This is a first-time-in-human study. The overall purpose of the study is to assess whether the drug is safe and well tolerated after single, increasing doses. The blood levels of the drug after different doses will be measured and the effect of the drug on pleasurable eating behaviour will be assessed.
The human body naturally produces substances known as opioids and the pleasurable (or hedonic) response to eating highly sugary or fatty foods is increased by opioids. The drug to be tested in this study attaches to specific binding sites in the brain, known as mu-opioid receptors. This may stop the natural effect of opioids and therefore reduce the pleasurable response to food. We predict that this in turn may help patients with obesity to lose weight more effectively. The study is divided into three parts: Part A: This part of the study will start with a very low dose of study drug, which will then be gradually increased in subesquent doses. This is known as dose-rising and is the way to assess safety and tolerability (any side effects that make taking the drug unpleasant). Effects will be compared to those seen when a placebo (a "dummy" drug) is taken. Up to 4 groups of 6-9 healthy male or female volunteers will be enrolled in this part of the study. Part B: A dose selected from Part A that was well tolerated will be used to check if there is a difference in the blood levels of the study drug when taken without food in liquid form, without food as a capsule, or with a high fat meal as a capsule. One group of 12 healthy male or female volunteers will be enrolled in this part of the study. Part C: A well tolerated dose selected from Parts A \& B will be used to test whether the drug has an effect on preferences for sugary and high fat food, when compared to placebo. Up to 32 healthy overweight male volunteers will be enrolled in this part of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
56
GSK1521498 is a mu-opioid receptor inverse agonist
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom
Safety: adverse events, changes in clinical chemistry, haematology, urine parameters, blood pressure, heart rate, ECG, Bond & Lader visual Analog Scale, Profile of Mood States
Time frame: 19 weeks
Tolerability: adverse events, changes in clinical chemistry, haematology, urine parameters, blood pressure, heart rate, ECG, Bond & Lader visual Analog Scale, Profile of Mood States
Time frame: 19 weeks
Pharmacokinetic parameters
Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post dose administrations
Bioavailability of liquid form of drug and capsule and effect of food on the capsule
Time frame: Approx 4 weeks
Pharmacodynamics - response to sweet and high fat foods before and after drug administration
Time frame: Approx 10 weeks
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