Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer
Study Details
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 |
|---|---|---|
|
Phase 1 |
Study Design
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
- Area under the plasma concentration vs. time curve (AUC) [up to 13 days]
- Maximum plasma concentration (Cmax) [up to 13 days]
- Time to Cmax (Tmax) [up to 13 days]
- Terminal half-life (t1/2) [up to 13 days]
- Apparent plasma clearance (CL/F) [up to 13 days]
- Volume of distribution (Vz/F) [up to 13 days]
Secondary Outcome Measures
- Number and severity of adverse effects [Up to 6 months]
- Number of laboratory abnormalities [Up to 6 months]
- 12-lead electrocardiogram (ECG) parameters [Up to 6 months]
- Physical examinations [Up to 6 months]
Assessment of the participant's general appearance, skin, thorax/lungs, cardiovascular, and abdomen
- Blood pressure [Up to 6 months]
- Supine pulse rate [Up to 6 months]
- Respiratory rate [Up to 6 months]
- Body temperature [Up to 6 months]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Age ≥ 18 years
-
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.
-
Disease that is evaluable per RECIST Version 1.1 or Prostate Cancer Working Group-3 (PCWG-3)
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Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Appendix 2)
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Life expectancy ≥ 12 weeks
-
Adequate hematologic and end-organ function
Key Exclusion Criteria:
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History of hypersensitivity to rifampin, any rifamycin or any of the components of the rifampin capsule (Part A).
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History of hypersensitivity to itraconazole or any of the components of the itraconazole capsule (Part B).
-
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
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Diagnosis of Myelodysplastic syndrome (MDS)
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Active infection requiring systemic treatment
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Any of the following cardiovascular criteria:
-
Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before Day 1 of pamiparib administration
-
Symptomatic pulmonary embolism ≤ 28 days before Day 1 of pamiparib administration
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Any history of acute myocardial infarction ≤ 6 months before Day 1 of pamiparib administration
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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)
-
Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before Day 1 of pamiparib administration
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Any history of cerebral vascular accident ≤ 6 months before Day 1 of pamiparib administration
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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
-
Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena ≤ 6 months before Day 1 of pamiparib administration
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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
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Known history of intolerance to the excipients of the pamiparib capsule
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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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Institute of Clinical Medicine | Tbilisi | Georgia | 0112 | |
| 2 | Republican Clinical Hospital, Oncology Department | Chisinau | Moldova, Republic of | 2025 | |
| 3 | