Investigation Of Weight Loss And Body Composition Changes After Dosing With Either Placebo Or One Of Two Active Drugs

Study Overview
=================
Brief Summary
-----------------
The drugs GSK189075 and GW869682 result in increased caloric losses. This study is investigating how if taken over 8 weeks that affects weight loss, food intake and the composition of the body. The body composition (fat,water, lean mass) is determined using a new investigational MR technology.

Official Title
-----------------
An Exploratory Study to Evaluate Weight Loss, Body Composition Changes, Food Intake and Urine Glucose Excretion in Healthy Obese Subjects Over 8 Weeks of Dosing With GSK189075, GW869682 Versus Placebo

Conditions
-----------------
Diabetes Mellitus, Type 2, Obesity

Intervention / Treatment
-----------------
* Drug: GW869682
* Drug: GSK189075
* Drug: GSK189075-Placebo
* Drug: GW869682-Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: BMI of 30 - 40kg/m Females may be included if they are surgically sterile or post-menopausal Exclusion criteria: Change in body weight >4% in the last 3 months History of eating disorders had bariatric surgical intervention for obesity have type I or II diabetes Thyroid disorder not under control Renal or hepatobiliary disease Excessive alcohol consumption Use of drugs of abuse donated of blood in the last 3 months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GW869682 1000 mg thrice daily (TID)<br>Subjects will be randomized to receive GW869682 1000 mg TID | Drug: GW869682<br>* GW869682 tablet with a dose strength of 250 mg will be available for subjects<br>Drug: GSK189075<br>* GSK189075 tablet with a dose strength of 250 mg will be available for subjects<br>* Other names: GW869682;Drug: GSK189075-Placebo<br>* Placebo tablets to match GSK189075 250 mg will be available for subjects<br>Drug: GW869682-Placebo<br>* Placebo tablets to match GW869682 250 mg will be available for subjects<br>|
| Experimental: GSK189075 250 mg TID<br>Subjects will be randomized to receive GSK189075 250 mg TID | Drug: GW869682<br>* GW869682 tablet with a dose strength of 250 mg will be available for subjects<br>Drug: GSK189075<br>* GSK189075 tablet with a dose strength of 250 mg will be available for subjects<br>* Other names: GW869682;Drug: GSK189075-Placebo<br>* Placebo tablets to match GSK189075 250 mg will be available for subjects<br>Drug: GW869682-Placebo<br>* Placebo tablets to match GW869682 250 mg will be available for subjects<br>|
| Placebo Comparator: GW869682-Placebo TID<br>Subjects will be randomized to receive Placebo matching GW869682 for TID | Drug: GW869682<br>* GW869682 tablet with a dose strength of 250 mg will be available for subjects<br>Drug: GSK189075<br>* GSK189075 tablet with a dose strength of 250 mg will be available for subjects<br>* Other names: GW869682;Drug: GSK189075-Placebo<br>* Placebo tablets to match GSK189075 250 mg will be available for subjects<br>Drug: GW869682-Placebo<br>* Placebo tablets to match GW869682 250 mg will be available for subjects<br>|
| Placebo Comparator: GSK189075-Placebo TID<br>Subjects will be randomized to receive Placebo matching GSK189075 for TID | Drug: GW869682<br>* GW869682 tablet with a dose strength of 250 mg will be available for subjects<br>Drug: GSK189075<br>* GSK189075 tablet with a dose strength of 250 mg will be available for subjects<br>* Other names: GW869682;Drug: GSK189075-Placebo<br>* Placebo tablets to match GSK189075 250 mg will be available for subjects<br>Drug: GW869682-Placebo<br>* Placebo tablets to match GW869682 250 mg will be available for subjects<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body fat and fat-free mass as determined by a new investigational MR technique compared to 4C Model methodologies. |  | Measurements at week 8 will be compared to measurements from Day -1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (caloric losses body weight, body composition, weight and hip circumference.) |  | throughout study (Days 1-56) | 
| Leptin levels in serum |  | at several points during study | 
| Drug levels in blood over time (Day 42 PK parameters are AUC, Cmax, tmax) |  | Day 42 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
body composition, obesity, 4C model, hunger, weight loss