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

Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)

Overall Status

Completed

CT.gov ID

NCT00672386

Collaborator

(none)

352

Enrollment

Locations

Arms

Duration (Months)

5.6

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Nutritional and Metabolic Diseases	Drug: JNJ16269110 Drug: JNJ16269110 Drug: JNJ16269110 Drug: Placebo Drug: Metformin Other: Dietary Counseling	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

352 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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)

Study Start Date :

Dec 1, 2007

Actual Primary Completion Date :

Sep 1, 2008

Actual Study Completion Date :

Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 001 JNJ16269110 5 mg twice daily for 12 weeks	Drug: JNJ16269110 5 mg twice daily for 12 weeks Drug: 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.
Experimental: 002 JNJ16269110 10 mg twice daily for 12 weeks	Drug: JNJ16269110 10 mg twice daily for 12 weeks Drug: 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.
Experimental: 003 JNJ16269110 15 mg twice daily for 12 weeks	Drug: JNJ16269110 15 mg twice daily for 12 weeks Drug: 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.
Placebo Comparator: 004 Placebo twice daily for 12 weeks	Drug: Placebo twice daily for 12 weeks Drug: 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.

Outcome Measures

Primary Outcome Measures

Mean change in HbA1c from baseline to week 12 [baseline, week 4, 6, 8, 10 and 12]

Secondary Outcome Measures

Changes in fasting plasma glucose [every 2 weeks]
Changes in body weight [every 2 weeks]
Changes in plasma lipids [baseline, week 6 and 12]
Changes in systolic and diastolic blood pressure [every 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 glucagon [baseline and Week 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	Country
1	Edegem	Belgium
2	Hellerup N/A	Denmark
3	Vipperroed	Denmark
4	Helsinki	Finland
5	Hyvinkaa	Finland
6	Kuopio	Finland
7	Oulu	Finland
8	Berlin Buch	Germany
9	Dresden	Germany
10	Düsseldorf	Germany
11	Hamburg	Germany
12	Mainz	Germany
13	Munchen	Germany
14	Ulm	Germany
15	Bangalore	India
16	Chennai	India
17	Hyderabad	India
18	Mumbai	India
19	Nagpur	India
20	Pune	India
21	Breda	Netherlands
22	Eindhoven	Netherlands
23	Leiden	Netherlands
24	Nijmegen	Netherlands
25	Rotterdam	Netherlands
26	Velp Gld	Netherlands
27	Zoetermeer	Netherlands
28	Oslo	Norway
29	Paradis N/A	Norway
30	Bialystok	Poland
31	Bydgoszcz	Poland
32	Elblag	Poland
33	Kutno 001	Poland
34	Lodz	Poland
35	Olsztyn	Poland
36	Pruszkow	Poland
37	Torun	Poland
38	Warszawa	Poland
39	Wroclaw	Poland
40	Zielona Gora	Poland
41	Moscow	Russian Federation
42	Saratov	Russian Federation
43	St Petersburg N/A	Russian Federation
44	St-Petersburg	Russian Federation
45	Göteborg	Sweden
46	Härnösand	Sweden
47	Linköping	Sweden
48	Lund	Sweden
49	Stockholm	Sweden
50	Ängelholm N/A	Sweden
51	Örebro	Sweden
52	Bangor	United Kingdom
53	Belfast	United Kingdom
54	Birmingham	United Kingdom
55	Cambridge	United Kingdom
56	Cardiff	United Kingdom
57	Clydebank	United Kingdom
58	Dundee	United Kingdom
59	Liverpool	United Kingdom
60	London	United Kingdom
61	Randalstown	United Kingdom
62	Reading	United Kingdom
63	Salford	United Kingdom

Sponsors and Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.