Clinical trial NCT00672386: A Study of the Safety and Effectiveness of a R256918 in Patients With Type 2 Diabetes
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Nutritional and Metabolic Diseases
Keywords: Diabetes
Type 2 Diabetes
Adult-Onset Diabetes Mellitus
Metabolic Syndrome
HbA1c
Body Weight
Metformin
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2008-05-06
Enrollment: 352
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean change in HbA1c from baseline to week 12
timeFrame: baseline, week 4, 6, 8, 10 and 12
Secondary outcomes:
measure: Changes in fasting plasma glucose
timeFrame: every 2 weeks
measure: Changes in body weight
timeFrame: every 2 weeks
measure: Changes in plasma lipids
timeFrame: baseline, week 6 and 12
measure: Changes in systolic and diastolic blood pressure
timeFrame: every 2 weeks
measure: 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
timeFrame: baseline and Week 12
Other outcomes:
Locations:
city: Edegem
country: Belgium
city: Hellerup N/A
country: Denmark
city: Vipperroed
country: Denmark
city: Helsinki
country: Finland
city: Hyvinkaa
country: Finland
city: Kuopio
country: Finland
city: Oulu
country: Finland
city: Berlin Buch
country: Germany
city: Dresden
country: Germany
city: Düsseldorf
country: Germany
city: Hamburg
country: Germany
city: Mainz
country: Germany
city: Munchen
country: Germany
city: Ulm
country: Germany
city: Bangalore
country: India
city: Chennai
country: India
city: Hyderabad
country: India
city: Mumbai
country: India
city: Nagpur
country: India
city: Pune
country: India
city: Breda
country: Netherlands
city: Eindhoven
country: Netherlands
city: Leiden
country: Netherlands
city: Nijmegen
country: Netherlands
city: Rotterdam
country: Netherlands
city: Velp Gld
country: Netherlands
city: Zoetermeer
country: Netherlands
city: Oslo
country: Norway
city: Paradis N/A
country: Norway
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Elblag
country: Poland
city: Kutno 001
country: Poland
city: Lodz
country: Poland
city: Olsztyn
country: Poland
city: Pruszkow
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Zielona Gora
country: Poland
city: Moscow
country: Russian Federation
city: Saratov
country: Russian Federation
city: St Petersburg N/A
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Göteborg
country: Sweden
city: Härnösand
country: Sweden
city: Linköping
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Ängelholm N/A
country: Sweden
city: Örebro
country: Sweden
city: Bangor
country: United Kingdom
city: Belfast
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Clydebank
country: United Kingdom
city: Dundee
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Randalstown
country: United Kingdom
city: Reading
country: United Kingdom
city: Salford
country: United Kingdom
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References: