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Study of How Dulaglutide Compares to Placebo in Participants With Type 2 Diabetes Who Are Also on Sulfonylurea Therapy (AWARD-8) (AWARD-8)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01769378
First received: January 14, 2013
Last updated: December 18, 2015
Last verified: December 2015
  Purpose
The purpose of this study is to assess the efficacy and safety of once-weekly dulaglutide compared to placebo in participants with type 2 diabetes who have inadequate glycemic control with sulfonylurea monotherapy.

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Placebo
Drug: Dulaglutide
Drug: Glimepiride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Parallel-Arm, Double-Blinded Study Comparing the Effect of Once-Weekly Dulaglutide With Placebo in Patients With Type 2 Diabetes Mellitus on Sulfonylurea Therapy (AWARD-8: Assessment of Weekly AdministRation of LY2189265 in Diabetes - 8)

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 24 Weeks [ Time Frame: Baseline, 24 Weeks ] [ Designated as safety issue: No ]
    Least Squares Means (LS Means) of the HbA1c change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline HbA1c as covariate, via a Mixed-effects model for repeated measures (MMRM) analysis using restricted maximum likelihood (REML).


Secondary Outcome Measures:
  • Percentage of Participants Who Achieve HbA1c <7.0% and ≤6.5% at 24 Weeks [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    The percentage of participants who achieved the target HbA1c values at endpoint will be analyzed with a repeated logistic regression model (the generalized estimation equation [GEE] model). The model includes country, treatment, visit and treatment interaction and baseline HbA1c as a continuous covariate.

  • Change From Baseline in Fasting Serum Glucose (FSG) at 24 Weeks [ Time Frame: Baseline, 24 Weeks ] [ Designated as safety issue: No ]
    LS Means of the FSG from baseline to primary endpoint was adjusted by fixed effects of treatment, country, baseline HbA1c strata, and baseline FSG as covariate, via Analysis of Covariance Model (ANCOVA) with Last Observation Carried Forward (LOCF).

  • Change From Baseline in Body Weight at 24 Weeks [ Time Frame: Baseline, 24 Weeks ] [ Designated as safety issue: No ]
    LS Means of the body weight change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline body weight as covariate, via a MMRM analysis using REML.

  • Change From Baseline in Body Mass Index (BMI) at 24 Weeks [ Time Frame: Baseline, 24 Weeks ] [ Designated as safety issue: No ]
    LS Means of the BMI change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline BMI as covariate, via a MMRM analysis using REML.

  • Change From Baseline in Mean of All 7-Point Self Monitored Plasma Glucose (SMPG) at 24 Weeks [ Time Frame: Baseline, 24 Weeks ] [ Designated as safety issue: No ]
    LS Means of the SMPG change from baseline to primary endpoint at week 24 was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline SMPG value as covariate, via a MMRM analysis using REML.

  • Number of Participants With Reported and Adjudicated Cardiovascular Events [ Time Frame: Baseline through 24 Weeks, 30-day Follow Up ] [ Designated as safety issue: No ]
    Information on cardiovascular (CV) risk factors was collected at baseline. 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 24 weeks plus 30-day follow up. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module.

  • Number of Participants With Adjudicated Acute Pancreatitis Events [ Time Frame: Baseline through 24 Weeks, 30-day Follow Up ] [ Designated as safety issue: Yes ]
    The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 24 weeks plus 30-day follow up. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  • Change From Baseline in Calcitonin at 24 Weeks [ Time Frame: Baseline, 24 Weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With Self-Reported Events of Hypoglycemia [ Time Frame: Baseline through 24 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 =<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =<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). Percentage is calculated as the number of participants reporting HE each visit/ the total number of participants reporting HE during the entire study treatment period.

  • Rate of HE Adjusted Per 30 Days [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: No ]
    The hypoglycemia rate per 30 days during defined period is calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period*30 days.

  • Percentage of Participants Requiring Additional Intervention for Severe, Persistent Hyperglycemia [ Time Frame: Baseline through 24 Weeks ] [ Designated as safety issue: No ]
    Additional Intervention: 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.

  • Time to Initiation of Additional Intervention for Severe, Persistent Hyperglycemia [ Time Frame: Baseline through 24 Weeks ] [ Designated as safety issue: No ]
    An additional intervention (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.

