To Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of Olaparib, and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation to Patients With Advanced Solid Tumours

Sponsor
AstraZeneca
Study ID
NCT01900028
Phase
PHASE1
Status
Completed

Conditions

  • Solid Tumours

Eligibility Criteria

Sex
ALL
Age
18 Years - 130 Years
Healthy Volunteers
Not accepted

Interventions

  • Pharmacokinetic sampling — PROCEDURE
    Blood samples taken pre and post dosing with olaparib+/- itraconazole
  • Olaparib tablet dosing — DRUG
    Olaparib tablets: Part A 100mg od, days 1 and 9 only. Part B 10x300mg doses over 5 days (300mg bd).
  • Itraconazole — DRUG
    Itraconazole 200mg od Part A days 5 to 11 only

Study Details

This is a 3-part study in patients with advanced solid tumours: Part A will assess the effect of itraconazole on the PK parameters of olaparib and will determine the effect of olaparib on the QT interval following single oral dosing; 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 after the PK and QT phases and will provide for additional safety data collection. A total of 48 patients are planned to be enrolled; at least 42 evaluable patients will be required to complete the study. Patients will participate as a single cohort in all parts of the study.

Key Dates

Start date
Oct 31, 2013
Status verified
Oct 2016
Primary completion
Apr 30, 2014
Completion
Sep 30, 2016

Study Design

Enrollment
85 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP

Arms

  • Experimental: Olaparib alone, olaparib+itraconozole
    Sequential treatments of olaparib alone followed by olaparib+itraconazole, with a washout period in between.

Primary Outcome Measure

Pharmacokinetics of olaparib by assessment of maximum plasma olaparib concentration (Cmax) [ Time Frame: Blood samples are collected on Day 1& Day 9 at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A. Part B:Day 5 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post dose ]

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