on 1, 2, or 3 oral antidiabetic medications

    1. Glycosylated hemoglobin (HbA1c) greater than or equal to 7 and less than or equal to 11 if taking 1 oral antidiabetic medication
    2. HbA1c greater than or equal to 7 and less than or equal to 10 if on 2 or 3 oral antidiabetic medications
  • Able to tolerate minimum dose of 1500 milligrams (mg) metformin a day and 30 mg pioglitazone per day.
  • Willing to inject subcutaneous (SC) medication up to 2 times per day
  • Stable weight for 3 months prior to screening
  • Body mass index (BMI) between 23 and 45 kilograms per meter squared (kg/m^2)
  • Females of child bearing potential must test negative for pregnancy at screening by serum pregnancy test and be willing to use a reliable method of birth control during the study and for 1 month following the last dose of study drug.

Exclusion Criteria:

  • Type 1 Diabetes
  • HbA1c equal to or less than 6.5 before randomization or at randomization
  • Chronic insulin use
  • Taking drugs to promote weight loss by prescription or over the counter
  • Taking systemic steroids for greater than 14 days except for topical, eye, nasal, or inhaled
  • History of fluid retention or edema
  • History of Heart Failure New York Heart Classification II, III, or IV or acute myocardial infarction or stroke within 2 months of screening
  • Gastrointestinal (GI; stomach) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking drugs that directly affect GI motility
  • Hepatitis or liver disease or alanine transaminase (ALT) greater than 2.5 times the upper limit of normal
  • Acute or chronic pancreatitis of any form
  • Renal disease (kidney) with a serum creatinine of greater than or equal to 1.5 milligrams per deciliter (mg/dL) for males and greater than or equal to 1.4 mg/dL for females, or a creatine clearance of less than 60 milliliters per minute (mL/min)
  • History (includes family) of type 2A or 2B Multiple Endocrine Neoplasia (MEN 2A or 2B) or medullary c-cell hyperplasia or thyroid cancer
  • A serum calcitonin greater than or equal to 20 picograms per milliliter (pg/mL) at screening
  • Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis
  • History of or active malignancy except skin or in situ cervical or prostate cancer for within last 5 years
  • Sickle cell, hemolytic anemia, or other hematological condition that may interfere with HbA1c testing
  • Organ transplant except cornea
  • Have enrolled in another clinical trial within the last 30 days
  • Have previously signed an informed consent or participated in a LY2189265 (dulaglutide) study
  • Have taken a glucagon-like peptide 1 (GLP-1) receptor agonist within the 3 months prior to screening
  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: NCT01064687

  Show 89 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01064687     History of Changes
Other Study ID Numbers: 11373, H9X-MC-GBDA
Study First Received: February 5, 2010
Results First Received: October 3, 2014
Last Updated: January 15, 2015
Health Authority: United States: Food and Drug Administration
Mexico: Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Argentina: Ministry of Health
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Korea: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Exenatide
Metformin
Pioglitazone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2015