Substance DependencePhase 1NCT00887367
EtOH Interaction Study
A Phase 1 study testing GSK598809 and Ethanol in people with Substance Dependence, run by GlaxoSmithKline at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Substance Dependence
- What is being tested?
- GSK598809 and Ethanol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- 29 Sep 2008to 3 Dec 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Pregnant or breast feeding female.
- Daily smoker.
- Asthma or a history of asthma.
- Abuse of drugs or alcohol.
- Psychiatric illness.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Study to Investigate Potential Interactions Between GSK598809 and Ethanol in Healthy Subjects
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.
Read the 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
- Being tested
- GSK598809, Ethanol
- Keywords
- Healthy volunteers, Substance dependence, Alcohol dependence
- Medical subject headings
- Substance-Related Disorders, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK598809Drug
Two 175 mg doses of GSK598809 will be given.
EthanolOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo to match GSK598809 | Placebo comparator | Placebo to match GSK598809. Receives: Drug: GSK598809 |
| Placebo to match ethanol infusion | Placebo comparator | Glucose solution to be given in the same way as ethanol. Receives: Other: Ethanol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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).
Measured: 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').
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2009 (estimated)
- Study start29 Sep 2008
- Primary completion3 Dec 2008
- Study completion3 Dec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Substance DependenceStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00887367
- Sponsor's protocol ID
- 106591
- Status last verified
- Jul 2017
- First submitted
- 23 Apr 2009
- Last updated
- 18 Jul 2017
- Results posted
- No
Publications
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.
PubMed 22219221
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Investigate Potential Interactions Between GSK598809 and Ethanol in Healthy Subjects
- ClinicalTrials.gov ID
- NCT00887367
- Acronym / sponsor ID
- 106591
- Conditions
- Substance Dependence
- Keywords
- Healthy volunteers, Substance dependence, Alcohol dependence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 29 Sep 2008 (actual)
- Primary completion
- 3 Dec 2008 (actual)
- Study completion
- 3 Dec 2008 (actual)
- First posted
- 24 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo to match GSK598809 | Placebo comparator | Drug: GSK598809Placebo to match GSK598809. |
| Placebo to match ethanol infusion | Placebo comparator | Other: EthanolGlucose solution to be given in the same way as ethanol. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- Pregnant or breast feeding female.
- Daily smoker.
- Asthma or a history of asthma.
- Abuse of drugs or alcohol.
- Psychiatric illness.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK598809Two 175 mg doses of GSK598809 will be given. | Drug | Placebo to match GSK598809 |
| EthanolA 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. | Other | Placebo to match ethanol infusion |
Primary outcome
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).
Time frame: 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.
Time frame: 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).
Time frame: 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.
1 secondary outcome
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').
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2017.
- Background: PubMed 22219221te 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.
- Results for study 106591 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK598809 and Ethanol in people with Substance Dependence, run by GlaxoSmithKline at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00887367, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2017.