A Study of LY2189265 in Japanese Patients With Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT01001104
• Recruitment Status: Completed
• First Posted: October 23, 2009
• Results First Posted: September 28, 2015
• Last Update Posted: September 28, 2015
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: October 22, 2009
• First Posted Date: October 23, 2009
• Results First Submitted Date: October 3, 2014
• Results First Posted Date: September 28, 2015
• Last Update Posted Date: September 28, 2015
• Study Start Date: October 2009
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 28, 2015)

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 12 Weeks [ Time Frame: Baseline, 12 weeks ]

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.

• Original Primary Outcome Measures (submitted: October 22, 2009): Change in glycosylated hemoglobin (HbA1c) from baseline to 12 weeks endpoint [ Time Frame: Baseline, 12 weeks ]

Current Secondary Outcome Measures (submitted: August 28, 2015)

• Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c)<7% up to 12 Weeks [ Time Frame: up to 12 weeks ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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).

Original Secondary Outcome Measures (submitted: October 22, 2009)

• Percentage of patients achieving glycosylated hemoglobin (HbA1c) < 7% [ Time Frame: 12 weeks ]
• Percentage of patients achieving glycosylated hemoglobin (HbA1c) < 6.5% [ Time Frame: 12 weeks ]
• Change in fasting blood glucose values (FBG) from baseline to 12 weeks endpoint [ Time Frame: Baseline, 12 weeks ]
• Change in mean daily blood glucose (based on Self monitoring blood glucose) from baseline to 12 weeks endpoint [ Time Frame: Baseline, 12 weeks ]
• Change in total body weight from baseline to 12 weeks endpoint [ Time Frame: Baseline, 12 weeks ]
• Change from baseline in insulin sensitivity (HOMA2-S) using the updated Homeostasis Model Assessment (HOMA2) [ Time Frame: Baseline, 12 weeks ]
• Change from baseline in Beta-cell function (HOMA2-B) using the updated Homeostasis Model Assessment (HOMA2) [ Time Frame: Baseline, 12 weeks ]
• Pharmacokinetics Cmax [ Time Frame: 4 weeks, 8 weeks, 12 weeks ]
• Incidence of Self-reported hypoglycemic episodes [ Time Frame: 4 weeks, 8 weeks, 12 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of LY2189265 in Japanese Patients With Type 2 Diabetes
• Official Title: Assessment of Dose-Dependent Effects of LY2189265 on Glycemic Control in Japanese Patients With Type 2 Diabetes
• Brief Summary: The main purpose of this study is to assess dose-response characteristics in Japanese patients with Type 2 Diabetes taking LY2189265 monotherapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2

Intervention

• Drug: LY2189265
  Administered by subcutaneous (SC) injection, once weekly (QW) for 12 weeks.
• Drug: Placebo
  Administered by SC injection, QW for 12 weeks.

Study Arms

• Experimental: 0.75 mg LY2189265
  Intervention: Drug: LY2189265
• Experimental: 0.5 mg LY2189265
  Intervention: Drug: LY2189265
• Experimental: 0.25 mg LY2189265
  Intervention: Drug: LY2189265
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 6, 2011): 145
• Original Estimated Enrollment (submitted: October 22, 2009): 144
• Actual Study Completion Date: December 2010
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT01001104
• Other Study ID Numbers: 12840; H9X-JE-GBCZ ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: August 2015