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A Study of LY2189265 in Japanese Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01001104
First received: October 22, 2009
Last updated: August 28, 2015
Last verified: August 2015
  Purpose
The main purpose of this study is to assess dose-response characteristics in Japanese patients with Type 2 Diabetes taking LY2189265 monotherapy.

Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: LY2189265
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Assessment of Dose-Dependent Effects of LY2189265 on Glycemic Control in Japanese Patients With Type 2 Diabetes

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 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    Change in HbA1c from baseline following 12 weeks of therapy (that is, HbA1c at week 12 minus HbA1c at baseline). Changes in HbA1c were analyzed by a mixed model repeated measures (MMRM) model that included dose, pre-study therapy, body mass index (BMI) group at baseline, baseline value, visit, and dose*visit, where the participant was treated as a random effect.


Secondary Outcome Measures:
  • Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c)<7% up to 12 Weeks [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]
    Percentage of participants who achieved HbA1c<7% up to the 12-week endpoint.

  • Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c)<6.5% up to 12 Weeks [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]
    Percentage of participants achieving HbA1c<6.5% up to the 12-week endpoint.

  • Change From Baseline in Fasting Blood Glucose (FBG) Values to 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    Change in FBG following 12 weeks of therapy (that is, FBG at week 12 minus FBG at baseline). The change in FBG was analyzed using a mixed model repeated measures (MMRM) model that included dose, pre-study therapy, body mass index (BMI) group at baseline, baseline value, visit, and dose*visit, where the participant was treated as a random effect.

  • Change From Baseline in the Mean Daily Blood Glucose (Based on Self-Monitoring Blood Glucose [SMBG]) at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    SMBG levels were measured at the following 7 timepoints during the day: fasting prebreakfast, 2 hours postbreakfast, prior to lunch, 2 hours postlunch, prior to dinner, 2 hours postdinner, and prior to bed. The change in mean daily blood glucose was analyzed by a mixed model repeated measures (MMRM) model that included dose, pre-study therapy, body mass index (BMI) group at baseline, baseline value, and dose*visit, where the participant was treated as a random effect.

  • Change From Baseline in Total Body Weight at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    Changes in body weight were analyzed by a mixed model repeated measures (MMRM) model that included dose, pre-study therapy, body mass index (BMI) group at baseline, baseline value, visit, and dose*visit, where the participant was treated as a random effect.

  • Change From Baseline in Insulin Sensitivity Using the Updated Homeostasis Model Assessment Insulin Sensitivity (HOMA2-S) at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    HOMA2-S is an estimated insulin sensitivity based on updated HOMA2 model. The HOMA2 model is a computer model that estimates insulin sensitivity (%S) as percentages of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. Changes in HOMA2-S were analyzed by a mixed model repeated measures (MMRM) model that included dose, pre-study therapy, body mass index (BMI) group at baseline, baseline value, visit, and dose*visit, where the participant was treated as a random effect.

  • Change From Baseline in Beta-Cell Function Using the Updated Homeostasis Model Assessment Beta-Cell Function (HOMA2-B) at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    HOMA2-B is an estimated steady state beta cell function based on updated HOMA2 model. The HOMA2 model estimates steady state pancreatic beta cell function (%B) as a percentage of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. Changes in HOMA2-B were analyzed by a mixed model repeated measures (MMRM) model that included dose, pre-study therapy, body mass index (BMI) group at baseline, baseline value, visit, and dose*visit, where the participant was treated as a random effect.

  • Steady-State Concentrations of LY2189265 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Evaluable pharmacokinetics (PK) concentrations from all sampling time-points were combined and utilized in a population approach to determine the population mean estimate and standard deviation at 12 weeks. The model predicted LY2189265 steady state concentrations in each dose level were calculated as estimated area under the curve (AUC)/dosing period of 168 hours. The models and model parameters were described by nonlinear, mixed-effects regression modeling (NONMEM) using the program NONMEM 7®.

  • Percentage of Participants With Self-Reported Hypoglycemic Episodes During the 12-week Treatment Period [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Assessed the percentage of participants who reported a hypoglycemic episode during the 12-week treatment period. Hypoglycemia was defined as a measured plasma glucose level of ≤70 milligrams per deciliter (mg/dL) or ≤3.9 millimoles per liter (mmol/L).


Enrollment: 145
Study Start Date: October 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 0.75 mg LY2189265 Drug: LY2189265
Administered by subcutaneous (SC) injection, once weekly (QW) for 12 weeks.
Experimental: 0.5 mg LY2189265 Drug: LY2189265
Administered by subcutaneous (SC) injection, once weekly (QW) for 12 weeks.
Experimental: 0.25 mg LY2189265 Drug: LY2189265
Administered by subcutaneous (SC) injection, once weekly (QW) for 12 weeks.
Placebo Comparator: Placebo Drug: Placebo
Administered by SC injection, QW for 12 weeks.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Japanese patients with type 2 diabetes with a body mass index (BMI)≥18.5 kilograms per square meter (kg/m^2) but <40.0 kg/m^2.
  • Patients who are oral antidiabetic drug (OAD) naïve or are taking OAD monotherapy except for a dipeptidyl peptidase-4 inhibitor (DPP-IV) and are willing to discontinue their OAD.
  • Patients who are OAD naïve with screening glycosylated hemoglobin (HbA1c) value of 7.0% to 9.5% and randomization HbA1c value of 7.0% to 9.5%, or who are taking OAD monotherapy with screening HbA1c value of 6.0% to 8.5% and randomization HbA1c value of 7.0% to 9.5%.
  • Patients who have, in the opinion of the investigator, a stable weight during the 12 weeks prior to screening.

Exclusion Criteria:

  • Patients who are currently taking prescription medications to promote weight loss
  • Patients who are receiving chronic systemic glucocorticoid therapy, or have received such therapy within 4 weeks immediately prior to screening.
  • Patients who have a known clinically significant gastrointestinal disorder, have undergone excision of all or any part of the gastrointestinal tract, have undergone gastric bypass surgery for treatment of obesity, or chronically take drugs that directly influence gastrointestinal motility.
  • Patients who have poorly controlled hypertension, renal artery stenosis, or evidence of labile blood pressure including symptomatic postural hypotension.
  • Patients who have obvious clinical signs or symptoms of pancreatitis, a history of chronic pancreatitis or acute pancreatitis. Patients who have amylase and/or lipase of 1.5 times or more the upper limit of the reference range.
  • Have a family history, obvious clinical signs, or symptoms of medullary carcinoma of thyroid.
  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: NCT01001104

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.
Chiba, Japan, 276-0049
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, 359-1161
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.
Kochi, Japan, 781-8555
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, 604-8151
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, 530-0047
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, 171-0021
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 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01001104     History of Changes
Other Study ID Numbers: 12840  H9X-JE-GBCZ 
Study First Received: October 22, 2009
Results First Received: October 3, 2014
Last Updated: August 28, 2015
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Eli Lilly and Company:
Metabolic Diseases
Glucose Metabolism Disorders
Diabetes
GLP-1
Lilly

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Dulaglutide
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 27, 2016