A Study of LY2189265 in Japanese Patients With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Assessment of Dose-Dependent Effects of LY2189265 on Glycemic Control in Japanese Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01001104
• Other study ID #: 12840
• Secondary ID: H9X-JE-GBCZ
• Status: Completed
• Phase: Phase 2
• First received: October 22, 2009
• Last updated: August 28, 2015
• Start date: October 2009
• Est. completion date: December 2010

Study information

• Verified date: August 2015
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to assess dose-response characteristics in Japanese patients with Type 2 Diabetes taking LY2189265 monotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

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

Locations

Country	Name	City	State
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	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	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	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	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	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

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 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.	Baseline, 12 weeks	No
Secondary	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c)<7% up to 12 Weeks	Percentage of participants who achieved HbA1c<7% up to the 12-week endpoint.	up to 12 weeks	No
Secondary	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c)<6.5% up to 12 Weeks	Percentage of participants achieving HbA1c<6.5% up to the 12-week endpoint.	up to 12 weeks	No
Secondary	Change From Baseline in Fasting Blood Glucose (FBG) Values to 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.	Baseline, 12 weeks	No
Secondary	Change From Baseline in the Mean Daily Blood Glucose (Based on Self-Monitoring Blood Glucose [SMBG]) at 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.	Baseline, 12 weeks	No
Secondary	Change From Baseline in Total Body Weight at 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.	Baseline, 12 weeks	No
Secondary	Change From Baseline in Insulin Sensitivity Using the Updated Homeostasis Model Assessment Insulin Sensitivity (HOMA2-S) at 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.	Baseline, 12 weeks	No
Secondary	Change From Baseline in Beta-Cell Function Using the Updated Homeostasis Model Assessment Beta-Cell Function (HOMA2-B) at 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.	Baseline, 12 weeks	No
Secondary	Steady-State Concentrations of LY2189265	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®.	12 weeks	No
Secondary	Percentage of Participants With Self-Reported Hypoglycemic Episodes During the 12-week Treatment Period	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).	12 weeks	Yes