E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
GSK1521498 is a novel opioid receptor inverse agonist that is being developed for the treatment of obesity. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029883 |
E.1.2 | Term | Obesity |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
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E.3 | Principal 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 < 2xULN; alkaline phosphatase and bilirubin <= 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 8. Must be right handed (a requirement to ensure consistency of fMRI signals from the brain) |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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A completed subject is one who has completed all 35 days of dosing and both follow-up visits. The end of the study is defined as the last subject’s last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 35 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 35 |