A Human Volunteer Study Investigating Single Oral Doses of GSK598809 in Otherwise Healthy Smokers

Study Overview
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Brief Summary
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Study to investigate the safety, tolerability and pharmacokinetics of GSK598809 in otherwise healthy volunteers. This study is required because this drug is being developed for the treatment of nicotine dependence. It is important to evaluate how this drug interacts in healthy smokers. The study is planned to consist of a single part, with 4 dosing periods. Subjects will receive 3 escalating doses of GSK598809 and 1 dose of placebo. There will be at least 1 week of wash out between doses. In each dosing period 14 subjects will receive escalating doses and 4 subjects will receive placebo. The actual doses used will be determined based on the safety/ tolerability and pharmacokinetics during the previous dose. It is expected that the duration of this study will be approximately 10 weeks.

Official Title
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A Placebo-controlled, Single-blind, Randomised, Human Volunteer Study Investigating the Tolerability and Pharmacokinetics of Escalating Single Oral Doses (75mg and Above) of GSK598809 in Otherwise Healthy Smokers

Conditions
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Substance Dependence

Intervention / Treatment
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* Drug: GSK598809
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion: A healthy man or woman 18 - 50 years old Neither too fat, nor too thin Female subjects must use an acceptable method of contraception from the first dose of study medication until 90 days following the final follow-up visit. Female subjects must not be breast feeding and should not have been breast feeding for a month. Male subjects must agree to use an acceptable method of contraception from the first dose of study medication until 90 days following the final follow-up. Subjects need to smoke 20 - 40 cigarettes a day inclusive for at least the past year and to not have tried to quit in the 3 months before the start of the study. Exclusion: Any current medical or psychiatric illness Any history of chronic medical or psychiatric illnesses Previous or current alcohol or drug abuse/dependence including nicotine Personal or family history of prolonged QTc syndrome

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects receiving treatment sequence ABCD<br>Subjects will receive treatment sequence ABCD; A= placebo, B= GSK598809 dose 1 (75 milligrams), C = GSK598809 dose 2, and D = GSK598809 dose 3. | Drug: GSK598809<br>* GSK598809 capsules will be available with dose strengths of 5 milligrams and 25 milligrams, administered orally with water.<br>Drug: Placebo<br>* Placebo capsules will be administered orally with water.<br>|
| Experimental: Subjects receiving treatment sequence BACD<br>Subjects will receive treatment sequence BACD; B= GSK598809 dose 1 (75 milligrams), A= placebo, C = GSK598809 dose 2 and D = GSK598809 dose 3 | Drug: GSK598809<br>* GSK598809 capsules will be available with dose strengths of 5 milligrams and 25 milligrams, administered orally with water.<br>Drug: Placebo<br>* Placebo capsules will be administered orally with water.<br>|
| Experimental: Subjects receiving treatment sequence BCAD<br>Subjects will receive treatment sequence BCAD; B= GSK598809 dose 1 (75 milligrams), C = GSK598809 dose 2, A= placebo and D = GSK598809 dose 3. | Drug: GSK598809<br>* GSK598809 capsules will be available with dose strengths of 5 milligrams and 25 milligrams, administered orally with water.<br>Drug: Placebo<br>* Placebo capsules will be administered orally with water.<br>|
| Experimental: Subjects receiving treatment sequence BCDA<br>Subjects will receive treatment sequence BCDA; B= GSK598809 dose 1 (75 milligrams), C = GSK598809 dose 2, D = GSK598809 dose 3 and A= placebo. | Drug: GSK598809<br>* GSK598809 capsules will be available with dose strengths of 5 milligrams and 25 milligrams, administered orally with water.<br>Drug: Placebo<br>* Placebo capsules will be administered orally with water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: Clinical labs, cardiovascular variables, vital signs, adverse events over 48 hours post dosing and at follow up. Psychological assessment and movement scales will be monitored. Blood Sampling over 48 hours. |  | 48 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cigarette craving assessed over 24 hours around dosing. Cigarette Consumption to be monitored during the whole study.Withdrawal from nicotine assessed during first four hours of dosing. Cognition/ impulsivity assessed over 24 hours after dosing. |  | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tolerability, dose escalation, GSK598809, Pharmacodynamics, Safety, single, placebo, Smokers, Pharmacokinetics