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Effects of Repeat Dosing of GSK1521498

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00976105
First received: September 11, 2009
Last updated: January 27, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Obesity
Drug: Zolpidem or placebo - Hypnotic drug given for sleep disorders
Drug: GSK1521498 or placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of 10 Days of Repeat Dosing of GSK1521498 in Overweight or Obese But Otherwise Healthy Subjects.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety and tolerability: adverse events, blood pressure, heart rate, ECG, clinical chemistry, heamatology, urinalysis, change in reaction times, change in mood scales [ Time Frame: During 10 days of repeat dosing ] [ Designated as safety issue: Yes ]
  • Obtain benchmarking data on the cognitive and mood changes induced by a single dose of up to 10mg zolpidem [ Time Frame: Single occasion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: On Day 1 and/or following 10 days of repeat dosing and trough samples on Day 5, 7, 8, 9 and 10 ] [ Designated as safety issue: Yes ]
  • PK/PD relationships: cognitive and mood changes, pressure pain threshold and tolerance, heat pain threshold [ Time Frame: During 10 days of reapeat dosing ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: Screening, or Day -1 and Day 10 ] [ Designated as safety issue: No ]

Enrollment: 49
Study Start Date: September 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Part A: Zolpidem or placebo
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
The information gathered from Part A will be used as a benchmark against which any effects of GSK1521498 can be assessed in Part B.
Experimental: Part B: GSK1521498 or placebo
At least 15 hours after Part A is completed subjects will enter Part B of the study.
Drug: GSK1521498 or placebo
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.

Detailed Description:

This study is to test a new drug which may be used for treating eating behaviour and patterns that some overweight and obese patients find difficult to control. The drug works by inhibiting the effects of messenger molecules called opioids, e.g. endorphins. These opioids are naturally produced within the human body and control hunger, thirst, and the pleasurable feelings we relate to eating food. The drug attaches to opioid binding sites in the brain, known as mu-opioid receptors; this blocks the natural effect of opioids which may reduce the craving to eat fatty or sugary foods. Single doses of the drug have been given to humans and showed it was safe. Now the drug will be given every day for 10 days to check that the drug is safe and tolerated when given repeatedly. The study is in two parts:

Part A: people will receive a sleeping tablet to make them sleepy (or a dummy drug) and will complete some questionnaires and simple tests including computer exercises to test the effect of this tablet on mood and cognition. This information will be used to help judge what is happening in Part B.

Part B: requires staying in the unit for 10 days to receive a tablet every day and complete questionnaires and other tests to check for any mood and cognitive changes. Various other assessments will include effects on eating behaviour, pain measures and changes in body composition (content of fat, muscle and water).

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that contraindicates participation.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Unwillingness or inability to follow the procedures outlined in the protocol, including abstaining from consumption of caffeine-or xanthine containing products for 24 hours prior to dosing until the post-dose assessment, use of illicit drugs, refrain from alcohol for 24 hours prior to dosing until final post-dose assessment,, consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until after collection of the final pharmacokinetic blood sample.
  • Any finding that would preclude safe use of Echo MRI scanning. These include: a history of panic attacks and/or claustrophobia, pacemaker, implanted hearing aid, metallic body piercing and/or other metal implants that cannot be removed, the opinion of the Investigator the subject exceeds size limitations for the instrument.
  • Mentally or legally incapacitated
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00976105

Locations
United Kingdom
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00976105     History of Changes
Other Study ID Numbers: 111849
Study First Received: September 11, 2009
Last Updated: January 27, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
Pharmacokinetics
Pharmacodynamics
Safety and tolerability
Repeat dose
Personality traits
Fat mass
Healthy volunteers

Additional relevant MeSH terms:
Zolpidem
Central Nervous System Agents
Central Nervous System Depressants
GABA Agents
GABA Agonists
GABA-A Receptor Agonists
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014