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

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ClinicalTrials.gov Identifier: NCT03994211
Recruitment Status : Recruiting
First Posted : June 21, 2019
Last Update Posted : November 1, 2019
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
This is a 2-phase study in patients with advanced solid tumors. The first phase consists of Part A and Part B. Part A will investigate the effect of rifampin on the PK of pamiparib and Part B will investigate the effect of itraconazole in the PK of pamiparib. Phase 2 will allow patients 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 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
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine


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




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 patient'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 ]


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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

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 PCWG-3
  4. ECOG performance status ≤ 1 (Appendix 2)
  5. Life expectancy ≥ 12 weeks
  6. Adequate hematologic and end-organ function

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):

    - Patients 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

      - Patients 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03994211


Contacts
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Contact: BeiGene +1-877-828-5568 clinicaltrials@beigene.com

Locations
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Georgia
Research Institute of Clinical Medicine Recruiting
Tbilisi, Georgia, 0112
Moldova, Republic of
Republican Clinical Hospital, Oncology Department Recruiting
Chisinau, Moldova, Republic of, 2025
Poland
Szpital LuxMed Recruiting
Warsaw, Poland, 02-801
Slovakia
Summit Clinical Research, s.r.o. Recruiting
Bratislava, Slovakia, 83101
Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Heinrich Farin, MD BeiGene

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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03994211     History of Changes
Other Study ID Numbers: BGB-290-105
2019-000112-28 ( EudraCT Number )
First Posted: June 21, 2019    Key Record Dates
Last Update Posted: November 1, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Itraconazole
Hydroxyitraconazole
Rifampin
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers