A Study of the Safety of R256918 in Obese Patients

Study Overview
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Brief Summary
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This study investigates the safety of 12 weeks of treatment with R256918, in obese patients (JNJ-16269110 and R256918 are different names for the same molecule). The primary objective of the study is to investigate mean changes in Hepatic Triglyceride Content (HTGC), which is the fat content of the liver, from baseline to week 6 and 12 by 1H-Magnetic Resonance Spectroscopy (MRS), a specialized non invasive radiology test. Additional measures include body mass index (BMI), fasting glucose,lipid levels, and blood pressure. Safety assessments performed during the trial include laboratory tests, vital sign measurements, and adverse event reporting.

Detailed Description
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This is a randomized (study drug assigned by chance), double-blind (neither physician nor patient knows the name of the assigned drug), placebo-controlled , parallel-group study with 3 treatment arms, each consisting of 27 obese patients. The study will include 3 phases - pretreatment, double-blind and posttreatment . During the pretreatment phase patients undergo general screening assessments and if eligible, Magnetic Resonance Spectroscopy (MRS) screening will be performed. During the double-blind treatment phase patients will receive dietary counseling, study medication, have urine and blood laboratory tests, a follow up MRS examination and have regular clinic visits for symptoms assessment. The double blind treatment phase ends with an end-of-treatment or early withdrawal visit. A patient withdrawing from the study prior to the end of the 12 week treatment phase will attend an early withdrawal visit, which is the same as the end-of-treatment visit. This visit will include laboratory tests and a follow up MRS examination. Post-treatment: A follow-up evaluation will occur 14 days after the end of treatment. Study visits are scheduled to occur nearly every 14 days following the baseline visit in week 1. The total study duration is approximately 15 weeks. The study will include the following evaluations of safety and tolerability: mean percent change in liver fat content at week 6 and week 12 or at the end of the patients participation in the study, in case of early withdrawal. Safety evaluations for the study will include the monitoring of adverse events, clinical laboratory tests including pregnancy testing, electrocardiograms (ECGs), vital sign measurements (pulse and blood pressure), physical examination, and patient reported assessment of GI symptoms. Special clinical laboratory safety tests will assess blood clotting or coagulation status, essential fatty acid status, lipid-soluble vitamin status: vitamin A, vitamin D, vitamin E, vitamin K, vitamin A/total cholesterol ratio, vitamin E/total cholesterol ratio and liver function tests. 10 mg capsules, 15 mg capsules, or matching placebo capsules taken orally.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-Center Study to Evaluate the Effect of JNJ-16269110 on Hepatic Triglyceride Content in Obese Subjects

Conditions
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Nutrition Disorders, Obesity, Nutritional and Metabolic Diseases, Metabolic Diseases, Overweight

Intervention / Treatment
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* Drug: R256918
* Drug: placebo
* Drug: R256918


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver fat content (HTGC) between 3% and 15% Obese defined as BMI between 30 and 50 kg/square meter Fasting plasma glucose < 7.0 mmol/liter Exclusion Criteria: History of Obesity with a known cause (eg. Cushings disease) Diabetes Mellitus Weight reducing diet or receiving drugs to treat obesity within 3 months prior to screening Significant change in smoking habits within 3 months before enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>R256918 10 mg capsule twice daily | Drug: R256918<br>* 10 mg capsule twice daily<br>|
| Experimental: 002<br>R256918 15 mg capsule twice daily | Drug: R256918<br>* 15 mg capsule twice daily<br>|
| Placebo Comparator: 003<br>placebo placebo capsule twice daily | Drug: placebo<br>* placebo capsule twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic Triglyceride Content (HTGC) as measured by 1H-Magnetic Resonance Spectroscopy (MRS). |  | Baseline, 6 weeks, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body weight |  | Baseline, weeks 1, 2, 4, 6, 8,10,12,14 | 
| Change in alanine aminotransferase and aspartate aminotransferase |  | Baseline, weeks 4, 6, 8,12,14 | 
| Changes in fasting glucose and insulin |  | Baseline, weeks 6, 12 | 
| Changes in systolic and diastolic blood pressure |  | Baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14 | 
| Changes in total-, HDL- and LDL-cholesterol and triglycerides |  | Baseline, weeks 6,12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Overweight, Body Weight, Body Size, Nutritional and Metabolic Diseases