Antineoplastic Agents

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Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Olaparib tablets after high-fat breakfast

Olaparib dosing (2X 150mg tablets) following allocated meal

Olaparib tablets

Blood samples taken pre and post dosing with 2x 150 mg olaparib tablet

Pharmacokinetic sampling

2x 150 mg olaparib tablet formulation taken in fasted state. 5-14 days washout period

Dietary Fasted

2x 150 mg olaparib tablet formulation taken 30 minutes after allocated meal. 5-14 days washout period.

Dietary High Fat

Anitra Fielding

Ruth Plummer, Prof

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.

To Determine the Effect of Food on the Pharmacokinetics of Olaparib and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours

A Randomised, Open-label, Three-part, Phase I Study to Determine the Effect of Food on the Pharmacokinetics of Olaparib and to Provide Data on the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

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)

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)

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.

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)

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)

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)

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)

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).

The QT interval uncorrected and corrected for heart rate (QTc) following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation.

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),

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.

AstraZeneca

Olaparib capsules after standard breakfast

Olaparib capsules after high fat breakfast

400mg olaparib capsule formulation taken 30 minutes after allocated meal. 5-14 days between arms.

Allocated breakfast prior to dosing with 400mg olaparib capsules

Dietary standard

Christian Rolfo

Wendy Bannister

This is a 2 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 3 different breakfasts (high calorie, regular and none). In Part B Patients can take olaparib capsules daily and study assessments will be recorded for 6 months (minimum). Treatment can continue for as long as the patient is benefitting. Throughout the study patients will be monitored for any side effects.

D081AC00001 Food Interaction With Olaparib Capsule in Patients With Solid Tumours

A Two-part, Randomised, Open-label, Multicentre, Phase I Study to Determine the Effect of Food on the Pharmacokinetics of Olaparib Following Single 400 mg Doses of the Capsule Formulation in Patients With Advanced Solid Tumours.

Rate and extent of absorption of olaparib following single-dose olaparib by assessment of maximum plasma olaparib concentration (Cmax) and time to reach maximum plasma concentration (tmax)

Rate and extent of absorption of olaparib following single-dose olaparib by assessment of area under the plasma concentration time curve from zero to the last measurable time point (AUC0-t)

Rate and extent of absorption of olaparib following single-dose olaparib by assessment of area under the plasma concentration time curve from zero to infinity (AUC)

Rate and extent of absorption of olaparib following single-dose olaparib by assessment of apparent clearance following oral administration (CL/F), apparent volume of distribution (Vz/F), terminal rate constant (λz), and terminal half-life (t½)

Assessment of adverse events (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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
To Determine the Effect of Food on the Pharmacokinetics of Olaparib and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours	NCT01921140	Solid Tumours	Olaparib tablet... Pharmacokinetic... Dietary Fasted Dietary High Fa...	18 Years - 130 Years	AstraZeneca
To Determine the Effect of Food on the Pharmacokinetics of Olaparib and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours	NCT01921140	Solid Tumours	Olaparib tablet... Pharmacokinetic... Dietary Fasted Dietary High Fa...	18 Years - 130 Years	AstraZeneca
To Determine the Effect of Food on the Pharmacokinetics of Olaparib and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours	NCT01921140	Solid Tumours	Olaparib tablet... Pharmacokinetic... Dietary Fasted Dietary High Fa...	18 Years - 130 Years	AstraZeneca
D081AC00001 Food Interaction With Olaparib Capsule in Patients With Solid Tumours	NCT01851265	Solid Tumours	Olaparib Dietary Fasted Dietary standar... Dietary High Fa...	18 Years - 130 Years	AstraZeneca
D081AC00001 Food Interaction With Olaparib Capsule in Patients With Solid Tumours	NCT01851265	Solid Tumours	Olaparib Dietary Fasted Dietary standar... Dietary High Fa...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for dietary fasted