Last updated: 11/07/2018 04:08:19

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

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GSK study ID

111850

See study documents

Clinicaltrials.gov ID

NCT01195792

See results summary

EudraCT ID

2009-016663-11

EU CT Number

Not applicable

Trial status

Study complete

Overview

Eligibility

Locations

Study documents

Results summary

Plain language summaries

Additional information

Trial overview

Official title: A 35-Day, Multi-Centre, Randomised, Parallel-Group, Double-Blind, Placebo-Controlled Proof of Concept Study to Investigate the Effects of GSK1521498 on Body Weight and Composition, Eating Behaviour and Related Brain Function, in Obese Subjects with Over-Eating Behaviours.

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

Primary purpose:

Treatment

Trial design:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Allocation:

Randomized

Primary outcomes:

Change in body weight up to Day 28 compared with Baseline

Timeframe: Baseline (Day -1 pre-dose) and Day 14, 28

Secondary outcomes:

Change from Baseline in body mass index (BMI)

Timeframe: Baseline (Day -1 pre-dose) and Day 14, 28

Change from Baseline in hip-waist circumference ratio

Timeframe: Baseline (Day -1 pre-dose) and Day 14, 28

Change from Baseline in total fat mass, measured by Echo magnetic resonance imaging (EchoMRI)

Timeframe: Baseline (Day -1 pre-dose) and Day 14, 28

Change from Baseline in total lean mass, measured by EchoMRI

Timeframe: Baseline (Day -1 pre-dose) and Day 14, 28

Change from Baseline in hedonic response to sweet and high fat samples (self-rated hedonic preference assessment of sweetened dairy products)

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in ad libitum intake of snack foods (calories consumed by snack type)

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in ad libitum intake of snack foods (calories consumed by macronutrient content)

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in food ranking from buffet meals

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in requested food portion from buffet meal

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in calorie intake from buffet meal

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in 24-hour total energy intake by fat category

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in 24-hour total energy intake

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in Yale-Brown Obsessive Compulsive Scale modified for binge eating (Y-BOCS-BE)

Timeframe: Baseline (Day -2) and Day 13, 27

Change from Baseline in Three Factor Eating Questionnaire Revised 18 item (TFEQ-R18)

Timeframe: Baseline (Day -2) and Day 13, 27

Change from Baseline in Binge Eating Scale (BES) score

Timeframe: Baseline (Day -2) and Day 13, 27

Summary of Difference between pre- and post-buffet appetite visual analogue scales (A-VAS)

Timeframe: Up to Day 28

Summary of difference between pre- and post-ad-libitum snacking A-VAS

Timeframe: Up to day 28

Summary of A-VAS data for pre-grip force task

Timeframe: Up to day 28

Change from Baseline in Hunger, Craving and Fullness Questionnaire (HCFQ)

Timeframe: Baseline (Day -2) and Day 13, 27

Change from Baseline in mean duration time (milliseconds) from food processing task at Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in proportion of high-probability stimulus (percentage) from reward learning task at Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in mean duration time (milliseconds) from emotional processing task at Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in reaction time (milliseconds) from erotic stimuli task at Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in total area under curve (AUC) from temporal discounting (TD) Task on Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in attentional bias (milliseconds) from visual probe task (VPT) on Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in approach bias (milliseconds) from stimulus response compatibility task (SRC) on Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in normalized area under grip-force curve by image category on Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in temporal experience of pleasure scale (TEPS)

Timeframe: Baseline (Day -1) and Day 14, 28

Changes in sexual functioning questionnaire (CSFQ-14) from Baseline

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in fasting hormone levels: adrenocorticotrophic (ACTH) measured in peripheral venous blood

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in fasting hormone levels: leptin and adiponectin measured in peripheral venous blood

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in fasting hormone levels: total cortisol measured in peripheral venous blood

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in fasting hormone levels: ghrelin measured in peripheral venous blood

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in fasting hormone levels: insulin measured in peripheral venous blood

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in fasted glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in fasted C-peptide

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in fasted free fatty acids (FFA)

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in fasted glycosylated hemoglobin (HbA1c)

Timeframe: Baseline (Day -1) and Day 28

Twenty four hour urinary sucrose concentration

Timeframe: Up to Day 27

Cellular markers of opioid receptor activity: opioid receptor messenger ribonucleic acid (mRNA) expression and other markers were measured in peripherally circulating white blood cells (WBC)

Timeframe: Up to Day 28

Number of participants with adverse events (AE) and serious adverse events (SAE)

Timeframe: Approximately up to 49 days

Number of participants with abnormalities in electrocardiogram (ECG) data of potential clinical importance (PCI)

Timeframe: Day -7, -2, -1, 1, 13, 14, 27 and 28

Number of participants with abnormalities in vital signs data of PCI

Timeframe: Day -7, -2, -1, 1, 13, 14, 27 and 28

Number of participants with abnormalities in chemistry data of PCI

Timeframe: Day -7, -2, 13 and 27

Number of participants with abnormalities in hematology data of PCI

Timeframe: Day -7, -2, 13 and 27

Number of participants with abnormal urine microscopy-bacteria, cellular casts, granular casts and hyaline casts

Timeframe: Up to Day 27

Number of participants with abnormal urine microscopy-RBC and WBC

Timeframe: Up to Day 27

Number of participants with abnormal urine occult blood, glucose, ketones, nitrite and protein (dipstick)

Timeframe: Up to Day 27

Change from Baseline in power of attention score

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in digit vigilance reaction time

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in digit vigilance accuracy

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in choice reaction time

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in simple reaction time

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in rapid visual information processing reaction time

