Drug-Drug Interaction Study of Rucaparib, Rosuvastatin and Oral Contraceptives

A Phase 1, Open-label, Drug-drug-interaction Study to Determine the Effect of Rucaparib on the Pharmacokinetics of Oral Rosuvastatin (Arm A) and Oral Contraceptives (Ethinylestradiol and Levonorgestrel) (Arm B) in Patients With Advanced Solid Tumors

This study will investigate the drug-drug interactions (DDIs) between rucaparib and oral rosuvastatin (Arm A), and between rucaparib and oral ethinylestradiol and levonorgestrel (Arm B), with rucaparib as a perpetrator.

This is a Phase 1, open-label, drug-drug-interaction (DDI) study in patients with advanced solid tumor. In Part I, the effects of rucaparib (600 mg twice daily [BID]) on the PK of oral rosuvastatin (Arm A) and the combined oral contraceptives (ethinylestradiol and levonorgestrel; Arm B) will be assessed.

Part I: patients will receive single oral doses of rosuvastatin or oral contraceptives (according to assigned arm) on Day 1 and Day 19. Continuous treatment with rucaparib at 600 mg BID will commence on Day 5 and continue until the end of Part I (Day 23).

Part II (optional): treatment with rucaparib in 28-day cycles may continue (at the discretion of the Investigator) until progression of disease, unacceptable toxicity, or other reason for discontinuation.

Inclusion Criteria (All patients):

• Willing to sign the ICF and to comply with the study restrictions
• Body mass index (BMI) 18.0 to 35.0 kg/m2
• Histologically or cytologically confirmed advanced solid tumor
• Patients who, in the opinion of the Investigator, could potentially benefit from treatment with rucaparib
• ECOG performance status less than or equal to 1
• Adequate organ function

Inclusion Criteria (Arm A):

- Male or female patients ≥ 18 years of age

Inclusion Criteria (Arm B):

- Female patients ≥ 18 years of age

Exclusion Criteria (All patients):

• Specific cancer treatments within 14 days prior to Day 1
• Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, acute coronary syndrome, cardiac angioplasty, stenting, or poorly controlled hypertension within the last 3 months prior to screening
• Pre-existing duodenal stent, recent or existing bowel obstruction
• Untreated or symptomatic central nervous system (CNS) metastases. Patients with treated asymptomatic CNS metastases are eligible
• Known HIV or AIDS-related illness, acute or history of chronic hepatitis B or C
• Female patients who are pregnant or breastfeeding
• Participation in another investigational drug trial within 30 days prior to Day 1 or exposure to more than 3 new investigational agents within 12 months prior to Day 1
• Presence of active infection requiring antibiotics
• Active second malignancy
• History of drug abuse (including alcohol)

Exclusion Criteria (Arm A):

• Current use of rosuvastatin or any other statin
• History of hypersensitivity to rosuvastatin
• Current, or history of, clinically significant myopathy

Exclusion Criteria (Arm B):

• Current use of any 1 of the contraceptive drugs or previous contraceptive implants or depot injections, which may still be clinically effective
• History of hypersensitivity to ethinylestradiol or levonorgestrel