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GSK1521498 · 4 trials · 2 indications
To test that the OPRM1 A118G polymorphism modulates the effects of GSK1521498 10 mg on brain reward function and processing
Number of subjects with any adverse events during the treatment periods
Systolic and diastolic BP will be measured
12-lead electrocardiograph (ECG) will be measured
Hematology/Chemistry assessments to be done at screening (fasted) and day 5 for each treatment session (un-fasted).
Mood anxiety will be assessed by The Beck Anxiety Inventory (BAI), The Beck Depression Inventory (BDI-II).
Suicidality will be assessed by C-SSRS.
Mood anxiety and suicidality will be assessed by VAS.
CANTAB attention tasks comprising of Simple Reaction Time (SRT), Choice Reaction Time (CRT) and Rapid Visual Information Processing (RVP) will be done to measure the power of attention
AUC and Cmax of GSK1521498 and alcohol
| Arm | Type | Description |
|---|---|---|
| 2 mg GSK1521498 | EXPERIMENTAL | Approximately 20 subjects will be randomised to receive 2 mg GSK1521498. The drug is being developed for the treatment of obesity due to excessive consumption of high calorie foods |
| 5 mg GSK1521498 | EXPERIMENTAL | Approximately 20 subjects will be randomised to receive 5 mg GSK1521498. The drug is being developed for the treatment of obesity due to excessive consumption of high calorie foods |
| Placebo | PLACEBO_COMPARATOR | Approximately 20 subjects will be randomised to receive matching placebo. |
| Treatment A | PLACEBO_COMPARATOR | Subject will receive oral dose of matching placebo once daily for 5 days in one of the 3 treatment periods. |
| Treatment B | EXPERIMENTAL | Subject will receive 25 mg orally once daily for the first two days and 50 mg once daily for 3 days in one of the 3 treatment periods. |
| Treatment C | EXPERIMENTAL | Subject will receive 10 mg orally once daily for 5 days in one of the 3 treatment periods. |
| GSK1521498 & alcohol | EXPERIMENTAL | GSK1521498 20 mg and alcohol (0.5g/kg ethanol mixed with orange juice) |
| GSK1521498 & orange juice | EXPERIMENTAL | GSK1521498 20 mg and orange juice approximately matching alcoholic beverage for volume and colour |
| Placebo & alcohol | EXPERIMENTAL | Placebo and alcohol (0.5g/kg ethanol mixed with orange juice) |
| Placebo & orange juice | PLACEBO_COMPARATOR | Placebo and orange juice approximately matching alcoholic beverage for volume and colour |
| Part A | PLACEBO_COMPARATOR | Part A: This part of the study will start with a very low dose of study drug, which will then be gradually increased in subsequent doses. This is known as dose-rising and is the way to assess safety and tolerability (i.e. possible presence of any side effects that make taking the drug unpleasant) of increasing doses of the study drug. Effects will be compared to those seen when a placebo is taken. Up to 4 groups of 6-9 healthy male or female volunteers will be enrolled. |
| Part B | ACTIVE_COMPARATOR | Part B: A dose selected from Part A that was well tolerated will be used to check if there is a difference in the pharmacokinetics (blood levels) of the study drug when taken without food in liquid form, or as a capsule, or as a capsule together with a high fat meal to assess the effect of food. One group of 12 healthy male or female volunteers will be enrolled. |
| Part C | PLACEBO_COMPARATOR | Part C: A well tolerated dose selected from Parts A \& B will be used to test whether the drug has an effect on individual preferences for sugary and high fat food, when compared to placebo. Up to 32 healthy overweight male volunteers will be enrolled. |
| Name | Type | Description |
|---|---|---|
| GSK1521498 | DRUG | GSK1521498 2mg or 5mg will be given for up to 35 days and subjects will be assessed weekly |
| Placebo | DRUG | Placebo will be given for up to 35 days and subjects will be assessed weekly |
| Naltrexone (NTX) | DRUG | Swedish orange gelatin capsule containing 25mg of NTX or 50mg of NTX |
| GSK1521498 or placebo | DRUG | GSK1521498 is a mu-opioid receptor inverse agonist |
Inclusion Criteria: * Obese but essentially healthy male or female between 18 and 60 years of age inclusive. * Body Mass Index greater than or equal to 30 kg/m2. * Binge Eating Scale (BES) score that is greater than or equal to 19 at screening assessment. * A female subject of child-bearing potenti...
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GSK1521498 is an investigational small molecule developed by GSK plc for alcoholism and obesity. It is an antagonist of OPRM1, the mu opioid receptor. The compound has completed Phase 1 and Phase 2 clinical trials and has not been approved for any indication.
GSK1521498 has been studied for alcoholism and obesity. Clinical trials enrolled healthy social drinkers and obese subjects with over-eating behaviours. It remains investigational and is not approved for the treatment of either condition.
GSK1521498 targets OPRM1, the mu opioid receptor. It acts as an antagonist at this receptor. One Phase 1 trial examined how the A118G polymorphism in the OPRM1 gene influences the effects of GSK1521498 and naltrexone on physiological and behavioural markers of brain function.
GSK1521498 is developed by GSK plc, which trades under the ticker GSK. The company sponsored the clinical trials of the compound in alcoholism and obesity.
GSK1521498 is in Phase 1 development overall, with completed Phase 1 trials in healthy volunteers and a completed Phase 2 trial in obese subjects with over-eating behaviours. It is investigational and has not been approved by the FDA or any regulator.
GSK1521498 has completed four trials: NCT01738867 and NCT01366573 in alcoholism, NCT01195792 in obesity, and NCT00857883, a first-time-in-human study in healthy subjects. All are completed, with no active trials. Total enrollment across the studies was 116 participants.