A Study of the Safety of R256918 in Obese Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Metabolic Diseases; Obesity; Nutrition Disorders; Overweight; Nutritional and Metabolic Diseases
• Intervention / Treatment: Drug: R256918; Drug: R256918; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
• Netherlands
  • Zuidlaren, Netherlands
• Sweden
  • Göteborg, Sweden

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 001; R256918 10 mg capsule twice daily	Drug: R256918; 10 mg capsule twice daily; Drug: R256918; 15 mg capsule twice daily
Experimental: 002; R256918 15 mg capsule twice daily	Drug: R256918; 10 mg capsule twice daily; Drug: R256918; 15 mg capsule twice daily
Placebo Comparator: 003; placebo placebo capsule twice daily	Drug: placebo; placebo capsule twice daily

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

Helpful Links

• A Study of the Safety of R256918 in Obese Patients

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: December 30, 2009
• First Submitted That Met QC Criteria: December 30, 2009
• First Posted (Estimate): January 1, 2010

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 15, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Obesity; Overweight; Body Weight; Nutritional and Metabolic Diseases; Body Size
• Additional Relevant MeSH Terms: Body Weight; Overweight; Nutrition Disorders; Metabolic Diseases
• Other Study ID Numbers: CR013735