GSK2018682 FTIH in Healthy Volunteers

Study Overview
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Brief Summary
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This protocol describes the first administration of GSK2018682 to humans. The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of GSK2018682. The study will also provide preliminary evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on total lymphocyte counts.

Detailed Description
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This protocol describes the first administration of GSK2018682 to humans. The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of GSK2018682. The study will also provide preliminary evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on total lymphocyte counts.

Official Title
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A Single-blind, Placebo-controlled, Two Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Doses of GSK2018682 in Healthy Volunteers

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: GSK2018682
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters significantly outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with lymphocyte counts outside the normal range should always be excluded from enrollment BMI within the range 19 - 28 kg/m2 (inclusive). Exclusion Criteria: A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). A positive pre-study drug/alcohol screen. A positive test for HIV antibody. History of regular alcohol consumption Subjects with a history of, or examination suspicious for, skin cancer(s) including melanoma, basal cell or squamous cell carcinoma. Systolic blood pressure less than 95 mmHg or greater than 140 mmHg, or diastolic blood pressure less than or equal to 50 mmHg or greater than or equal to 95 mmHg. Symptomatic reduction in blood pressure after orthostatic challenge. Subjects with resting heart rate less than 45 beats per minute or greater than 90 beats per minute Other criteria may apply as defined by the clinical protocol.

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 |
| --- | --- |
| Experimental: Part A<br>Part A will be used to confirm the prediction of GSK2018682 PK, assess its effects on lymphocytes, and monitor its safety profile in a single cohort (Cohort 1). Cohort 1 will consist of 4 subjects and explore 4 doses of GSK2018682 in 4 study sessions. In each session, three subjects will receive GSK2018682 and one subject will receive placebo. Thus, when the cohort completes, each subject will receive placebo and 3 doses of GSK2018682. | Drug: GSK2018682<br>* GSK2018682<br>Drug: Placebo<br>* Matched Placebo<br>|
| Experimental: Part B<br>Part B will explore doses to refine the dose-response curve of GSK2018682 on lymphocyte suppression, as allowed by stopping criteria, in 1 or 2 cohorts of up to 15 subjects (Cohort 2 and Cohort 3). In Part B, up to six single ascending doses of GSK2018682 and one dose of placebo will be investigated in up to 8 sessions. | Drug: GSK2018682<br>* GSK2018682<br>Drug: Placebo<br>* Matched Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the safety and tolerability of single escalating oral doses of GSK2018682 | Adverse event and safety lab monitoring | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 12 weeks | 
| To investigate effects of GSK2018682 on heart rate and blood pressure | 12 lead ECG and telemetry monitoring plus vital signs (systolic and diastolic blood blood pressures), heart rate, respiratory rate and temperature | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 12 weeks | 
| To investigate the pharmacokinetics of single doses of GSK2018682 | Peak blood concentration, time of peak blood concentration, oral clearance, half life and AUC | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 12 weeks | 
| Evaluate the effect of single escalating oral doses of GSK2018682 on lymphocytes (totals plus subsets) | Reduction from baseline in lymphocyte counts obtained at different time points after dosing and at different dose levels | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK2018682, First Time in Human, Healthy Volunteer