Investigate the Safety and Tolerability of Olaparib Tablet in Japanese Patients With Advanced Solid Malignancies

Phase 1

Completed

Brief Summary: The objective of this study will be to investigate the safety and tolerability of olaparib tablet when given orally to Japanese patients with advanced solid malignancies. In addition, the pharmacokinetic profile, MTD (if possible) and efficacy of olaparib will be investigated.

Recruitment & Eligibility

Inclusion Criteria

Subjects diagnosed with advanced solid malignancies who are refractory to standard therapies or for which no standard therapy exists.
Subjects who have overall good overall general condition.
Subjects who agree to hospitalisation from starting olaparib to multiple dose period at day 15.
Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status.
Subjects who have at least one lesion (measurable and/or non-measurable) that can be accurately assessed by CT/MRI at baseline and follow up visits

Exclusion Criteria

Subjects who received any previous treatment with a PARP (poly adenosine diphosphate-ribose polymerase) inhibitor, including olaparib.
Subjects receiving inhibitors of CYP3A4 (cytochrome P450 3A4).
Subjects with symptomatic uncontrolled brain metastases.
Subjects with myelodysplastic syndrome/acute myeloid leukaemia.
Subjects with a known hypersensitivity to olaparib or any of the excipients of the product.

Arm && Interventions

Group	Intervention	Description
olaparib tablet monotherapy	olaparib	olaparib tablet

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	From the start dose to 30 days after the last dose of study drug	An adverse event is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. This was recorded if it happend from the start dose to 30 days after the last of study drug.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities	From the start dose to 28 days after the first dose of study drug	Dose Limiting Toxicities were defined as study specific events that is determined to be possibly or probably related to olaparib (as determined by the investigator) and occurring during the first cycle of treatment (28 days after the first dose), irrespective of whether the toxicity resolved.
AUC at Steady State Following Multiple Dosing	Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose
AUC Following Single Dosing	Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose
Cmax Following Multiple Dosing	Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose
Cmax Following Single Dosing	Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose
Tmax Following Single Dosing	Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose
Tmax Following Multiple Dosing	Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose