Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Olaparib

Rifampin

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Sequential treatments of olaparib alone followed by olaparib+rifampicin, with a washout period inbetween.

Blood sampling to measure olaparib, rifampicin and 4β-hydroxycholesterol

Pharmacokinetic sampling

Rifampicin (CYP inducer) 600mg taken once daily from Day 5 to Day 14 (Part A)

Rifampicin

Olaparib 300mg tablet taken on Days 1 and 14 (Part A). Part B dosing is 300mg olaparib bi-daily

Olaparib tablet dosing

Anitra Fielding

Luc Dirix

This is a 2-part study in patients with advanced solid tumours. Part A will investigate the effect of rifampicin on the PK parameters of olaparib in patients; Part B will allow patients continued access to olaparib after the PK phase and will provide additional safety data.

Study to Assess the Effect of Rifampicin (CYP Inducer) on Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours

A Non-randomised, Open-label, Sequential, Multicentre, Two-part, Phase I Study to Assess the Effect of Rifampicin, a CYP Inducer, on the Pharmacokinetics of Olaparib Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours

Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of maximum plasma olaparib concentration (Cmax). Olaparib doses are first without, then with rifampicin.

Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to infinity (AUC).

Olaparib doses are first without, then with rifampicin.

Rate and extent of absorption of olaparib following single 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. Olaparib doses are first without, then with rifampicin.

Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of time to reach maximum plasma concentration for olaparib (tmax). Olaparib doses are first without, then with rifampicin.

Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of olaparib area under the plasma concentration time curve from zero to the last measurable time point (AUC0-τ). Olaparib doses are first without, then with rifampicin.

Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of olaparib apparent clearance (CL/F). Olaparib doses are first without, then with rifampicin.

Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of olaparib apparent volume of distribution (Vz/F). Olaparib doses are first without, then with rifampicin.

Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of olaparib terminal half-life (t1/2). Olaparib doses are first without, then with rifampicin.

Rate and extent of absorption of rifampicin following multiple doses of rifampicin by assessment of plasma concentrations of rifampicin during rifampicin dosing period.

Demonstration of CYP induction by assessment of plasma concentrations of 4β-hydroxycholesterol during rifampicin dosing period.

Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.0

Assessment of standard 12 lead electrocardiograms (ECGs)

Assessment of standard vital signs (including blood pressure, pulse)

Assessment of laboratory parameters (clinical chemistry)

Assessment of laboratory parameters (haematology)

Assessment of laboratory parameters (urinalysis)

Spots Global Cancer Trial Database for oncology, cancer, tumour, anticancer drug, pharmacokinetics, olaparib, rifampicin, neoplasm, cyp p450 inducer