Effects of Repeat Dosing of GSK1521498
|Obesity||Drug: Zolpidem or placebo - Hypnotic drug given for sleep disorders Drug: GSK1521498 or placebo||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
|Official Title:||A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of 10 Days of Repeat Dosing of GSK1521498 in Overweight or Obese But Otherwise Healthy Subjects.|
- Safety and tolerability: adverse events, blood pressure, heart rate, ECG, clinical chemistry, heamatology, urinalysis, change in reaction times, change in mood scales [ Time Frame: During 10 days of repeat dosing ]
- Obtain benchmarking data on the cognitive and mood changes induced by a single dose of up to 10mg zolpidem [ Time Frame: Single occasion ]
- Assess accumulation, dose proportionality and pharmacokinetics of GSK1521498: AUC (0-24), Cmax, tmax, tlag (Dose 1 only), t1/2 (Dose 10 only), trough plasma concentrations on Day 5, 7, 8, 9 and 10 [ Time Frame: On Day 1 and/or following 10 days of repeat dosing and trough samples on Day 5, 7, 8, 9 and 10 ]
- PK/PD relationships: cognitive and mood changes, pressure pain threshold and tolerance, heat pain threshold [ Time Frame: During 10 days of reapeat dosing ]
- Assess effects on body weight, fat mass, eating behaviour and personality traits: Bodyweight and BMI, Fat mass (ECHO-MRI), food ingested and energy intake, eating behaviour and persoality scales: Y-BOC-BE, BE, TFEQ and BIS [ Time Frame: Screening, or Day -1 and Day 10 ]
|Actual Study Start Date:||September 22, 2009|
|Study Completion Date:||March 9, 2010|
|Primary Completion Date:||March 9, 2010 (Final data collection date for primary outcome measure)|
Active Comparator: Part A: Zolpidem or placebo
This part is designed to examine the acute effects of up to 10mg of a known hypnotic sedative drug (Zolpidem) on cognitive and mood changes sensitve to sedation and tiredess.
Drug: Zolpidem or placebo - Hypnotic drug given for sleep disorders
The information gathered from Part A will be used as a benchmark against which any effects of GSK1521498 can be assessed in Part B.
Experimental: Part B: GSK1521498 or placebo
At least 15 hours after Part A is completed subjects will enter Part B of the study.
Drug: GSK1521498 or placebo
The first group will start at a low dose (10 mg GSK1521498 or placebo) for 10 days. The study team will then assess the data gathered from the first cohort and will select the dose that the next cohort will receive for 10 days. There will be up to 4 cohorts.
This study is to test a new drug which may be used for treating eating behaviour and patterns that some overweight and obese patients find difficult to control. The drug works by inhibiting the effects of messenger molecules called opioids, e.g. endorphins. These opioids are naturally produced within the human body and control hunger, thirst, and the pleasurable feelings we relate to eating food. The drug attaches to opioid binding sites in the brain, known as mu-opioid receptors; this blocks the natural effect of opioids which may reduce the craving to eat fatty or sugary foods. Single doses of the drug have been given to humans and showed it was safe. Now the drug will be given every day for 10 days to check that the drug is safe and tolerated when given repeatedly. The study is in two parts:
Part A: people will receive a sleeping tablet to make them sleepy (or a dummy drug) and will complete some questionnaires and simple tests including computer exercises to test the effect of this tablet on mood and cognition. This information will be used to help judge what is happening in Part B.
Part B: requires staying in the unit for 10 days to receive a tablet every day and complete questionnaires and other tests to check for any mood and cognitive changes. Various other assessments will include effects on eating behaviour, pain measures and changes in body composition (content of fat, muscle and water).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00976105
|GSK Investigational Site|
|Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|