A Single-blind, Randomised, Placebo-controlled, 15 Day Repeated-dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SB-649868 and Its Interaction With the CYP3A4 Isoenzyme in Healthy Male Subjects.
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- - SB649868 levels on days -7, 1, 4, 7 and 14 (pre-dose and post-dose)
Study Overview
Brief Summary
Subjects will be screened within 28 days, Simvastatin dose and single SB-649868 dose 10 and 7 days prior to repeat dosing respectively, 15 days SB-649868 repeat dosing with safety and cognition function tests.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy adult male subjects aged between 18 and 65 years of age inclusive.
- •Body weight =50 kg and BMI within the range 18.5-29.9 kg/m2 inclusive.
- •Healthy as judged by responsible physician. No clinically significant abnormality identified on the medical or laboratory evaluation and 12-lead ECG. A subject with a clinical abnormality or laboratory parameters outside the reference range for this age group may be included only if the Investigator and the Medical Monitor considers that the finding will not introduce additional risk factors and will not interfere with the study procedures.
- •Subjects will have blood pressure measurements within the normal range for healthy volunteers.
Exclusion Criteria
- •The subject has a positive pre-study urine drug/ alcohol urine screen.
- •A positive pre-study Hepatitis B surface antigen, Hepatitis C antibody, or HIV 1/2 result at the screening visit.
- •Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units.
- •Subject complains of sleep disturbances and/ or is receiving treatment for sleep disorders.
Arms & Interventions
Cohort 3
Subjects in Cohort 3 will be randomized to dose higher than that administered in Cohort 2 of SB-649868 or Placebo along with 10 mg of simvastatin.
Intervention: Simvastatin (Drug)
Cohort 1
Subjects in Cohort 1 will be randomized to receive 5 milligram (mg) of SB-649868 or Placebo along with 10 mg of simvastatin.
Intervention: SB-649868 (Drug)
Cohort 1
Subjects in Cohort 1 will be randomized to receive 5 milligram (mg) of SB-649868 or Placebo along with 10 mg of simvastatin.
Intervention: Placebo (Drug)
Cohort 1
Subjects in Cohort 1 will be randomized to receive 5 milligram (mg) of SB-649868 or Placebo along with 10 mg of simvastatin.
Intervention: Simvastatin (Drug)
Cohort 2
Subjects in Cohort 2 will be randomized to receive two or three times higher than the starting dose of SB-649868 or Placebo along with 10 mg of simvastatin.
Intervention: SB-649868 (Drug)
Cohort 2
Subjects in Cohort 2 will be randomized to receive two or three times higher than the starting dose of SB-649868 or Placebo along with 10 mg of simvastatin.
Intervention: Placebo (Drug)
Cohort 2
Subjects in Cohort 2 will be randomized to receive two or three times higher than the starting dose of SB-649868 or Placebo along with 10 mg of simvastatin.
Intervention: Simvastatin (Drug)
Cohort 3
Subjects in Cohort 3 will be randomized to dose higher than that administered in Cohort 2 of SB-649868 or Placebo along with 10 mg of simvastatin.
Intervention: SB-649868 (Drug)
Cohort 3
Subjects in Cohort 3 will be randomized to dose higher than that administered in Cohort 2 of SB-649868 or Placebo along with 10 mg of simvastatin.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
- SB649868 levels on days -7, 1, 4, 7 and 14 (pre-dose and post-dose)
Time Frame: on days -7, 1, 4, 7 and 14 (pre-dose and post-dose)
- Simvastatine and Beta-idroxy-simvastatine levels on days -10,1,4,7 and 15
Time Frame: on days -10,1,4,7 and 15
-AE, Lab values and cardiovascular monitoring after the SD and 14 days RD period (15 days)
Time Frame: after the SD and 14 days RD period (15 days)
Secondary Outcomes
- Cognitive functions, sleep profile and appetite assessment on days -7, 7 and 14.(on days -7, 7 and 14.)