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in rapid visual information processing accuracy

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in immediate and delayed word recall data

Timeframe: Baseline (Day -1) and Day 14, 28

Change from Baseline in N-back reaction time on Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in N-Back accuracy on Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in interference scores from food and normal Stroop tasks on Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in Bond and Lader visual analogue mood scale (VAMS) on Day 28

Timeframe: Baseline (Day -1) and Day 28

Change from Baseline in Profile of Mood States-Brief (POMS –B) score on Day 1 and Day 28

Timeframe: Baseline (Day -1) and Day 1, 28

Change from Baseline Beck Depression Inventory (BDI-II) and Beck’s Anxiety Inventory (BAI) Total Scores on Day 1 and Day 28

Timeframe: Baseline (Day -1) and Day 1, 28

Number of participants with most severe suicidal behavior using Columbia Suicide Severity Rating Scale (C-SSRS)

Timeframe: Day 1 and 28

Change from Baseline Hospital Anxiety and Depression Scale (HADS) scores on Day 1 and Day 28

Timeframe: Baseline (Day -1) and Day 1, 28

Total Young Mania Rating Scale (YMRS) score – at screening and during treatment if indicated

Timeframe: Day 14 and 28

Summary of Barratt Impulsiveness Scale (BIS-11) score

Timeframe: Day -7

Summary of Behavioral Inhibition Scale/ Behavioral Activation Scale (BIS/BAS) score

Timeframe: Day -7

Summary of Empathy Quotient (EQ) from Cambridge Behavioral Scale score

Timeframe: Day -7

Area under the plasma concentration-time curve from time zero (pre-dose) to 24 hour post-dose (AUC 0-24 hour) on Days 1 and 28

Timeframe: Day 1 and 28 at pre-dose, 1, 2, 3, 6, 8, 12, 14 and 24.5 hours

Maximum observed plasma concentration (C-max) on Days 1 and 28

Timeframe: Day 1 and 28 at pre-dose, 1, 2, 3, 6, 8, 12, 14 and 24.5 hours

Time of occurrence of Cmax (T-max) on Days 1 and 28 and lag time before observation of drug concentrations in plasma (T-lag) on Day 1

Timeframe: Day 1 and 28 at pre-dose, 1, 2, 3, 6, 8, 12, 14 and 24.5 hours

The PK/PD relationships between GSK1521498 exposures and total energy intake

Timeframe: Baseline (Day -1) and Day 14, 28

Interventions:

Drug: GSK1521498

Drug: Placebo

Enrollment:

Primary completion date:

2011-27-05

Observational study model:

Not applicable

Time perspective:

Not applicable

Clinical publications:

S Chamberlain, K Mogg, B Bradley, A Koch, C Dodds, H Ziauddeen, W Tao, K Maltby, B Sarai, A Napolitano, D Richards, E Bullmore, P Nathan. Effects of Mu Opioid Receptor Antagonism on Cognition in Obese Binge-Eating Individuals . Psychopharmacology . 2012;224(4):501-509.

Samuel R Chamberlain, Pradeep J Nathan,Kay Maltby, Mark Bush, Wenli X Tao, Antonella Napolitano, Andrew L Skeggs, Allison C Brooke, Lucy G Cheke, Nicola S Clayton, I Sadaf Farooqi, Stephen O'Rahilly, Duncan B Richards, Paul C Fletcher, Edward T Bullmore,. Effects of the Mu-Opioid Receptor Antagonist GSK1521498 on Hedonic and Consummatory Eating Behaviour: A Proof of Mechanism Study in Binge Eating Obese Subjects. Molecular Psychiatry (2012). 2012;1-7.

Cambridge VC, Ziauddeen H, Nathan PJ, Subramanian N, Dodds C, Chamberlain SR, Koch A, Maltby K, Skeggs AL, Napolitano A, Sadaf Farooqi I, Bullmore ET, Fletcher PC. Neural and Behavioral effects of a novel mu opioid receptor antagonist in binge-eating obese people. Biol Psychiatry. 2013;73(9):887-894.

Medical condition

Obesity

Product

GSK1521498

Collaborators

Not applicable

Study date(s)

September 2010 to May 2011

Type

Interventional

Phase

Participation criteria

Sex

Female & Male

Age

18 - 60 years

Accepts healthy volunteers

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.

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.

Inclusion and exclusion criteria

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 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)

Exclusion criteria:

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.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Current or chronic history of neurological disorders.
A positive test for HIV or Hepatitis C.
Sleep apnoea
Gastrointestinal disease including inflammatory bowel disease, chronic diarrhea, Crohn’s or malabsorption syndromes within the past year
Participated in a clinical trial and has received an investigational product within 90 days.
Any contraindications or logistical complications anticipated in relation to Magnetic Resonance Imaging (MRI) scanning or other endpoint assessments, including: presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies, 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).
Special dietary requirements (e.g. vegetarians, vegans, religious, food–intolerant diets).
Unsuitable for cannulation.
Subjects planning to start a calorie controlled diet or major exercise routine.
Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication

Trial location(s)

Location

Status

Location

GSK Investigational Site

Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ

Status

Will Be Recruiting

Location

GSK Investigational Site

Birmingham, West Midlands, United Kingdom, B15 3ES

Status

Will Be Recruiting

Location

GSK Investigational Site

London, United Kingdom, NW10 7EW

Status

Will Be Recruiting

Study documents

Clinical study report

Available language(s): English

Download document(s)

Scientific result summary

Available language(s): English

Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status

Study complete

Actual primary completion date

2011-27-05

Actual study completion date

2011-27-05

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

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