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出境医 / 临床实验 / Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer

Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer

Study Description
Brief Summary:
This is a 2-phase study in participants with advanced solid tumors. The first phase consists of Part A and Part B. Part A will investigate the effect of rifampin on the pharmacokinetics (PK) of pamiparib and Part B will investigate the effect of itraconazole in the PK of pamiparib. Phase 2 will allow participants continued access to pamiparib after the PK phase and will provide additional safety data.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: pamiparib (28 day cycles) Drug: pamiparib 60 mg Drug: pamiparib 20 mg Drug: itraconazole Drug: rifampin Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase 1, Open-label, Parallel-group, Fixed-sequence Study to Investigate the Effect of the CYP3A Inducer Rifampin and the CYP3A Inhibitor Itraconazole on the Pharmacokinetics of Pamiparib (BGB-290) in Cancer Patients
Actual Study Start Date : June 19, 2019
Actual Primary Completion Date : October 20, 2019
Estimated Study Completion Date : September 2, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Arm A (core phase) Drug: pamiparib 60 mg
single dose of 60 mg pamiparib orally in the fasted state (at least 8 hours predose)

Drug: rifampin
600 mg rifampin once a day in the fasted state (at least 2 hours predose)
Experimental: Arm B (core phase) Drug: pamiparib 20 mg
single dose of 20 mg pamiparib orally in the fasted state (at least 8 hours predose)

Drug: itraconazole
200 mg itraconazole once a day approximately 30 minutes after completing a meal
Experimental: Extension phase Drug: pamiparib (28 day cycles)
60 mg administered orally twice daily/ 28day cycles
Outcome Measures
Primary Outcome Measures :
  1. Area under the plasma concentration vs. time curve (AUC) [ Time Frame: up to 13 days ]
  2. Maximum plasma concentration (Cmax) [ Time Frame: up to 13 days ]
  3. Time to Cmax (Tmax) [ Time Frame: up to 13 days ]
  4. Terminal half-life (t1/2) [ Time Frame: up to 13 days ]
  5. Apparent plasma clearance (CL/F) [ Time Frame: up to 13 days ]
  6. Volume of distribution (Vz/F) [ Time Frame: up to 13 days ]

Secondary Outcome Measures :
  1. Number and severity of adverse effects [ Time Frame: Up to 6 months ]
  2. Number of laboratory abnormalities [ Time Frame: Up to 6 months ]
  3. 12-lead electrocardiogram (ECG) parameters [ Time Frame: Up to 6 months ]
  4. Physical examinations [ Time Frame: Up to 6 months ]
    Assessment of the participant's general appearance, skin, thorax/lungs, cardiovascular, and abdomen

  5. Blood pressure [ Time Frame: Up to 6 months ]
  6. Supine pulse rate [ Time Frame: Up to 6 months ]
  7. Respiratory rate [ Time Frame: Up to 6 months ]
  8. Body temperature [ Time Frame: Up to 6 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Age ≥ 18 years
  2. Histologically or cytologically confirmed advanced or metastatic solid tumors that are refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.
  3. Disease that is evaluable per RECIST Version 1.1 or Prostate Cancer Working Group-3 (PCWG-3)
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Appendix 2)
  5. Life expectancy ≥ 12 weeks
  6. Adequate hematologic and end-organ function

Key Exclusion Criteria:

  1. History of hypersensitivity to rifampin, any rifamycin or any of the components of the rifampin capsule (Part A).
  2. History of hypersensitivity to itraconazole or any of the components of the itraconazole capsule (Part B).

  3. Prior treatment with a PARP inhibitor at therapeutic doses is allowed, provided that such treatment was not the most recent therapy (PARP inhibitor must have been discontinued ≥ 3 months prior to the first dose of pamiparib):

    - Participants who experienced prior severe toxicity to PARP inhibitors that in the opinion of the investigator precludes further treatment with PARP inhibitors should be excluded

  4. Diagnosis of Myelodysplastic syndrome (MDS)
  5. Active infection requiring systemic treatment

  6. Any of the following cardiovascular criteria:

    1. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before Day 1 of pamiparib administration
    2. Symptomatic pulmonary embolism ≤ 28 days before Day 1 of pamiparib administration
    3. Any history of acute myocardial infarction ≤ 6 months before Day 1 of pamiparib administration

