A 35 Day Study to Investigate the Effects of GSK1521498 on Bodyweight in Obese Subjects With Over-Eating Behaviours.

NCT01195792 | Completed Phase 2

• 1 other identifier: 111850
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine whether GSK1521498 will cause weight loss in obese but otherwise healthy subjects with over-eating behaviours.

Conditions

Obesity

Keywords

Opioid receptors; Body weight; Over-eating behaviour; Obesity; Fat mass

Outcome Measures

Primary Outcomes (1)

• Clinically and statistically significant weight loss

  35 days

Secondary Outcomes (4)

• To see if effects on bodyweight are associated with effects on fat mass, eating behaviour brain function and blood and urine markers

  35 days

• To see if effects on bodyweight correlate with over-eating behaviour at baseline

  35 days

• Safety: adverse events,blood pressure, heart rate, ECG, clinical chemistry, hematology, urinalysis, change in cognition (eg reaction times), change in mood scales, change in neuropsychiatric symptoms

  35 days

• Pharmacokinetic/Pharmacodynamic (PK/PD) relationships: effects on primary and secondary outcomes, including estimation of possible dose-response relationships

  35 days

Study Arms (3)

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

Drug: GSK1521498

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

Drug: GSK1521498

Placebo

PLACEBO COMPARATOR

Approximately 20 subjects will be randomised to receive matching placebo.

Drug: Placebo

Interventions

GSK1521498 DRUG

GSK1521498 2mg or 5mg will be given for up to 35 days and subjects will be assessed weekly

2 mg GSK1521498; 5 mg GSK1521498

Placebo DRUG

Placebo will be given for up to 35 days and subjects will be assessed weekly

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 potential must use one of the contraception methods listed in the protocol prior to the start of the study 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 time of the first dose of study medication until at least 5 days after receiving the last dose of study medication.
• 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.
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \< 2x Upper limit of Normal (ULN); alkaline phosphatase and bilirubin \<1.5x (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Must be right handed (a requirement to ensure consistency of functional magnetic resonance imaging (fMRI) signals from the brain)

You may not qualify if:

• Has a history of clinically significant medically diagnosed eating disorders (diagnosed and/or treated) as assessed by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV/V) criteria using the Mini International Neuropsychiatric Interview (MINI).
• Self-administered Beck Depression Inventory II scale total score greater than 13 or suicide question score greater than zero at screening.
• Current history (in the last 6 months) of any Axis 1 psychiatric disorder as assessed by DSM-IV/V criteria using the MINI.
• 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 Columbia Suicide Severity Rating Scale (C-SSRS) in the last 6 months.
• History of substance abuse or dependence in the 6 months prior to screening, as determined by the Investigator/designee or MINI.
• History of regular high level of alcohol consumption.
• Positive pre-study drug/alcohol screen.
• Smoking history that includes regular use of tobacco or nicotine-containing products within 3 months prior to screening
• Use of prohibited medications.
• use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 14 days prior to the first dose of study medication.
• Subjects who do not currently show stable bodyweight, as judged by the PI/designee (e.g. \>5% change within the last 3 months)
• Pregnant or lactating females
• Medical history, concurrent medical condition or laboratory result which makes the subject unsuitable for the study. This includes T1 or T2 diabetes mellitus (Fasting Blood Glucose (FBG) \>7 mmol/L), untreated dyslipidaemia (fasting lipid profile with a Low Density Lipoprotein (LDL) cholesterol \> 5 mmol/L), uncontrolled hypertension
• History of bariatric surgery for obesity.
• QTcB or QTcF \> 450 msec.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

GSK Investigational Site

Birmingham, West Midlands, B15 3ES, United Kingdom

Location

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Publications (3)

• Chamberlain SR, Mogg K, Bradley BP, Koch A, Dodds CM, Tao WX, Maltby K, Sarai B, Napolitano A, Richards DB, Bullmore ET, Nathan PJ. Effects of mu opioid receptor antagonism on cognition in obese binge-eating individuals. Psychopharmacology (Berl). 2012 Dec;224(4):501-9. doi: 10.1007/s00213-012-2778-x. Epub 2012 Jul 3.

  PMID: 22752384 BACKGROUND

• Ziauddeen H, Chamberlain SR, Nathan PJ, Koch A, Maltby K, Bush M, Tao WX, Napolitano A, Skeggs AL, Brooke AC, Cheke L, Clayton NS, Sadaf Farooqi I, O'Rahilly S, Waterworth D, Song K, Hosking L, Richards DB, Fletcher PC, Bullmore ET. Effects of the mu-opioid receptor antagonist GSK1521498 on hedonic and consummatory eating behaviour: a proof of mechanism study in binge-eating obese subjects. Mol Psychiatry. 2013 Dec;18(12):1287-93. doi: 10.1038/mp.2012.154. Epub 2012 Nov 13.

  PMID: 23147384 BACKGROUND

• Cambridge VC, Ziauddeen H, Nathan PJ, Subramaniam N, Dodds C, Chamberlain SR, Koch A, Maltby K, Skeggs AL, Napolitano A, Farooqi IS, Bullmore ET, Fletcher PC. Neural and behavioral effects of a novel mu opioid receptor antagonist in binge-eating obese people. Biol Psychiatry. 2013 May 1;73(9):887-94. doi: 10.1016/j.biopsych.2012.10.022. Epub 2012 Dec 14.

  PMID: 23245760 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Obesity; Body Weight

Interventions

N-((3,5-difluoro-3'-(1H-1,2,4-triazol-3-yl)-4-biphenylyl)methyl)-2,3-dihydro-1H-inden-2-amine

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2010
• First Posted: September 6, 2010
• Study Start: September 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: December 1, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

GB (3)