AZ: D0816C00007 Ph 1 - Effect of Inhibitor in Advanced Solid Tumours
Research type
Research Study
Full title
A Non-randomised, Open-label, Sequential, Three-part, Phase I Study to Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of Olaparib Following Oral Dosing of a Tablet Formulation, and to Provide Data on the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation to Patients with Advanced Solid Tumours
IRAS ID
131426
Contact name
Elizabeth Ruth Plummer
Contact email
Sponsor organisation
AstraZeneca AB
Eudract number
2013-001892-18
ISRCTN Number
N/A
Research summary
This is a three party study for patients over 18 years old with advanced solid tumours, whose tumours have failed to respond to standard treatments. Patients will receive the study drug Olaparib in tablet form which will be taken orally. Itraconazole is a drug commonly used in hospitals and clinics to treat fungal infections and may alter the way that Olaparib is broken down and excreted by the body by inhibiting CYP3A4, a liver enzyme.
Part A will assess the effect of itraconazole on the breakdown and excretion (pharmacokinetics) of Olaparib and also the effect of Olaparib on the electrical activity of the heart (QT interval) following a single oral dose.
Part A consists of two treatment periods; a single oral dose of Olaparib alone and a single oral dose of Olaparib given after the fifth dose of Itraconazole during visit five. Patients will then take a further two doses of Itraconazole (a total of seven doses). Part A will require patients to attend seven visits over an approximate two week period which will include five overnight stays. Patient will be required to fast three times during that period for the two days preceding the first Olaparib dose and on day-1 preceding the second Olaparib dose.
Part B will investigate the effect of study on the heart's electrical activity (QT interval) following multiple oral doses of Olaparib. In part B patient will be required to take 10 doses of Olaparib over a period of five days. Patients will attend two visits, the first two days before starting the Olaparib five day treatment period and the second visit on day four of the five day treatment period. Both visits require an overnight stay. Patient will be required to fast on each of these overnight stays. The results of parts A and B will allow us to advise if the Olaparib dose needs reducing when patients are taking other medicines such as Itrconazole, which may alter the breakdown and excretion of Olaparib and if, or how often, the heart's electrical activity needs to be monitored for patients taking Olaparib.
Many ECGs (tracings of the heart's electrical activity) and blood samples to measure the amount of Olaparib in the blood will be taken during parts A and B. Some of the blood samples are for assessing safety/tolerability. The urine samples are for pregnancy and laboratory safety testing.
Part C will allow patients continued access to Olaparib after the PK and QT phases and will provide for additional safety data collection. Patients may receive therapeutic benefit during continuous dosing with Olaparib but this is not guaranteed. Patients will have weekly safety visits to the clinic for the first month and then monthly visits thereafter for approximately 12 months. If the investigator and patient agree that the patient is receiving benefit from treatment with Olaparib with 12 months treatment, the patient may continue treatment with Olaparib. A total of 48 patients are planned to be enrolled.
REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
13/NE/0189
Date of REC Opinion
2 Jul 2013
REC opinion
Favourable Opinion