EtOH Interaction Study

NCT ID: NCT00887367

Last Updated: 2017-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-29
• Study Completion Date: 2008-12-03

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.

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.

Conditions

Substance Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo to match GSK598809

Placebo to match GSK598809.

Group Type: PLACEBO_COMPARATOR

GSK598809

Intervention Type: DRUG

Two 175 mg doses of GSK598809 will be given.

Placebo to match ethanol infusion

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

Group Type: PLACEBO_COMPARATOR

Ethanol

Intervention Type: 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.

Interventions

GSK598809

Two 175 mg doses of GSK598809 will be given.

Intervention Type: DRUG

Ethanol

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 Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Leiden, , Netherlands

Countries

Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 22219221 (View on PubMed)

Other Identifiers

106591

Identifier Type: -

Identifier Source: org_study_id