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出境医 / 临床实验 / Drug-Drug Interaction Study of Rucaparib, Rosuvastatin and Oral Contraceptives

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

Study Description
Brief 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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Rucaparib Drug: Rosuvastatin Drug: Oral Contraceptives Phase 1

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : May 8, 2019
Actual Primary Completion Date : December 6, 2019
Estimated Study Completion Date : March 2021
Arms and Interventions
Arm Intervention/treatment
Arm A - rucaparib and oral rosuvastatin Drug: Rucaparib
Rucaparib 600 mg BID commencing on Day 5 until Day 23.
Other Name: Rubraca

Drug: Rosuvastatin
Single dose of 20mg oral rosuvastatin on Day 1 and Day 19 only.
Other Name: Crestor

Arm B - rucaparib and oral contraceptives Drug: Rucaparib
Rucaparib 600 mg BID commencing on Day 5 until Day 23.
Other Name: Rubraca

Drug: Oral Contraceptives
Single dose of combined oral contraceptive (30 μg ethinylestradiol and 150 μg levonorgestrel) on Day 1 and Day 19 only.

Outcome Measures
Primary Outcome Measures :
  1. PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Maximum plasma concentration (Cmax)

  2. PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Area under the concentration-time curve (AUC) from time zero up to the last time point with a quantifiable concentration (AUC0-last)

  3. PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    AUC up to time infinity, with extrapolation of the terminal phase (AUC0-inf)


Secondary Outcome Measures :
  1. PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Terminal half-life (t1/2)

  2. PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Time to occurrence of Cmax (tmax)

  3. PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Apparent total clearance of drug after oral administration (CL/F)

  4. PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Apparent volume of distribution during terminal phase (Vz/F)

  5. The following secondary PK parameter will be calculated for rucaparib. [ Time Frame: Day 1 to Day 23 ]
    Trough plasma concentration (Cmin)

  6. Incidence of Adverse Events [Safety and Tolerability] [ Time Frame: From Day 1 to last patient visit in Part II (approximately 2 years) ]
  7. Incidence of clinical laboratory abnormalities [Safety and Tolerability] [ Time Frame: From Day 1 to last patient visit in Part II (approximately 2 years) ]
  8. Incidence of dose modifications [Safety and Tolerability] [ Time Frame: From Day 1 to last patient visit in Part II (approximately 2 years) ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Both male and female patients are eligible for Arm A. Female patients only are eligible for Arm B.
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Locations
Layout table for location information
Hungary
PRA Magyarország Fázis I-es Klinikai Farmakológiai Vizsgálóhely FMC Dialízis Központ, II. em.
Budapest, Hungary, 1076
Poland
Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
Biała Podlaska, Poland, 21-500
BioVirtus Centrum Medyczne
Józefów, Poland, 05-410
Ujastek Sp. z o.o. Centrum medyczne
Kraków, Poland, 31-752
Med Polonia Sp. z o.o.
Poznań, Poland, 60-693
Zdrowie Kobiety Centrum Leczniczo-Rehabilitacyjne i Medycyny Pracy ATTIS Sp. z o.o., Zakład Onkologii Kobiecej
Warszawa, Poland, 01-401
Slovakia
Summit Clinical Research s.r.o.
Bratislava, Slovakia, 831 01
Sponsors and Collaborators
Clovis Oncology, Inc.
Tracking Information
First Submitted Date  ICMJE April 2, 2019
First Posted Date  ICMJE May 17, 2019
Last Update Posted Date February 10, 2021
Actual Study Start Date  ICMJE May 8, 2019
Actual Primary Completion Date December 6, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Maximum plasma concentration (Cmax)
  • PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Area under the concentration-time curve (AUC) from time zero up to the last time point with a quantifiable concentration (AUC0-last)
  • PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    AUC up to time infinity, with extrapolation of the terminal phase (AUC0-inf)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Terminal half-life (t1/2)
  • PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Time to occurrence of Cmax (tmax)
  • PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Apparent total clearance of drug after oral administration (CL/F)
  • PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. [ Time Frame: Day 1 to Day 23 ]
    Apparent volume of distribution during terminal phase (Vz/F)
  • The following secondary PK parameter will be calculated for rucaparib. [ Time Frame: Day 1 to Day 23 ]
    Trough plasma concentration (Cmin)
  • Incidence of Adverse Events [Safety and Tolerability] [ Time Frame: From Day 1 to last patient visit in Part II (approximately 2 years) ]
  • Incidence of clinical laboratory abnormalities [Safety and Tolerability] [ Time Frame: From Day 1 to last patient visit in Part II (approximately 2 years) ]
  • Incidence of dose modifications [Safety and Tolerability] [ Time Frame: From Day 1 to last patient visit in Part II (approximately 2 years) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Drug-Drug Interaction Study of Rucaparib, Rosuvastatin and Oral Contraceptives
Official Title  ICMJE 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
Brief 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: Rucaparib
    Rucaparib 600 mg BID commencing on Day 5 until Day 23.
    Other Name: Rubraca
  • Drug: Rosuvastatin
    Single dose of 20mg oral rosuvastatin on Day 1 and Day 19 only.
    Other Name: Crestor
  • Drug: Oral Contraceptives
    Single dose of combined oral contraceptive (30 μg ethinylestradiol and 150 μg levonorgestrel) on Day 1 and Day 19 only.
Study Arms  ICMJE
  • Arm A - rucaparib and oral rosuvastatin
    Interventions:
    • Drug: Rucaparib
    • Drug: Rosuvastatin
  • Arm B - rucaparib and oral contraceptives
    Interventions:
    • Drug: Rucaparib
    • Drug: Oral Contraceptives
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 15, 2019)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2021
Actual Primary Completion Date December 6, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Gender Eligibility Description: Both male and female patients are eligible for Arm A. Female patients only are eligible for Arm B.
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Hungary,   Poland,   Slovakia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03954366
Other Study ID Numbers  ICMJE CO-338-095
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Clovis Oncology, Inc.
Study Sponsor  ICMJE Clovis Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Clovis Oncology, Inc.
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP