EtOH Interaction Study

NCT00887367 | Completed Phase 1

• 1 other identifier: 106591
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Substance Dependence

Keywords

Healthy volunteers; Substance dependence; Alcohol dependence

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability: Vital sign measurement, 12 lead ECG and telemetry, safety laboratory sampling including prolactin and lipid measurements, Barnes Akathesia Scale (BAS), Simpson-Angus Scale (SAS) and Abnormal Involuntary Movement Scale (AIMS).

  Screening: BAS, SAS and AIMS (as training only), 12 lead ECG, vital signs and clinical labs. All will be measured throughout dosing day (Day 1), day 2, 3: vital signs, day 4: vital signs, clinical labs, follow up: clinical labs, vital signs, 12 lead ECG

• Pharmacokinetics: breath ethanol concentrations, blood ethanol concentrations, main pharmacokinetic parameters of GSK598809 and its metabolite (GSK685249) AUC∞, Cmax, Tmax and t½.

  All will be measured throughout day 1, PK blood sampling for GSK598809 and GSK685249 will also be collected on Day 2, 3 and 4.

• Pharmacodynamic: saccadic eye movements, smooth pursuit eye movements, body sway, adaptive tracking, Visual Verbal Learning Test (VVLT).

  Saccadic eye movement, smooth pursuit eye movements, body sway and adaptive tracking measured at set intervals between 1.5hrs pre dose to 7.5hrs post dose. VVLT administered between 0.5hrs post dose to 3.5hrs post dose.

Secondary Outcomes (1)

• Pharmacodynamic/biomarker endpoints: saccadic eye movements, visual analogue scales (VAS B&L) according to Bond & Lader, Visual Analogue Scales for 'alcohol effects' (VAS 'Alcohol Effects').

  Saccadic eye movements at time points as given above. VAS B&L and VAS 'Alcohol Effects' at following time points: -1.5, 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 7.5 hrs post dose.

Study Arms (2)

Placebo to match GSK598809

PLACEBO COMPARATOR

Placebo to match GSK598809.

Drug: GSK598809

Placebo to match ethanol infusion

PLACEBO COMPARATOR

Glucose solution to be given in the same way as ethanol.

Other: Ethanol

Interventions

GSK598809 DRUG

Two 175 mg doses of GSK598809 will be given.

Placebo to match GSK598809

Ethanol OTHER

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.

Placebo to match ethanol infusion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Generally healthy.
• Occasional non-daily smokers.
• Willing to use appropriate contraception method.
• Weight more than 50 kg.
• BMI within the range 18 - 30 kg/m2.

You may not qualify if:

• Pregnant or breast feeding female.
• Daily smoker.
• Asthma or a history of asthma.
• Abuse of drugs or alcohol.
• Psychiatric illness.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Leiden, 2333 CL, Netherlands

Location

Related Publications (1)

• te Beek ET, Zoethout RW, Bani MS, Andorn A, Iavarone L, Klaassen ES, Fina P, van Gerven JM. Pharmacokinetics and central nervous system effects of the novel dopamine D3 receptor antagonist GSK598809 and intravenous alcohol infusion at pseudo-steady state. J Psychopharmacol. 2012 Feb;26(2):303-14. doi: 10.1177/0269881111431750. Epub 2012 Jan 4.

  PMID: 22219221 BACKGROUND

Related Links

• Results for study 106591 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Substance-Related Disorders; Alcoholism

Interventions

GSK598809; Ethanol

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders; Alcohol-Related Disorders

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2009
• First Posted: April 24, 2009
• Study Start: September 29, 2008
• Primary Completion: December 3, 2008
• Study Completion: December 3, 2008
• Last Updated: July 18, 2017

Record last verified: 2017-07

Locations

NL (1)