EtOH Interaction Study
Condition: Substance Dependence
MeSH terms: Substance-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will investigate the possible effects of alcohol in combination with GSK598809 on
      the central nervous system in 20 healthy male and female volunteers, between 18 and 65 years
      of age.

      During 4 separate study periods subjects will receive the following treatment combinations:
      Alcohol + GSK598809, alcohol + placebo drug, placebo infusion + GSK598809, and placebo
      infusion + placebo drug. A placebo is a pill or liquid infusion which contains no drug or
      alcohol; it is a dummy version. Therefore it is administered in the same way that either the
      study drug or ethanol is depending on which placebo it is. All study drugs are administered
      in a random order and both the doctor and the participant are not aware of the treatment
      combination. However treatment combinations will be available at the end of the study or in
      case of an emergency. GSK598809 is administered orally and alcohol is administered per
      infusion. The duration of the infusion is 5 hours, during which approximately 75 grams of
      alcohol is infused, which is comparable to less than one bottle of wine.
    

Detailed description: 
      This is a blinded, randomised, placebo-controlled, double-dummy, four-period crossover study
      to investigate the psychomotor and cognitive effects of GSK598809 alone and in combination
      with ethanol in healthy subjects.

      A sufficient number of subjects, approximately 20 healthy (18 to 65 years) male and female
      subjects will be enrolled. Occasional smokers who are non-daily smokers may be enrolled in
      the study, but will not be permitted to smoke whilst in the unit.

      Subjects will be screened by medical history, physical examination and routine laboratory
      tests within three weeks before the start of the study. Within three weeks or on Day -1 they
      will have a training session to get familiar with the pharmacodynamic tests.

      There will be four crossover sessions. All study occasions/sessions will be performed in the
      same way. The duration of each treatment session is 5 study days. Subjects will report to the
      clinic during the evening of Day -1 in a fasted condition and will remain in the clinic for
      two overnight stays. A short study introduction will be given followed by admission
      procedures. Dinner will be served after the collection of blood samples for laboratory safety
      tests.

      On morning of study day 1, approximately 08:00hrs two intravenous cannulae (one cannula for
      blood sampling and another cannula for infusion of the ethanol/placebo) will be inserted.
      Before the start of the infusion a light breakfast will be given. The alcohol infusion will
      start in the morning, between approximately 09:30hr and 10:00hr and will take place for five
      hours, followed by a three-hour infusion-free washout period. GSK598809 or matching placebo
      will be administered orally 30 minutes after the start of the alcohol infusion. A
      standardised lunch will be given at approximately 3.5 hours post dose and dinner
      approximately 9 hours post dose.

      Subjects will be discharged after the completion of study assessments and AE review on Day 2
      and if deemed appropriate by the investigator or designee. Study Days: 3 and 4 will be
      outpatient visits for collection of pharmacokinetic samples and AE review.

      During each session, a range of central nervous system (CNS) functions will be tested
      frequently, using a validated CNS-battery, CHDR Neurocart. In addition, pharmacokinetic
      measurements will be taken for plasma levels of GSK598809 and GSK685249 (GSK598809
      metabolite). Pharmacokinetic measures will also be taken for breath alcohol and blood alcohol
      levels.

      There will be a washout period of at least five days between treatment sessions. The follow
      up visit will take place approximately 7 days post final treatment.
    

Intervention name(s): GSK598809; Ethanol
Intervention type(s): Drug; Other
Intervention description(s): Two 175 mg doses of GSK598809 will be given.; A constant ethanol level of 0.6 g·L-1 for five hours will be given to the subjects intravenously. This level shows significant CNS effects, without causing too many inadvertent events. Furthermore this level is considered safe as it is just above the legal driving limit in the Netherlands (i.e. 0.5 g·L-1) and these levels are routinely achieved during social drinking. Moreover, this level leaves enough room for CNS-impairment without compromising safety, in case of a (supra-) addictive drug-alcohol interaction.
Intervention MeSH terms: Ethanol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Healthy volunteers; Substance dependence; Alcohol dependence