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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03954366
• Other study ID #: CO-338-095
• Status: Completed
• Phase: Phase 1
• Start date: April 25, 2019
• Est. completion date: June 9, 2021

Study information

• Verified date: June 2023
• Source: zr Pharma & GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 9, 2021
• Est. primary completion date: December 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Rucaparib
Rucaparib 600 mg BID commencing on Day 5 until Day 23.
• Rosuvastatin
Single dose of 20mg oral rosuvastatin on Day 1 and Day 19 only.
• Oral Contraceptives
Single dose of combined oral contraceptive (30 µg ethinylestradiol and 150 µg levonorgestrel) on Day 1 and Day 19 only.

Locations

Country	Name	City	State
Hungary	PRA Magyarország Fázis I-es Klinikai Farmakológiai Vizsgálóhely FMC Dialízis Központ, II. em.	Budapest
Poland	Wojewódzki Szpital Specjalistyczny w Bialej Podlaskiej	Biala Podlaska
Poland	BioVirtus Centrum Medyczne	Józefów
Poland	Ujastek Sp. z o.o. Centrum medyczne	Kraków
Poland	Med Polonia Sp. z o.o.	Poznan
Poland	Zdrowie Kobiety Centrum Leczniczo-Rehabilitacyjne i Medycyny Pracy ATTIS Sp. z o.o., Zaklad Onkologii Kobiecej	Warszawa
Slovakia	Summit Clinical Research s.r.o.	Bratislava

Sponsors (1)

Lead Sponsor	Collaborator
zr Pharma & GmbH

Countries where clinical trial is conducted

Hungary,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.	Maximum plasma concentration (Cmax)	Day 1 to Day 23
Primary	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
Primary	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	PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.	Terminal half-life (t1/2)	Day 1 to Day 23
Secondary	PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.	Time to occurrence of Cmax (tmax)	Day 1 to Day 23
Secondary	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
Secondary	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
Secondary	The following secondary PK parameter will be calculated for rucaparib.	Trough plasma concentration (Cmin)	Day 1 to Day 23
Secondary	Incidence of Adverse Events [Safety and Tolerability]		From Day 1 to last patient visit in Part II (approximately 2 years)
Secondary	Incidence of clinical laboratory abnormalities [Safety and Tolerability]		From Day 1 to last patient visit in Part II (approximately 2 years)
Secondary	Incidence of dose modifications [Safety and Tolerability]		From Day 1 to last patient visit in Part II (approximately 2 years)