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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A 12-Week, Double-Blind, Randomized, Placebo-Controlled Study in Type 2 Diabetes Mellitus Subjects to Evaluate the Efficacy, Safety and Tolerability of MTP Inhibitor JNJ-16269110 (R256918)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00672386
• Other study ID #: CR013051
• Secondary ID: CR013051
• Status: Completed
• Phase: Phase 2
• First received: May 2, 2008
• Last updated: July 10, 2014
• Start date: December 2007
• Est. completion date: September 2008

Study information

• Verified date: July 2014
• Source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardDenmark: Danish Medicines AgencyGreat Britain: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 352
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Endocrine System Diseases
• Metabolic Diseases
• Nutritional and Metabolic Diseases

Intervention

Drug:
• JNJ16269110
5 mg twice daily for 12 weeks
• JNJ16269110
10 mg twice daily for 12 weeks
• JNJ16269110
15 mg twice daily for 12 weeks
• Placebo
twice daily for 12 weeks
• Metformin
Participants will continue taking metformin at the same dose and according to the same dosing regimen as before the study.

Other:
• Dietary Counseling
Participants will receive dietary counseling at Screening, Week 4, 8, 12, and will be instructed to remain on a calorically appropriate diet with a maximum of 30% of calories derived from fat (in accordance with local practice guidelines for the treatment of type 2 diabetes mellitus) during the entire study.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Countries where clinical trial is conducted

Belgium,  Denmark,  Finland,  Germany,  India,  Netherlands,  Norway,  Poland,  Russian Federation,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in HbA1c from baseline to week 12		baseline, week 4, 6, 8, 10 and 12	No
Secondary	Changes in fasting plasma glucose		every 2 weeks	No
Secondary	Changes in body weight		every 2 weeks	No
Secondary	Changes in plasma lipids		baseline, week 6 and 12	No
Secondary	Changes in systolic and diastolic blood pressure		every 2 weeks	No
Secondary	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 glucagon		baseline and Week 12	No