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.

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumours
• Intervention / Treatment: Drug: Olaparib; Other: Dietary Fasted; Other: Dietary standard; Other: Dietary High Fat

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Wilrijk, Belgium, 2610
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Research Site
  • Maastricht, Netherlands, 6202 AZ
    • Research Site
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged ≥18 years, male and female
• Able to eat a high-fat breakfast within a 30-minute period, as provided by the study site
• Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy and for which no suitable effective standard therapy exists
• ECOG performance status ≤2
• Normal organ and bone marrow function measured within 28 days prior to administration of IP as defined in protocol

Exclusion Criteria:

• Participation in another clinical study with an IP during the last 14 days (or a longer period depending on the defined characteristics of the agents used)
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment (or a longer period depending on the defined characteristics of the agents used).
• Toxicities (≥CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia
• Patients unable to fast for up to 14 hours or who have type I or type II diabetes
• Patients who have gastric, gastro-oesophageal or oesophageal cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Fasted; Olaparib capsules following no breakfast	Drug: Olaparib; 400mg olaparib capsule formulation taken 30 minutes after allocated meal. 5-14 days between arms.; Other: Dietary Fasted; Allocated breakfast prior to dosing with 400mg olaparib capsules
Other: Standard meal; Olaparib capsules after standard breakfast	Drug: Olaparib; 400mg olaparib capsule formulation taken 30 minutes after allocated meal. 5-14 days between arms.; Other: Dietary standard; Allocated breakfast prior to dosing with 400mg olaparib capsules
Other: High Fat; Olaparib capsules after high fat breakfast	Drug: Olaparib; 400mg olaparib capsule formulation taken 30 minutes after allocated meal. 5-14 days between arms.; Other: Dietary High Fat; Allocated breakfast prior to dosing with 400mg olaparib capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of Olaparib (Cmax and tmax)	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)	Blood samples will be collected in each of the 3 treatment periods in Part A at these time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72hours post dose
Pharmacokinetics of Olaparib (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 the last measurable time point (AUC0-t)	Blood samples will be collected in each of the 3 treatment periods in Part A at these time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72hours post dose.
Pharmacokinetics of Olaparib (AUC)	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)	Blood samples will be collected in each of the 3 treatment periods in Part A at these time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72hours post dose
Pharmacokinetics of Olaparib Pharmacokinetics of Olaparib (CL/F, Vz/F, λz and t½)	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)	Blood samples will be collected in each of the 3 treatment periods in Part A at these time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72hours post dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety monitoring of Olaparib	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.	AEs will be collected from signed informed consent up to 30-day post last dose in Part A. For patients in Part B, AE's will be collected until the final patient has completed 6 months in Part B, including 30 day follow up for those who discontinue

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Anitra Fielding, AstraZeneca Senior Research Physician; Principal Investigator: Christian Rolfo, UZ Antwerpen; Study Chair: Wendy Bannister, AstraZeneca Study Statistician

Publications and helpful links

Helpful Links

• D081AC00001_CSR_Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2013
• Primary Completion (Actual): October 18, 2013
• Study Completion (Actual): June 6, 2017

Study Registration Dates

• First Submitted: May 8, 2013
• First Submitted That Met QC Criteria: May 8, 2013
• First Posted (Estimate): May 10, 2013

Study Record Updates

• Last Update Posted (Actual): August 28, 2017
• Last Update Submitted That Met QC Criteria: August 25, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: oncology, cancer, tumour, neoplasm, anticancer drug, food effect, area under the curve, pharmacokinetics, olaparib, solid tumour, metabolites, drug availability
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: D081AC00001; 2013-001255-13 (EudraCT Number)