Safety, Tolerability and Pharmacokinetics of Repeat Doses of GSK1014802.

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00908154
First received: May 7, 2009
Last updated: May 29, 2009
Last verified: May 2009
  Purpose

GSK1014802 is a use-dependent sodium channel blocker and an effective anticonvulsant in animal models.

This study is being conducted to obtain information regarding the safety, tolerability and pharmacokinetics of repeated doses of GSK1014802 administered for up to 28 days in healthy male or female subjects. In addition, the effect of food on the pharmacokinetics of GSK1014802 will be investigated.


Condition Intervention Phase
Bipolar Depression
Bipolar Disorder
Drug: Placebo
Drug: GSK1014802
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Single-Blind, Randomised, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Repeat Doses of GSK1014802 and Its Interaction With Food in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety and tolerability will be evaluated by monitoring AEs and concomitant medication, ECG, Lead II monitoring, Holter monitoring, vital signs, and laboratory parameters. [ Time Frame: 14-28 days ] [ Designated as safety issue: Yes ]
  • Blood concentrations of GSK1014802 following a single oral dose of GSK1014802. [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • Blood concentrations of GSK1014802 following repeated oral doses of GSK1014802 given once daily or twice daily and their relationship with the GSK1014802 exposure after a single dose. [ Time Frame: 14-28 days ] [ Designated as safety issue: No ]
  • Blood concentrations of GSK1014802 following repeated oral doses of GSK1014802 given once daily with or without food. [ Time Frame: 14-28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bond-Lader VAS scale [ Time Frame: 14-28 days ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: May 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Cohort 1 Drug: Placebo
Tablets to match GSK1014802
Drug: GSK1014802
Sodium channel blocker
Cohort 4 Drug: Placebo
Tablets to match GSK1014802
Drug: GSK1014802
Sodium channel blocker
Cohort 3 Drug: Placebo
Tablets to match GSK1014802
Drug: GSK1014802
Sodium channel blocker
Cohort 2 Drug: Placebo
Tablets to match GSK1014802
Drug: GSK1014802
Sodium channel blocker

Detailed Description:

GSK1014802 is a use-dependent sodium channel blocker and an effective anticonvulsant in animal models.

This study is being conducted to obtain information regarding the safety, tolerability and pharmacokinetics of repeated doses of GSK1014802 administered for up to 28 days in healthy male or female subjects. In addition, the effect of food on the pharmacokinetics of GSK1014802 will be investigated.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.

    • Male or female (of non-child bearing potential) subjects aged between 18 and 55 years.
    • A female subject is eligible to participate if she is of non-childbearing potential.
    • Male subjects must agree to use an acceptable form of contraception.
    • Body weight ≥ 50 kg and BMI within the range 19 - 29.9 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; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

  • The subject has a positive pre-study drug/alcohol screen.

    • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
    • A positive test for HIV antibody.
    • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females).
    • Current or past history of symptomatic orthostatic hypotension or history of unexplained vasovagal episode(s).
    • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives (60 h) or twice the duration of the biological effect of the investigational product (whichever is longer).
    • 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 (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication.
    • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their 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.
    • Pregnant females.
    • Lactating females.
    • Unwillingness or inability to follow the procedures outlined in the protocol.
    • History of sensitivity to heparin or heparin-induced thrombocytopenia.
    • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
    • . Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
    • History of known or suspected seizures, including infantile febrile, unexplained significant and recent loss of consciousness or history of significant head trauma with loss of consciousness or a family history (first degree relative) of epilepsy or seizures (fits).
  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: NCT00908154

Locations
United Kingdom
GSK Investigational Site
London, United Kingdom, SE1 1YR
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00908154     History of Changes
Other Study ID Numbers: 107727, SCB107727
Study First Received: May 7, 2009
Last Updated: May 29, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
sodium channel blocker
bipolar disorder
repeat dose

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Sodium Channel Blockers
Diuretics, Potassium Sparing
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Diuretics
Natriuretic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014