GSK1521498 Alcohol Interaction Study

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to assess the safety and tolerability of GSK1521498 in combination with alcohol and to determine the amount of GSK1521498 and alcohol in your blood after you have been given these together. The study will also determine whether GSK1521498 will have an effect on alcohol liking and consumption.

Detailed Description
-----------------
The study is to test a new drug which may be used for treating alcohol addiction. The drug works by inhibiting the effects of messenger molecules called opioids. These opioids are naturally produced within the human body, and are involved in controlling how much alcohol we drink and the pleasure we get from drinking alcohol. We believe that GSK1521498 might be effective in the treatment of alcohol addiction because it is well known that drugs working on similar binding sites in the brain reduce the pleasure we get from drinking alcohol. As alcohol can effect the way that a drug is metabolised in the body, The investigators need to determine that it is safe to take GSK1521498 in combination with alcohol. and to determine the amount of GSK1521498 and alcohol in your blood after you have been given these together. The study will also determine whether GSK1521498 will have an effect on alcohol liking and consumption.

Official Title
-----------------
A Randomised, Double-Blind, Single-Dose, Four-Period Cross-Over Study to Determine the Effects of Alcohol on the Pharmacokinetics and Pharmacodynamics of GSK1521498 in Healthy Subjects

Conditions
-----------------
Alcoholism

Intervention / Treatment
-----------------
* Drug: GSK1521498
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: healthy male or female between 21 and 55 years of age inclusive. within 20% normal weight for height and body build. A female subject of child-bearing potential must use one of the contraception methods listed in the protocol prior to the start of the study until at least 14 days after receiving the last dose of study medication. Male subjects must agree to use one of the contraception methods listed in the protocol from the time of the first dose of study medication until at least 5 days after receiving the last dose of study medication. History of regular alcohol consumption within 6 months of study. No recent changes in patterns of alcohol consumption. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Exclusion Criteria: A positive test for HIV, Hep B or Hep C. Current or chronic history of liver disease. Current or chronic history of neurological disorders. Subjects with previous or current psychiatric history. Past history of DSM-IV alcohol dependence or abuse. Binge drinking more than once a week (>5 standard drinks in one session is a binge). Currently trying to quit alcohol. Positive urine screen for amphetamines, barbiturates, cocaine, opiates, cannabinoids or bezodiazepines at screening. Regular consumption of >450mg caffeine per day (an average cup contains about 75mg). Heavy smokers, defined as those who smoke >10 cigarettes a day. Also those who cannot abstain during the admission period. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 14 days prior to the first dose of study medication. Pregnant or lactating females. QTcB or QTcF >450msec. Participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product. Where participation in the study would result in donation of blood or blood products in excess of 500mL within a 56 day period.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1521498 &amp; alcohol<br>GSK1521498 20 mg and alcohol (0.5g/kg ethanol mixed with orange juice) | Drug: GSK1521498<br>* GSK1521498 20 mg administered with alcohol to determine PK/PD interactions<br>|
| Experimental: GSK1521498 & orange juice<br>GSK1521498 20 mg and orange juice approximately matching alcoholic beverage for volume and colour | Drug: GSK1521498<br>* GSK1521498 20 mg administered with alcohol to determine PK/PD interactions<br>|
| Experimental: Placebo &amp; alcohol<br>Placebo and alcohol (0.5g/kg ethanol mixed with orange juice) | Other: Placebo<br>* Placebo<br>|
| Placebo Comparator: Placebo &amp; orange juice<br>Placebo and orange juice approximately matching alcoholic beverage for volume and colour | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic interaction | AUC and Cmax of GSK1521498 and alcohol | GSK1521498 PK sampling; pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 13, 24, 48 and 72 hr post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: adverse events, vital signs, ECGs, physician/nurse observations, safety lab tests, mood assessments |  | 3 Months | 
| Neurological assessments including Purdue Pegboard test |  | 3 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pharmacokinetics, mu-opioid receptors, Addiction, Pharmacodynamics, Alcohol