Clinical trial NCT01558271: A Study of LY2189265 in Japanese Participants With Type 2 Diabetes Mellitus
Official title: A Phase 3 Study of LY2189265 Monotherapy Compared to Placebo and Liraglutide in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: GLP-1
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-03-20
Enrollment: 492
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to examine the efficacy and safety of once-weekly LY2189265 in participants with type 2 diabetes mellitus who are not taking oral antidiabetic medication.

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 criteria: Inclusion Criteria:

* Participants who have had a diagnosis of type 2 diabetes mellitus before screening.
* Participants who have been Oral Antihyperglycemic Medication (OAM)-naïve (diet and exercise only) or been taking OAM monotherapy except for thiazolidinedione (TZD) and are willing to discontinue this medication. Participants taking OAM monotherapy must complete 8-week washout period prior to randomization.
* Participants who are OAM naïve with a screening glycosylated hemoglobin (HbA1c) value of 7.0% to 10.0% and randomization HbA1c value of 7.0% to 10.0%, or who are taking OAM monotherapy with screening HbA1c value of 6.5% to 9.0% and randomization HbA1c value of 7.0% to 10.0%.
* Participants who have a body mass index (BMI) of 18.5 kilograms per meter squared (kg/m\^2) to 35.0 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 been receiving more than half of the maximum dose of sulfonylureas at screening.
* Participants who have been currently taking insulin or TZD, or have had previous insulin or TZD 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).

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks
timeFrame: Baseline, 26 weeks
Secondary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 52 Weeks
timeFrame: Baseline, 52 weeks
measure: Percentage of Participants Who Achieved HbA1c <=6.5% or <7%
timeFrame: Up to 26 and 52 weeks
measure: Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Change From Baseline in Body Weight at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Change From Baseline in Insulin Sensitivity Using Updated Homeostasis Model Assessment (HOMA 2) at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Change From Baseline in Beta-cell Function Using Updated Homeostasis Model Assessment (HOMA 2) at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Percentage of Participants With Hypoglycemic Episodes
timeFrame: Baseline through 26 weeks and Baseline through 52 weeks
measure: 30-Day Rate of Hypoglycemic Episodes
timeFrame: Baseline through 26 weeks and Baseline through 52 weeks
measure: Number of Participants With Adjudicated Cardiovascular Events at 26 Weeks and 52 Weeks
timeFrame: Baseline through 26 weeks and Baseline through 52 weeks
measure: Change From Baseline in Pulse Rate at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Change From Baseline in Blood Pressure at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Number of Participants With Adjudicated Pancreatitis at 26 Weeks and 52 Weeks
timeFrame: Baseline through 26 weeks and Baseline through 52 weeks
measure: Change From Baseline in Pancreatic Enzymes at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Change From Baseline in Serum Calcitonin at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Number of Participants With Treatment-Emergent LY2189265 Anti-Drug Antibodies (ADAs) at 26 Weeks and 52 Weeks
timeFrame: Baseline through 26 weeks and Baseline through 52 weeks
measure: Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26 Weeks and 52 Weeks
timeFrame: Baseline through 26 weeks and Baseline through 52 weeks
measure: Change From Baseline in Electrocardiogram Parameters at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: 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.
city: Hokkaido
country: Japan
facility: 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.
city: Hyogo
country: Japan
facility: 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.
city: Ibaraki
country: Japan
facility: 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.
city: Ishikawa
country: Japan
facility: 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.
city: Kanagawa
country: Japan
facility: 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.
city: Kumamoto
country: Japan
facility: 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.
city: Miyagi
country: Japan
facility: 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.
city: Nagano
country: Japan
facility: 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.
city: Osaka
country: Japan
facility: 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.
city: Tokyo
country: Japan
facility: 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.
city: Toyama
country: Japan
facility: 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.
city: Yamaguchi
country: Japan
facility: 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.
city: Yokohama
country: Japan
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Iwamoto N, Matsui A, Kazama H, Oura T. Subgroup Analysis Stratified by Baseline Pancreatic beta-cell Function in a Japanese Study of Dulaglutide in Patients with Type 2 Diabetes. Diabetes Ther. 2018 Feb;9(1):383-394. doi: 10.1007/s13300-017-0346-4. Epub 2017 Dec 20.
citation: Suzuki S, Oura T, Takeuchi M, Boye KS. Evaluation of the impact of once weekly dulaglutide on patient-reported outcomes in Japanese patients with type 2 diabetes: comparisons with liraglutide, insulin glargine, and placebo in two randomized studies. Health Qual Life Outcomes. 2017 Jun 12;15(1):123. doi: 10.1186/s12955-017-0696-7.