This is a 3 part study for patients with solid tumours. The purpose of Part A is to measure the amount of olaparib or its breakdown products in the bloodstream for up to 72 hours after eating and the effect of olaparib on QT interval following a single oral dose of olaparib tablets. Part B will determine the effect of olaparib on the QT interval following multiple oral dosing. Part C will allow patients continued access to olaparib tablets and will provide additional safety data collection.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
60
Olaparib dosing (2X 150mg tablets) following allocated meal
Blood samples taken pre and post dosing with 2x 150 mg olaparib tablet
2x 150 mg olaparib tablet formulation taken in fasted state. 5-14 days washout period
2x 150 mg olaparib tablet formulation taken 30 minutes after allocated meal. 5-14 days washout period.
Research Site
Brussels, Belgium
Research Site
Leuven, Belgium
Research Site
Liège, Belgium
Research Site
Herlev, Denmark
Research Site
København Ø, Denmark
Research Site
Maastricht, Netherlands
Research Site
Nijmegen, Netherlands
Research Site
Utrecht, Netherlands
Research Site
London, United Kingdom
Research Site
Manchester, United Kingdom
...and 2 more locations
Pharmacokinetics of olaparib: area under the plasma-time curve from zero to infinity (AUC)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to infinity (AUC)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib:maximum olaparib concentration (Cmax)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of maximum plasma olaparib concentration (Cmax)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib: area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately estimable (AUC0-t)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to the last measurable time point (AUC0-t), if AUC is not adequately estimable.
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib time to reach maximum plasma concentration for olaparib (tmax)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of time to reach maximum plasma concentration for olaparib (tmax)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib olaparib apparent clearance (CL/F)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib apparent clearance (CL/F)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib:apparent volume of distribution (Vz/F)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib apparent volume of distribution (Vz/F)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib :terminal rate constant (λz)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of terminal rate constant (λz)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib:terminal half-life (t1/2).
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib terminal half-life (t1/2).
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Assessment of electrocardiogram (ECG) intervals (including QT and QTc interval)
The QT interval uncorrected and corrected for heart rate (QTc) following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation.
Time frame: Digital ECG's will be recorded at Day-1, Day 1 of both treatment periods in Part A at: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post olaparib dose. Part B Day -1 & Day 5: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
To assess the safety and tolerability of olaparib following oral dosing
Adverse events (AEs) will be collected from the time of signed informed consent throughout the treatment period in Part A and Part B up to and including the 30-day follow-up period. In Part C, AEs will be collected until 12 months after the last patient entered Part C, and including the 30 day follow-up period for any patients who discontinue. Assessment of AEs, graded by CTCAE (v4.03),
Time frame: Part A&B: Adverse events (AEs) will be collected from the time of signed informed consent up to and including the 30-day follow-up period. In Part C, AEs will be collected for 12 months
To assess safety and tolerability of oral olaparib dosing
Assessment of AEs, graded by CTCAE (v4.0), physical examination, vital signs (including BP and pulse), standard 12-lead ECG and evaluation of laboratory parameters (clinical chemistry, haematology, and urinalysis). Assessment of physical examination, vital signs, ECG and evaluation of laboratory parameters will occur at screening, on the day before dosing in each treatment period and 30 days after last dose in Parts A and B. In Part C, all except ECG will be assessed weekly for a 28-day period followed by every 4 weeks up to 12 months after the last patient enters Part C and at treatment discontinuation. All will be assessed 30 days after last dose.
Time frame: Laboratory and vital sign assessments will be carried out at baseline and then at every scheduled visit until 30 days post last dose
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