An Open-label, Non-randomised, Multicentre, Comparative, Phase I Study of the Pharmacokinetics, Safety and Tolerability of Olaparib Following a Single Oral 300 mg Dose to Patients With Advanced Solid Tumours and Normal Renal Function or Renal Impairment
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- CLR of Olaparib
Study Overview
Brief Summary
This is a 2-part study in patients with advanced solid tumours. Part A will investigate the PK of olaparib in patients with mild or moderate renal impairment compared to patients with normal renal function; Part B will allow eligible study patients continued access to olaparib after the PK phase and will provide additional safety data.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Normal renal function
Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation).
Intervention: Olaparib tablet dosing (Drug)
Mild renal impairment
Patients with calculated serum creatinine clearance 51-80 mL/min (using Cockcroft-Gault equation).
Intervention: Olaparib tablet dosing (Drug)
Moderate renal impairment
Patients with calculated serum creatinine clearance 31-50 mL/min (using Cockcroft-Gault equation).
Intervention: Olaparib tablet dosing (Drug)
Outcomes
Primary Outcomes
CLR of Olaparib
Time Frame: Part A: Day 1, 0-12 hours and 12-24 hours post-dose
Renal clearance of olaparib, calculated as the ratio of amount of drug excreted over 24 hours to AUC0-24
t1/2 of Olaparib
Time Frame: Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Terminal half-life of olaparib
Cmax of Olaparib
Time Frame: Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Maximum plasma drug concentration of olaparib
AUC of Olaparib
Time Frame: Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Area under plasma concentration-time curve from zero to infinity of olaparib
AUC0-t of Olaparib
Time Frame: Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Area under plasma concentration-time curve from zero to the last measurable time point of olaparib
Tmax of Olaparib
Time Frame: Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Time to reach maximum plasma concentration of olaparib
Vz/F of Olaparib
Time Frame: Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Apparent volume of distribution of olaparib
CL/F of Olaparib
Time Frame: Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Apparent plasma clearance of olaparib
Secondary Outcomes
No secondary outcomes reported