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.
Overview
- Phase
- Phase 1
- Intervention
- Zolpidem or placebo - Hypnotic drug given for sleep disorders
- Conditions
- Obesity
- Sponsor
- GlaxoSmithKline
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- Safety and tolerability: adverse events, blood pressure, heart rate, ECG, clinical chemistry, heamatology, urinalysis, change in reaction times, change in mood scales
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The overall purpose of this study is to see whether the drug is safe and well tolerated when given to overweight or obese but otherwise healthy volunteers for 10 days. Up to 4 groups of people will be given the drug at variable strengths. The blood levels of the drug will be measured and the effects on mood and cognition (the mental processes involved in awareness, learning and judgement) will be assesed.
Detailed Description
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy as determined by a responsible and experienced physician
- •Non smoking male or female between 18 and 60 years of age inclusive
- •A female subject of child-bearing potential must use a contraception method listed in the protocol prior to the start of dosing until at least 14 days after receiving the last dose of study medication.
- •Male subjects must agree to use one of the contraception methods listed in the protocol from the first dose of study medication until at least 84 days after receiving the last dose of study medication.
- •BMI within the range 25 - 35 kg/m2 (inclusive).
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- •QTcB or QTcF \< 450 msec.
- •Suitable for repeat cannulation.
Exclusion Criteria
- •Has clinically significant rhythm abnormalities identified during 24-hour screening Holter assessment.
- •Systolic blood pressure greater than 150 mmHg and/or diastolic BP greater than 90 mmHg.
- •Diabetes mellitus or physician-diagnosed dyslipidaemia requiring treatment
- •Self-administered Beck Depression Inventory II scale total score greater than 13 or suicide question score greater than zero at screening.
- •Positive pre-study drug/alcohol screen
- •Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- •Positive test for HIV antibody.
- •Pregnant or lactating females
- •Smoking history that includes regular use of tobacco or nicotine-containing products within 6 months prior to screening.
- •A history of any thyroid dysfunction or an abnormal thyroid function test
Arms & Interventions
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.
Intervention: Zolpidem or placebo - Hypnotic drug given for sleep disorders
Part B: GSK1521498 or placebo
At least 15 hours after Part A is completed subjects will enter Part B of the study.
Intervention: GSK1521498 or placebo
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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(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(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(Screening, or Day -1 and Day 10)