  • Dulaglutide Anti-Drug Antibodies (ADA) [ Time Frame: Baseline up to 4 Weeks Post-Last Dose of Study Drug ] [ Designated as safety issue: Yes ]
    Number of participants with treatment emergent (TE) dulaglutide anti-drug antibodies from postbaseline to follow up were summarized. A participant is considered to have TE dulaglutide ADA if the participant has at least one titer that is treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.

  • Change From Baseline in Lipase [ Time Frame: Baseline, 24 Weeks ] [ Designated as safety issue: No ]
    A summary of changes in lipase evaluation from baseline to endpoint.

  • Change From Baseline in Amylase [ Time Frame: Baseline, 24 Weeks ] [ Designated as safety issue: No ]
    A summary of changes in amylase evaluation from baseline to endpoint.


Enrollment: 300
Study Start Date: January 2013
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo administered subcutaneously (SQ) once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Drug: Placebo
Administered SQ
Drug: Glimepiride
Administered PO
Experimental: Dulaglutide
Dulaglutide 1.5 milligram (mg) administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Drug: Dulaglutide
Administered SQ
Other Name: LY2189265
Drug: Glimepiride
Administered PO

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes mellitus
  • Stable dose of sulfonylurea that is at least 50% of the maximum approved dose per the local label for at least 3 months prior to the first study visit
  • Have an HbA1c value of ≥7.5% and ≤9.5%, as determined by the central laboratory draw performed at the first study visit
  • Accept continued treatment with sulfonylurea therapy, throughout the trial, as required per protocol
  • Men and nonpregnant women aged ≥18 years
  • Stable weight (±5%) ≥3 months prior to screening
  • Body Mass Index (BMI) ≤45 kilograms per square meter (kg/m^2)

Exclusion Criteria:

  • Have type 1 diabetes mellitus
  • Have been treated with ANY other antihyperglycemic medications (other than sulfonylurea) at the time of the first study visit or within 3 months prior to the first study visit
  • Have used insulin therapy (outside of pregnancy) any time in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 weeks; any insulin within 3 months prior to the first study visit is exclusionary
  • Have been treated with drugs that promote weight loss within 3 months prior to the first study visit
  • Are receiving chronic (>14 days) systemic glucocorticoid therapy or have received such therapy within the 4 weeks immediately prior to the first study visit
  • Have had any of the following Cardiovascular (CV) conditions within 2 months prior to the first study visit: acute myocardial infarction, New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident
  • Have a known clinically significant gastric emptying abnormality (eg, severe diabetic gastroparesis or gastric outlet obstruction) or have undergone gastric bypass (bariatric) surgery or restrictive bariatric surgery
  • Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or alanine transaminase level >2.5 times the upper limit of normal
  • Have a history of chronic pancreatitis or acute idiopathic pancreatitis, or were diagnosed with any type of acute pancreatitis within the 3 month period prior to the first study visit
  • Have an estimated glomerular filtration rate [eGFR] <30 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2), calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation as determined by the central laboratory at the first study visit
  • Have any self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B) in the absence of known C-cell hyperplasia (this exclusion includes those participants with a family history of MEN 2A or 2B, whose family history for the syndrome is Rearranged during Transfection (RET) negative; the only exception for this exclusion will be for participants whose family members with MEN 2A or 2B have a known RET mutation and the potential participant for the study is negative for that RET mutation)
  • Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, carcinoma (including sporadic, familial or part of MEN 2A or 2B syndrome)
  • Have a serum calcitonin ≥20 picogram per milliliter (pg/mL) as determined by the central laboratory at the first study visit
  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: NCT01769378

  Show 31 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

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01769378     History of Changes
Other Study ID Numbers: 13193  H9X-MC-GBDG 
Study First Received: January 14, 2013
Results First Received: September 14, 2015
Last Updated: December 18, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Brazil: Ministry of Health
Mexico: Ministry of Health
South Africa: Medicines Control Council
Slovenia: Agency for Medicinal Products - Ministry of Health
Croatia: Agency for Medicinal Product and Medical Devices
Austria: Austrian Medicines and Medical Devices Agency
Romania: National Agency for Medicines and Medical Devices

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Dulaglutide
Glimepiride
Immunoglobulin Fc Fragments
Hypoglycemic Agents
Physiological Effects of Drugs
Immunologic Factors
Anti-Arrhythmia Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 30, 2016