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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Rucaparib; Drug: Rosuvastatin; Drug: Oral Contraceptives

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, 1076
    • PRA Magyarország Fázis I-es Klinikai Farmakológiai Vizsgálóhely FMC Dialízis Központ, II. em.
• Poland
  • Biała Podlaska, Poland, 21-500
    • Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
  • Józefów, Poland, 05-410
    • BioVirtus Centrum Medyczne
  • Kraków, Poland, 31-752
    • Ujastek Sp. z o.o. Centrum medyczne
  • Poznań, Poland, 60-693
    • Med Polonia Sp. z o.o.
  • Warszawa, Poland, 01-401
    • Zdrowie Kobiety Centrum Leczniczo-Rehabilitacyjne i Medycyny Pracy ATTIS Sp. z o.o., Zakład Onkologii Kobiecej
• Slovakia
  • Bratislava, Slovakia, 831 01
    • Summit Clinical Research s.r.o.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm A - rucaparib and oral rosuvastatin	Drug: Rucaparib; Rucaparib 600 mg BID commencing on Day 5 until Day 23.; Other Names: Rubraca; Drug: Rosuvastatin; Single dose of 20mg oral rosuvastatin on Day 1 and Day 19 only.; Other Names: Crestor
Other: Arm B - rucaparib and oral contraceptives	Drug: Rucaparib; Rucaparib 600 mg BID commencing on Day 5 until Day 23.; Other Names: Rubraca; Drug: Oral Contraceptives; Single dose of combined oral contraceptive (30 μg ethinylestradiol and 150 μg levonorgestrel) on Day 1 and Day 19 only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.	Maximum plasma concentration (Cmax)	Day 1 to Day 23
PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.	Area under the concentration-time curve (AUC) from time zero up to the last time point with a quantifiable concentration (AUC0-last)	Day 1 to Day 23
PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.	AUC up to time infinity, with extrapolation of the terminal phase (AUC0-inf)	Day 1 to Day 23

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events [Safety and Tolerability]		From Day 1 to last patient visit in Part II (approximately 2 years)
Incidence of clinical laboratory abnormalities [Safety and Tolerability]		From Day 1 to last patient visit in Part II (approximately 2 years)
Incidence of dose modifications [Safety and Tolerability]		From Day 1 to last patient visit in Part II (approximately 2 years)
PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.	Terminal half-life (t1/2)	Day 1 to Day 23
PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.	Time to occurrence of Cmax (tmax)	Day 1 to Day 23
PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.	Apparent total clearance of drug after oral administration (CL/F)	Day 1 to Day 23
PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.	Apparent volume of distribution during terminal phase (Vz/F)	Day 1 to Day 23
The following secondary PK parameter will be calculated for rucaparib.	Trough plasma concentration (Cmin)	Day 1 to Day 23

Collaborators and Investigators

• Sponsor: zr Pharma & GmbH

Publications and helpful links

General Publications

• Liao M, Jeziorski KG, Tomaszewska-Kiecana M, Lang I, Jasiowka M, Skarbova V, Centkowski P, Ramlau R, Gornas M, Lee J, Edwards S, Habeck J, Nash E, Grechko N, Xiao JJ. A phase 1, open-label, drug-drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2021 Nov;88(5):887-897. doi: 10.1007/s00280-021-04338-7. Epub 2021 Aug 9.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2019
• Primary Completion (Actual): December 6, 2019
• Study Completion (Actual): June 9, 2021

Study Registration Dates

• First Submitted: April 2, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 17, 2019

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: PARP Inhibitor; CO-338; Clovis; Clovis Oncology; Drug-drug Interaction; rucaparib
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Poly(ADP-ribose) Polymerase Inhibitors; Reproductive Control Agents; Contraceptive Agents, Female; Rosuvastatin Calcium; Contraceptive Agents; Contraceptives, Oral; Rucaparib
• Other Study ID Numbers: CO-338-095

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No