    4. Any history of heart failure meeting New York Heart Association Classification III or IV (Appendix 5) ≤ 6 months before Day 1 of pamiparib

      - Participants with congestive heart failure or history of heart failure should be excluded from Part B (itraconazole)

    5. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before Day 1 of pamiparib administration
    6. Any history of cerebral vascular accident ≤ 6 months before Day 1 of pamiparib administration

  7. Previous complete gastric resection or lap-band surgery, chronic diarrhea, active inflammatory gastrointestinal disease, known diverticular disease or any other disease-causing malabsorption syndrome

    - Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed

  8. Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena ≤ 6 months before Day 1 of pamiparib administration
  9. Use or anticipated need for food or drugs known to be strong or moderate CYP3A inhibitors or strong CYP3A inducers ≤ 14 days (or ≤ 5 half-lives if half-life is known) prior to Day 1 of pamiparib administration
  10. Known history of intolerance to the excipients of the pamiparib capsule
  11. Have known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations
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Georgia
Research Institute of Clinical Medicine
Tbilisi, Georgia, 0112
Moldova, Republic of
Republican Clinical Hospital, Oncology Department
Chisinau, Moldova, Republic of, 2025
Poland
Szpital LuxMed
Warsaw, Poland, 02-801
Slovakia
Summit Clinical Research, s.r.o.
Bratislava, Slovakia, 83101
Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Katie Wood BeiGene
Tracking Information
First Submitted Date  ICMJE June 18, 2019
First Posted Date  ICMJE June 21, 2019
Last Update Posted Date March 17, 2021
Actual Study Start Date  ICMJE June 19, 2019
Actual Primary Completion Date October 20, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2019)
  • Area under the plasma concentration vs. time curve (AUC) [ Time Frame: up to 13 days ]
  • Maximum plasma concentration (Cmax) [ Time Frame: up to 13 days ]
  • Time to Cmax (Tmax) [ Time Frame: up to 13 days ]
  • Terminal half-life (t1/2) [ Time Frame: up to 13 days ]
  • Apparent plasma clearance (CL/F) [ Time Frame: up to 13 days ]
  • Volume of distribution (Vz/F) [ Time Frame: up to 13 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2020)
  • Number and severity of adverse effects [ Time Frame: Up to 6 months ]
  • Number of laboratory abnormalities [ Time Frame: Up to 6 months ]
  • 12-lead electrocardiogram (ECG) parameters [ Time Frame: Up to 6 months ]
  • Physical examinations [ Time Frame: Up to 6 months ]
    Assessment of the participant's general appearance, skin, thorax/lungs, cardiovascular, and abdomen
  • Blood pressure [ Time Frame: Up to 6 months ]
  • Supine pulse rate [ Time Frame: Up to 6 months ]
  • Respiratory rate [ Time Frame: Up to 6 months ]
  • Body temperature [ Time Frame: Up to 6 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2019)
  • Number and severity of adverse effects [ Time Frame: Up to 6 months ]
  • Number of laboratory abnormalities [ Time Frame: Up to 6 months ]
  • 12-lead electrocardiogram (ECG) parameters [ Time Frame: Up to 6 months ]
  • Physical examinations [ Time Frame: Up to 6 months ]
    Assessment of the patient's general appearance, skin, thorax/lungs, cardiovascular, and abdomen
  • Blood pressure [ Time Frame: Up to 6 months ]
  • Supine pulse rate [ Time Frame: Up to 6 months ]
  • Respiratory rate [ Time Frame: Up to 6 months ]
  • Body temperature [ Time Frame: Up to 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer
Official Title  ICMJE A Phase 1, Open-label, Parallel-group, Fixed-sequence Study to Investigate the Effect of the CYP3A Inducer Rifampin and the CYP3A Inhibitor Itraconazole on the Pharmacokinetics of Pamiparib (BGB-290) in Cancer Patients
Brief Summary This is a 2-phase study in participants with advanced solid tumors. The first phase consists of Part A and Part B. Part A will investigate the effect of rifampin on the pharmacokinetics (PK) of pamiparib and Part B will investigate the effect of itraconazole in the PK of pamiparib. Phase 2 will allow participants continued access to pamiparib after the PK phase and will provide additional safety data.
Detailed Description Not Provided
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: Basic Science
Condition  ICMJE Solid Tumor
Intervention  ICMJE
  • Drug: pamiparib (28 day cycles)
    60 mg administered orally twice daily/ 28day cycles
  • Drug: pamiparib 60 mg
    single dose of 60 mg pamiparib orally in the fasted state (at least 8 hours predose)
  • Drug: pamiparib 20 mg
    single dose of 20 mg pamiparib orally in the fasted state (at least 8 hours predose)
  • Drug: itraconazole
    200 mg itraconazole once a day approximately 30 minutes after completing a meal
  • Drug: rifampin
    600 mg rifampin once a day in the fasted state (at least 2 hours predose)
Study Arms  ICMJE
  • Experimental: Arm A (core phase)
    Interventions:
    • Drug: pamiparib 60 mg
    • Drug: rifampin
  • Experimental: Arm B (core phase)
    Interventions:
    • Drug: pamiparib 20 mg
    • Drug: itraconazole
  • Experimental: Extension phase
    Intervention: Drug: pamiparib (28 day cycles)
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
Actual Enrollment  ICMJE
 (submitted: January 13, 2020) 		25
Original Estimated Enrollment  ICMJE
 (submitted: June 19, 2019) 		24
Estimated Study Completion Date  ICMJE September 2, 2021
Actual Primary Completion Date October 20, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Age ≥ 18 years
  2. Histologically or cytologically confirmed advanced or metastatic solid tumors that are refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.
  3. Disease that is evaluable per RECIST Version 1.1 or Prostate Cancer Working Group-3 (PCWG-3)
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Appendix 2)
  5. Life expectancy ≥ 12 weeks
  6. Adequate hematologic and end-organ function

