Efficacy and Safety of Exenatide in Japanese Patients With Type 2 Diabetes Who Are Treated With Oral Antidiabetic(s)

Efficacy and Safety of LY2148568 in Japanese Patients With Type 2 Diabetes Who Are Treated With Oral Antidiabetic(s) But Not Well Controlled

This long term, placebo-controlled trial is intended to assess the efficacy and safety of exenatide, dosed twice a day, in Japanese patients with Type 2 Diabetes who are treated with oral antidiabetic(s) but not well controlled.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: exenatide; Drug: exenatide; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan
    • Research Site
  • Fukuoka, Japan
    • Research Site
  • Fukushima, Japan
    • Research Site
  • Hyogo, Japan
    • Research Site
  • Ibaragi, Japan
    • Research Site
  • Kanagawa, Japan
    • Research Site
  • Kumamoto, Japan
    • Research Site
  • Kyoto, Japan
    • Research Site
  • Nagano, Japan
    • Research Site
  • Oita, Japan
    • Research Site
  • Osaka, Japan
    • Research Site
  • Tokyo, Japan
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with type 2 diabetes.
• Has been treated by sulfonylurea (SU) alone, SU and biguanide, or SU and thiazolidinedione for at least 90 days prior to study start. In a patient receiving SU alone, the dose must be within the dose range from maximum maintenance dose to maximum approved dose. The patients with concomitant use of alpha glucosidase inhibitors (acarbose, voglibose or miglitol) or meglitinide derivatives (mitiglinide or nateglinide) can be included in this study, but these drugs must be discontinued at study start.
• Have HbA1c 7.0% to 10% at study start.
• Have a body weight >=50 kg.

Exclusion Criteria:

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Have participated in this study previously or any other study using exenatide or glucagon-like peptide-1 (GLP-1) analogs within the last 90 days.
• Have been treated with any exogenous insulin within 90 days before study start.
• Have been continuously treated with any drug that directly affects gastrointestinal motility for more than a total of 21 days in the 90 days prior to study start.
• The combination therapy of sulfonylurea, biguanide and thiazolidinedione is not allowed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: exenatide; subcutaneous injection, 5mcg, twice a day; Other Names: Byetta; LY2148568; Drug: exenatide; subcutaneous injection, 10mcg, twice a day; Other Names: Byetta; LY2148568
Experimental: 2	Drug: exenatide; subcutaneous injection, 5mcg, twice a day; Other Names: Byetta; LY2148568; Drug: exenatide; subcutaneous injection, 10mcg, twice a day; Other Names: Byetta; LY2148568
Placebo Comparator: 3	Drug: placebo; subcutaneous injection, volume equivalent to 5mcg or 10mcg exenatide, twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 24	Change in HbA1c from baseline following 24 weeks of treatment (i.e., HbA1c at week 24 minus HbA1c at week 0)	baseline, 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Achieving HbA1c < 7.0%	Percentage of subjects whose HbA1c was >=7.0% at baseline who achieved an HbA1c < 7.0% at endpoint (i.e., number of eligible subjects who achieved HbA1c < 7.0% divided by total number of eligible subjects times 100)	24 weeks
Percentage of Patients Achieving HbA1c < 6.5%	Percentage of subjects whose HbA1c was >=6.5% at baseline who achieved an HbA1c < 6.5% at endpoint (i.e., number of eligible subjects who achieved HbA1c < 6.5% divided by total number of eligible subjects times 100)	24 weeks
Change in Fasting Blood Glucose	Change in fasting blood glucose from baseline to endpoint (i.e., fasting blood glucose at week 24 minus fasting blood glucose at week 0)	baseline, week 24
Change in Body Weight	Change in body weight form baseline to endpoint (i.e., body weight at week 24 minus body weight at week 0)	baseline, week 24
Change in Total Cholesterol	Change in total cholesterol from baseline to endpoint (i.e., total cholesterol at week 24 minus total cholesterol at week 0)	baseline, week 24
Change in Low Density Lipoprotein Cholesterol (LDL-C)	Change in LDL-C from baseline to endpoint (i.e., LDL-C at week 24 minus LDL-C at week 0)	baseline, week 24
Change in High Density Lipoprotein Cholesterol (HDL-C)	Change in HDL-C from baseline to endpoint (i.e., HDL-C at week 24 minus HDL-C at week 0)	baseline, week 24
Change in Triglycerides	Change in triglycerides from baseline to endpoint (i.e., triglycerides at week 24 minus triglycerides at week 0)	baseline, week 24
Change in Waist Size	Change in waist size from baseline to endpoint (i.e., waist size at week 24 minus waist size at week 0)	baseline, week 24
Change in Waist-to-hip Ratio	Change in waist-to-hip ratio from baseline to endpoint (i.e., waist-to-hip ratio at week 24 minus waist-to-hip ratio at week 0). Waist-to-hip ratio is waist circumference divided by hip circumference.	baseline, week 24
7 Point Self-monitored Blood Glucose (SMBG) Profiles at Baseline and Week 24	Self-monitored blood glucose at 7 different time points during the day (glucose measurements before and 2 hours after the start of the morning, midday, and evening meals, and at bedtime).	baseline, week 24
Change in Homeostasis Model Assessment - Beta Cell Function (HOMA-B)	Change in HOMA-B from baseline to endpoint (i.e., HOMA-B at week 24 minus HOMA-B at week 0). HOMA-B is a measurement of beta cell function.	baseline, week 24
Change in Homeostasis Model Assessment - Insulin Resistance (HOMA-R)	Change in HOMA-R from baseline to endpoint (i.e., HOMA-R at week 24 minus HOMA-R at week 0). HOMA-R is a measurement of insulin resistance.	baseline, week 24
Change in Serum Insulin	Change in serum insulin from baseline to endpoint (i.e., serum insulin at week 24 minus serum insulin at week 0)	baseline, week 24
Change in C-peptide	Change in C-peptide from baseline to endpoint (i.e., C-peptide at week 24 minus C-peptide at week 0)	baseline, week 24
Change in 1,5-anhydroglucitol	Change in 1,5-anhydroglucitol from baseline to endpoint (i.e., 1,5-anhydroglucitol at week 24 minus 1,5-anhydroglucitol at week 0)	baseline, week 24

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567.
• Kadowaki T, Namba M, Imaoka T, Yamamura A, Goto W, Boardman MK, Sowa H. Improved glycemic control and reduced bodyweight with exenatide: A double-blind, randomized, phase 3 study in Japanese patients with suboptimally controlled type 2 diabetes over 24 weeks. J Diabetes Investig. 2011 Jun 5;2(3):210-7. doi: 10.1111/j.2040-1124.2010.00084.x.
• Inagaki N, Ueki K, Yamamura A, Saito H, Imaoka T. Long-term safety and efficacy of exenatide twice daily in Japanese patients with suboptimally controlled type 2 diabetes. J Diabetes Investig. 2011 Nov 30;2(6):448-56. doi: 10.1111/j.2040-1124.2011.00137.x.

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: December 18, 2007
• First Submitted That Met QC Criteria: December 18, 2007
• First Posted (Estimate): December 20, 2007

Study Record Updates

• Last Update Posted (Estimate): April 9, 2015
• Last Update Submitted That Met QC Criteria: March 20, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: diabetes; exenatide; LY2148568; Lilly; Amylin; Byetta
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: H8O-JE-GWBB