Safety, Tolerability and Pharmacokinetics of GSK1034702 in Healthy Subjects

Study Overview
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Brief Summary
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This is a First Time in Human Study to assess the safety, tolerability and pharmacokinetics of single doses of GSK1034702 in healthy subjects. It will be a single-blind, randomized, placebo-controlled, single oral dose, dose-rising, cross-over study in healthy male and female (of non-child bearing potential) subjects. Subjects will be randomized into cohorts of 10 subjects and cohorts will be recruited until the pre-defined safety or PK stopping limits are reached. Each subject will receive placebo and up to 4 doses of GSK1034702 in a randomized sequence on 5 separate study occasions.

Official Title
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Single-blind, Randomised, Placebo Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK1034702 in Healthy Subjects

Conditions
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Cognitive Disorders

Intervention / Treatment
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* Drug: GSK1034702
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy as determined by a responsible physician, based on a medical evaluation including own and familial medical history, physical examination, laboratory tests and cardiac monitoring. Male or female between 18 and 55 years of age. A female subject is eligible to participate if she is of non-childbearing potential Body weight > 50 kg and BMI within the range 19 - 29.9 kg/m2 (inclusive). Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Capable of reading, comprehending and writing English at a sufficient level to complete study-related materials. Demonstrates no evidence of mental impairment. No co-morbid Psychiatric Disorders as defined using the Mini International Neuropsychiatric Interview Exclusion Criteria: A positive pre-study drug/alcohol screen. A positive pre-study Hepatitis B , Hepatitis C or HIV. History of regular alcohol consumption. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). Exposure to more than four new chemical entities within 12 months prior to the first dosing day. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements . History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. Pregnant females, females planning pregnancy or lactating females. Unwillingness or inability to follow the procedures outlined in the protocol. History of sensitivity to heparin or heparin-induced thrombocytopenia. Subjects with a current or a history of psychiatric illness. Subjects with any history of suicidal attempts or behavior. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products. Consumption of red wine, seville oranges, grapefruit or grapefruit juice (and pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices) from 7 days prior to the first dose of study medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1<br>Subjects will be receive GSK1034702 0.5 milligram (mg) following the dose escalation plan | Drug: GSK1034702<br>* Oral or liquid<br>Drug: Placebo<br>* To match GSK1034702<br>|
| Other: Cohort 2<br>Subjects will be receive GSK1034702 5 mg following the dose escalation plan | Drug: GSK1034702<br>* Oral or liquid<br>Drug: Placebo<br>* To match GSK1034702<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| •Safety and tolerability determined by adverse events; ECG; Holter; blood pressure, heart rate, respiration rate; clinical laboratory evaluations, pupil size & temperature.•Blood concentrations of GSK1034702. |  | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the Bond-Lader Visual Analogue Scale. |  | 20 weeks | 
| Assessment of exploratory PD markers: neuroendocrine markers, e.g. growth hormone. |  | 20 weeks | 
| Relationship between GSK1034702 plasma concentrations and safety/tolerability or exploratory PD endpoints with selected pharmacodynamic and safety parameters. |  | 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, M1 receptor agonist, safety, pharmacokinetics, GSK1034702