Key Exclusion Criteria:

  1. History of hypersensitivity to rifampin, any rifamycin or any of the components of the rifampin capsule (Part A).
  2. History of hypersensitivity to itraconazole or any of the components of the itraconazole capsule (Part B).

  3. Prior treatment with a PARP inhibitor at therapeutic doses is allowed, provided that such treatment was not the most recent therapy (PARP inhibitor must have been discontinued ≥ 3 months prior to the first dose of pamiparib):

    - Participants who experienced prior severe toxicity to PARP inhibitors that in the opinion of the investigator precludes further treatment with PARP inhibitors should be excluded

  4. Diagnosis of Myelodysplastic syndrome (MDS)
  5. Active infection requiring systemic treatment

  6. Any of the following cardiovascular criteria:

    1. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before Day 1 of pamiparib administration
    2. Symptomatic pulmonary embolism ≤ 28 days before Day 1 of pamiparib administration
    3. Any history of acute myocardial infarction ≤ 6 months before Day 1 of pamiparib administration

    4. Any history of heart failure meeting New York Heart Association Classification III or IV (Appendix 5) ≤ 6 months before Day 1 of pamiparib

      - Participants with congestive heart failure or history of heart failure should be excluded from Part B (itraconazole)

    5. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before Day 1 of pamiparib administration
    6. Any history of cerebral vascular accident ≤ 6 months before Day 1 of pamiparib administration

  7. Previous complete gastric resection or lap-band surgery, chronic diarrhea, active inflammatory gastrointestinal disease, known diverticular disease or any other disease-causing malabsorption syndrome

    - Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed

  8. Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena ≤ 6 months before Day 1 of pamiparib administration
  9. Use or anticipated need for food or drugs known to be strong or moderate CYP3A inhibitors or strong CYP3A inducers ≤ 14 days (or ≤ 5 half-lives if half-life is known) prior to Day 1 of pamiparib administration
  10. Known history of intolerance to the excipients of the pamiparib capsule
  11. Have known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
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 Georgia,   Moldova, Republic of,   Poland,   Slovakia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03994211
Other Study ID Numbers  ICMJE BGB-290-105
2019-000112-28 ( EudraCT Number )
Has Data Monitoring Committee No
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
Plan to Share IPD: Yes
Responsible Party BeiGene
Study Sponsor  ICMJE BeiGene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Katie Wood BeiGene
PRS Account BeiGene
Verification Date March 2021

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

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