GSK1521498 is a novel opioid receptor inverse agonist that is being developed for the treatment of obesity. MedDRA version: 12.1 Level: LLT Classification code 10029883 Term: Obesity
Conditions
Interventions
Product Name: GSK1521498
Product Code: GSK1521498
Pharmaceutical Form: Capsule*
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use
Product Name: GSK1521498
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Obese but essentially healthy male or female between 18 and 60 years of age inclusive, at the time of signing the informed consent form. 2. Body Mass Index greater than or equal to 30 kg/m2. There is no upper limit on BMI subject to satisfaction of all other exclusion criteria. 3. Binge Eating Scale (BES) score that is greater than or equal to 19 at screening assessment. 4. A female subject of child-bearing potential is eligible to participate if she agrees to use an adequate contraception method for an appropriate period of time (as defined in the protocol) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until at least 14 days after receiving the last dose of study medication. 5. Male subjects must agree to use an adequate contraception method from the time of the first dose of study medication until at least 5 days after receiving the last dose of study medication. 6. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the information sheet or informed consent form. A good understanding of English is required due to the high number of questionnaires and assessments that subjects are required to undergo. 7. AST and ALT 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subject has a history of clinically significant medically diagnosed eating disorders (diagnosed and/or treated) as assessed by DSM-IV/V criteria using the MINI. 2. Self-administered Beck Depression Inventory II scale total score greater than 13 or suicide question score greater than zero at screening. 3. Subject who have a current history (in the last 6 months) of any Axis 1 psychiatric disorder as assessed by DSM-IV/V criteria using the MINI. 4. Subject who, in the investigator/designee's judgement, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behaviour and/or any evidence of suicidal ideation on any questionnaires e.g. type 4 or 5 on the C-SSRS in the last 6 months. 5. Subject has a history of substance abuse or dependence in the 6 months prior to screening, as determined by the Investigator/designee or MINI. 6. Abuse of alcohol, defined for males, as an average weekly intake of greater than 21 units (or an average daily intake of greater than 3 units), or defined for females, as an average weekly intake of greater than 14 units (or an average daily intake of greater than 2 units). One unit is equivalent to a half-pint (220mL) of beer or 1 (25mL) measure of spirits or 1 glass (125mL) of wine. 7. Positive urine screen for amphetamines, barbiturates, cocaine, opiates, cannabinoids or benzodiazepines at screening. 8. Smoking history that includes regular use of tobacco or nicotine-containing products within 3 months prior to screening 9. Subjects who do not currently show stable bodyweight, as judged by the PI/designee (e.g. >5% change within the last 3 months) 10. Pregnant or lactating females 11. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 12. Any contraindications or logistical complications anticipated in relation to MRI scanning or other endpoint assessments, in the judgment of the Principal Investigator, including: presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies as assessed by a standard pre-MRI questionnaire, claustrophobia, inability to lie still on back, waist circumference of more than 170 cm or body weight exceeding maximum capacity of MRI scanners (180 kg). In some cases, at the discretion of the investigator, subjects with a waist circumference over 170 cm may be included in the study and will undergo all procedures except MRI scans.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the trial is to test the hypothesis that GSK1521498 will cause clinically and statistically significant (at least -2.1kg) placebo-controlled change from baseline body weight after 28 days repeat dosing with 2 mg and 5 mg in obese subjects with moderate to-high binge eating behaviours.;Secondary Objective: The second objectives of the trial are: • To explore the hypothesis that the effects of GSK1521498 on body weight will be associated with significant effects on fat mass, eating behaviour, reward-related brain function, hedonic and motivational processing, peripheral blood and urinary biomarkers. • To explore the hypothesis that therapeutic effects of GSK1521498 on body weight and other efficacy endpoints in obese patients will be correlated with over-eating behaviour at baseline. • To evaluate potential adverse effects of GSK1521498 as measured by a) standard clinical safety measures, b) detailed neuropsychological testing of cognition, and c) assessment of neuropsychiatric symptoms. • To assess the repeat dosing pharmacokinetic parameters of GSK1521498 and to explore the PK/PD relationships between GSK1521498 exposures and its effects on the primary and secondary endpoints, including estimation of possible dose-response relationships. ;Primary end point(s): All endpoints will be measured in terms of placebo-controlled change from baseline after 28 days of treatment with GSK1521498 at doses of 2 mg or 5 mg. Some endpoints will also be measured after 14 days of treatment to assess change in treatment effects over the course of repeated dosing. The primary endpoint is change in body weight at Day 28 compared to baseline. | — |
Countries
United Kingdom
Outcome results
None listed