Effects of Repeat Dosing of GSK1521498

NCT00976105 | Completed Phase 1

• 1 other identifier: 111849
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

The overall purpose of this study is to see whether the drug is safe and well tolerated when given to overweight or obese but otherwise healthy volunteers for 10 days. Up to 4 groups of people will be given the drug at variable strengths. The blood levels of the drug will be measured and the effects on mood and cognition (the mental processes involved in awareness, learning and judgement) will be assesed.

Conditions

Obesity

Keywords

Pharmacokinetics; Pharmacodynamics; Safety and tolerability; Repeat dose; Personality traits; Fat mass; Healthy volunteers

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability: adverse events, blood pressure, heart rate, ECG, clinical chemistry, heamatology, urinalysis, change in reaction times, change in mood scales

  During 10 days of repeat dosing

• Obtain benchmarking data on the cognitive and mood changes induced by a single dose of up to 10mg zolpidem

  Single occasion

Secondary Outcomes (3)

• Assess accumulation, dose proportionality and pharmacokinetics of GSK1521498: AUC (0-24), Cmax, tmax, tlag (Dose 1 only), t1/2 (Dose 10 only), trough plasma concentrations on Day 5, 7, 8, 9 and 10

  On Day 1 and/or following 10 days of repeat dosing and trough samples on Day 5, 7, 8, 9 and 10

• PK/PD relationships: cognitive and mood changes, pressure pain threshold and tolerance, heat pain threshold

  During 10 days of reapeat dosing

• Assess effects on body weight, fat mass, eating behaviour and personality traits: Bodyweight and BMI, Fat mass (ECHO-MRI), food ingested and energy intake, eating behaviour and persoality scales: Y-BOC-BE, BE, TFEQ and BIS

  Screening, or Day -1 and Day 10

Study Arms (2)

Part A: Zolpidem or placebo

ACTIVE COMPARATOR

This part is designed to examine the acute effects of up to 10mg of a known hypnotic sedative drug (Zolpidem) on cognitive and mood changes sensitve to sedation and tiredess.

Drug: Zolpidem or placebo - Hypnotic drug given for sleep disorders

Part B: GSK1521498 or placebo

EXPERIMENTAL

At least 15 hours after Part A is completed subjects will enter Part B of the study.

Drug: GSK1521498 or placebo

Interventions

Zolpidem or placebo - Hypnotic drug given for sleep disorders DRUG

The information gathered from Part A will be used as a benchmark against which any effects of GSK1521498 can be assessed in Part B.

Part A: Zolpidem or placebo

GSK1521498 or placebo DRUG

The first group will start at a low dose (10 mg GSK1521498 or placebo) for 10 days. The study team will then assess the data gathered from the first cohort and will select the dose that the next cohort will receive for 10 days. There will be up to 4 cohorts.

Part B: GSK1521498 or placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy as determined by a responsible and experienced physician
• Non smoking male or female between 18 and 60 years of age inclusive
• A female subject of child-bearing potential must use a contraception method listed in the protocol prior to the start of dosing 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 first dose of study medication until at least 84 days after receiving the last dose of study medication.
• BMI within the range 25 - 35 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• QTcB or QTcF \< 450 msec.
• Suitable for repeat cannulation.

You may not qualify if:

• Has clinically significant rhythm abnormalities identified during 24-hour screening Holter assessment.
• Systolic blood pressure greater than 150 mmHg and/or diastolic BP greater than 90 mmHg.
• Diabetes mellitus or physician-diagnosed dyslipidaemia requiring treatment
• Self-administered Beck Depression Inventory II scale total score greater than 13 or suicide question score greater than zero at screening.
• Positive pre-study drug/alcohol screen
• Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• Positive test for HIV antibody.
• Pregnant or lactating females
• Smoking history that includes regular use of tobacco or nicotine-containing products within 6 months prior to screening.
• A history of any thyroid dysfunction or an abnormal thyroid function test
• History of regular high level of alcohol consumption within 6 months of the study
• Participated in a clinical trial involving an investigational product within 90 days
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days prior to the first dose of study medication
• History of any gastrointestinal or hepatic conditions or procedures that could affect absorption of the investigational product.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

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.
• Results for study 111849 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Obesity

Interventions

Zolpidem; 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; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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 11, 2009
• First Posted: September 14, 2009
• Study Start: September 22, 2009
• Primary Completion: March 9, 2010
• Study Completion: March 9, 2010
• Last Updated: June 20, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)