D081AC00001 Food Interaction With Olaparib Capsule in Patients With Solid Tumours

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Solid Tumours

Intervention / Treatment
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* Drug: Olaparib
* Other: Dietary Fasted
* Other: Dietary standard
* Other: Dietary High Fat


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oncology, cancer, tumour, neoplasm, anticancer drug, food effect, area under the curve, pharmacokinetics, olaparib, solid tumour, metabolites, drug availability