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A Study of the Safety and Effectiveness of a R256918 in Patients With Type 2 Diabetes

Phase 2
Completed
Conditions
Diabetes Mellitus
Endocrine System Diseases
Nutritional and Metabolic Diseases
Diabetes Mellitus, Type 2
Interventions
Drug: Placebo
Other: Dietary Counseling
Registration Number
NCT00672386
Lead Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Brief Summary

The purpose of this study is to investigate the effectiveness and safety of 12 weeks of treatment with R256918 in patients with Type 2 Diabetes Mellitus who are taking metformin. The primary measure of effectiveness is the change in concentration of glycated hemoglobin (HbA1c) during treatment. Glycated hemoglobin is a substance in red blood cells that is formed when blood sugar (glucose) attaches to hemoglobin and is a measure of diabetic status. Additional measures include fasting glucose, and lipid levels, and body weight. Safety assessments performed during the trial include laboratory tests, vital sign measurements, and adverse event reporting.

Detailed Description

This is a randomized (assigned study drug by chance), double-blind (both the patient and investigator do not know whether patient is assigned to receive study drug or placebo), placebo-controlled study involving patients with Type 2 Diabetes Mellitus who are taking metformin. Patients are randomized to one of 4 treatment groups and receive study drug (R256918: 5 mg, 10 mg, or 15 mg twice daily) or placebo for a period of 12 weeks. The study consists of a screening period, a baseline visit, the treatment period of 12 weeks, and a follow-up visit. During the treatment period, patients visit the center every two weeks. On each visit, patients come to the clinic after 8 hours fasting. Effectiveness assessments from a blood sample include levels of fasting hemoglobin type A1c (HbA1c), glucose, cholesterol, triglycerides, insulin, C-peptide, and gastrointestinal hormones. Patients monitor their fasting blood glucose and record it in a diary. Insulin sensitivity and beta cell (insulin-producing cells in the pancreas) function are evaluated. Waist and hip circumference are measured. Safety evaluations, including incidence of adverse events, clinical laboratory results, vital signs, and electrocardiograms, are performed during the study. Patients complete a questionnaire related to treatment satisfaction of study medication. Patients receive dietary counseling and will be instructed to remain on a calorically appropriate diet with a maximum of 30 percent (%) of calories derived from fat (in accordance with local practice guidelines for the treatment of type 2 diabetes mellitus), during the entire study. Patients continue taking metformin in the same dose and according to the same dosing regimen as before the study. The overall duration of the study for each patient is approximately 18 weeks. The study will evaluate the effect of R25691 on glucose-dependent insulin secretion, weight loss and changes in insulin sensitivity and tolerability in type 2 diabetic patients.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
352
Inclusion Criteria
  • History of Type 2 Diabetes Mellitus and treated with a stable dose of metformin for at least 2 months
  • Women must be postmenopausal or surgically incapable of childbearing or if sexually active, be practicing an effective method of birth control
  • BMI between 25 and 45 kg/m2
  • HbA1c between 7% and 10%, inclusive
  • Fasting plasma glucose not exceeding 240mg/dL (13.3mmol/L)
Exclusion Criteria
  • Diabetes other than type 2 diabetes mellitus
  • Treatment with oral anti-diabetic agents (other than metformin) or insulin during the 12 weeks before baseline visit
  • History of intolerance or hypersensitivity to sulfonylurea or sitagliptin
  • History of clinically significant gastrointestinal, hepatic or cardiovascular disease
  • Active proliferative diabetic retinopathy
  • History of diabetic gastroparesis
  • concurrent use of systemic corticosteroid

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
004PlaceboPlacebo twice daily for 12 weeks
003JNJ16269110JNJ16269110 15 mg twice daily for 12 weeks
002JNJ16269110JNJ16269110 10 mg twice daily for 12 weeks
002Dietary CounselingJNJ16269110 10 mg twice daily for 12 weeks
001Dietary CounselingJNJ16269110 5 mg twice daily for 12 weeks
001JNJ16269110JNJ16269110 5 mg twice daily for 12 weeks
003Dietary CounselingJNJ16269110 15 mg twice daily for 12 weeks
004Dietary CounselingPlacebo twice daily for 12 weeks
001MetforminJNJ16269110 5 mg twice daily for 12 weeks
002MetforminJNJ16269110 10 mg twice daily for 12 weeks
004MetforminPlacebo twice daily for 12 weeks
003MetforminJNJ16269110 15 mg twice daily for 12 weeks
Primary Outcome Measures
NameTimeMethod
Mean change in HbA1c from baseline to week 12baseline, week 4, 6, 8, 10 and 12
Secondary Outcome Measures
NameTimeMethod
Changes in body weightevery 2 weeks
Changes in fasting plasma glucoseevery 2 weeks
Changes in insulin sensitivity and beta cell function (homeostatic model assessment 2 - HOMA-2 and MMTT); Changes in GLP-1 (glucagon-like peptide 1) and PYY (peptide tyrosine tyrozine) levels in the MMTT; Changes in insulin and glucagonbaseline and Week 12
Changes in plasma lipidsbaseline, week 6 and 12
Changes in systolic and diastolic blood pressureevery 2 weeks
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