To Estimate the Potential Effects of Repeat Doses of Darapladib on the Pharmacokinetics (PK) of Rosuvastatin as Well as Evaluating Safety and Tolerability in Healthy Volunteers
Condition: Atherosclerosis
MeSH terms: Atherosclerosis
Study type: Interventional
Phase: Phase 1

Summary: 
      The potential for a drug interaction between Darapladib and Rosuvastatin is felt to be low
      and it would be helpful to quantify this risk in man in order to guide prescribing
      physicians. The primary aims of this study are to estimate the potential effects of repeat
      doses of Darapladib on the PK of Rosuvastatin as well as evaluating safety and tolerability.
      Two part approaches are planned for this study. Part A of the study will examine the effects
      of repeat doses Darapladib on the PK of Rosuvastatin in healthy volunteers of Caucasian
      descent. Based on whether a significant increase in Rosuvastatin exposure is observed in
      Caucasians in Part A, a decision will be made regarding whether to proceed with a conditional
      Part B to examine this effect in healthy volunteers of Far-East Asian descent.

      In both parts, subjects will receive Rosuvastatin 10 milligrams (mg) once daily (QD) for 1
      day during the first treatment period (Treatment Period 1), followed by a 4 day PK sampling
      period/wash-out. Subjects will then receive darapladib 160 mg QD for the next 10 days with
      24-hour PK sampling on the last day (Day 14 of the study). Immediately following this, all
      subjects will then receive the combination of Darapladib 160 mg and Rosuvastatin 10 mg for 1
      day and continued Darapladib dosing of 160 mg QD for additional 3 days (Treatment Period 2)
      while blood samples are collected to assess Rosuvastatin PK. Plasma samples collected on Day
      15 will be analyzed for both Rosuvastatin and Darapladib concentrations.

      Subjects will be required to return to the unit approximately 10 to 14 days following the
      last dose of study medication for a clinic visit for assessments and then will return again
      at 35 ±7 days following the last dose for the final follow-up visit of the study. The
      duration of each subject's participation in the study from screening to follow-up will be
      approximately three months.

      Approximately 18 evaluable subjects will be enrolled in Part A and another 18 subjects will
      be enrolled in Part B (if conducted) to complete dosing and all assessments.
    


Intervention name(s): Rosuvastatin 10 mg; Darapladib 160 mg
Intervention type(s): Drug; Drug
Intervention description(s): Enteric coated tablet will be administered orally as a single dose once in Treatment Period 1 (Day 1) and Treatment Period 2 (Day 15).; Enteric coated tablet will be administered orally as once daily for 14 days in Treatment Period 2 only (Day 5 to Day 18).
Other intervention name(s): Crestor
Intervention MeSH terms: Rosuvastatin Calcium; Darapladib
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug interaction, rosuvastatin, healthy volunteer, Lp-PLA2, atherosclerosis, darapladib, pharmacokinetics.