A Study of Dulaglutide in Japanese Participants With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01584232
First received: April 23, 2012
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

The purpose of this trial is to examine the efficacy and safety of once-weekly LY2189265 (dulaglutide) in participants with type 2 diabetes mellitus taking an oral antihyperglycemic medication (OAM).


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: LY2189265
Drug: Insulin glargine
Drug: Sulfonylureas (SU)
Drug: Biguanide (BG)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3 Study of LY2189265 Compared to Insulin Glargine in Patients With Type 2 Diabetes Mellitus on a Sulfonylurea and/or Biguanide

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: No ]
    Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect.


Secondary Outcome Measures:
  • Percentage of Participants Who Achieved Glycosylated Hemoglobin (HbA1c) <=6.5% or <7% at 26 Weeks [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: No ]
    The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a longitudinal logistic regression model with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect.

  • Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: No ]
    Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline FBG as a covariate, and participant as a random effect.

  • Change From Baseline in 8-Point Self-Monitored Blood Glucose (SMBG) at 26 Weeks [ Time Frame: Baseline, Up to 26 weeks ] [ Designated as safety issue: No ]
    Participants were to test and record SMBG concentrations in their study diaries before each meal (breakfast, lunch, and dinner), approximately 2 hours after the start of each meal, at bedtime, and before breakfast the next morning (second pre-morning meal). Least squares (LS) means were calculated using analysis of covariance (ANCOVA) model with treatment, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects and baseline SMBG as a covariate.

  • Change From Baseline in Body Weight at 26 Weeks [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: Yes ]
    Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline body weight as a covariate, and participant as a random effect.

  • Percentage of Participants With Hypoglycemic Episodes [ Time Frame: Baseline through 26 Weeks ] [ Designated as safety issue: Yes ]
    The percentage of participants with hypoglycemic episodes was calculated by dividing the number of participants with at least one hypoglycemic episode over the 26-week treatment period by the total number of participants analyzed, multiplied by 100%. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.


Enrollment: 361
Study Start Date: April 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2189265 + OAM

LY2189265: 0.75 milligrams (mg), administered subcutaneously (SC), once weekly for 26 weeks

Participants were to continue on their stable, pre-study, physician-prescribed dose of oral antihyperglycemic medication (OAM) throughout the study. OAMs included sulfonylureas (SU; glibenclamide, gliclazide, or glimepiride) and/or biguanides (BG; metformin or buformin).

Drug: LY2189265
Other Name: Dulaglutide
Drug: Sulfonylureas (SU) Drug: Biguanide (BG)
Active Comparator: Insulin glargine + OAM

Insulin glargine: dose based on targeting fasting blood glucose ≤110 milligrams per deciliter (mg/dL), administered subcutaneously (SC), once daily for 26 weeks

Participants were to continue on their stable, pre-study, physician-prescribed dose of oral antihyperglycemic medication (OAM) throughout the study. OAMs included sulfonylureas (SU; glibenclamide, gliclazide, or glimepiride) and/or biguanides (BG; metformin or buformin).

Drug: Insulin glargine Drug: Sulfonylureas (SU) Drug: Biguanide (BG)

Detailed Description:

Rescue therapy (defined as alternative antihyperglycemic medication use or dose modification of oral antihyperglycemic medication [OAM]) may have been initiated during the planned treatment period if the participant discontinued study drug or met prespecified thresholds for severe, persistent hyperglycemia. Efficacy data, as well as data for hypoglycemic episodes from participants who permanently discontinued study treatment but switched to another diabetes medication and remained in the study, were censored from the point of initiating new treatment onwards.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants who have had a diagnosis of type 2 diabetes mellitus for at least 6 months before screening
  • Participants who have been taking sulfonylurea (glibenclamide, gliclazide, or glimepiride) and/or biguanide (metformin or buformin). The dose of the drug(s) during the 8 weeks before screening must be stable
  • Participants who have a qualifying glycosylated hemoglobin (HbA1c) value of 7.0% to 10.0% at screening
  • Participants who have a body mass index (BMI) of 18.5 to 35.0 kilograms per meter squared (kg/m^2)

Exclusion Criteria:

  • Participants who have a diagnosis of type 1 diabetes
  • Participants who have previously been treated with any other glucagon-like peptide 1 (GLP-1) analog
  • Participants who have received therapy with an alpha-glucosidase inhibitor (a-GI), thiazolidinedione (TZD), glinide, or dipeptidyl peptidase-IV (DPP-IV) inhibitor within 3 months before screening
  • Participants who have been currently taking insulin or have had previous insulin treatment within 3 months before screening
  • Participants who have obvious clinical signs or symptoms of pancreatitis, a history of chronic pancreatitis, or acute pancreatitis at screening, as determined by the investigator. Participants who have a serum amylase concentration ≥ 3 times the upper limit of the reference range and/or a serum lipase concentration ≥ 2 times the upper limit of the reference range, as determined by the central laboratory at screening
  • Participants who have self or family history of medullary C-cell hyperplasia, focal hyperplasia, or medullary thyroid carcinoma (MTC)
  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: NCT01584232

Locations
Japan
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.
Aichi, Japan, 448-0852
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.
Chiba, Japan, 286-0048
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.
Ehime, Japan, 790-0024
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.
Fukuoka, Japan, 819-0168
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.
Hokkaido, Japan, 0530018
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.
Kagoshima, Japan, 8910401
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.
Kanagawa, Japan, 247-0055
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.
Kumamoto, Japan, 860-0811
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.
Kyoto, Japan, 606-8397
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.
Nagano, Japan, 385-0022
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.
Nagasaki, Japan, 857-1195
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.
Ooita, Japan, 8700039
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.
Osaka, Japan, 598-0048
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.
Tokyo, Japan, 103-0028
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.
Yamaguchi, Japan, 754-0002
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: NCT01584232     History of Changes
Other Study ID Numbers: 14359, H9X-JE-GBDY
Study First Received: April 23, 2012
Results First Received: October 3, 2014
Last Updated: October 14, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Eli Lilly and Company:
Glucagon-like peptide-1 (GLP-1)

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glargine
Insulin
Insulin, Globin Zinc
Insulin, Long-Acting
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014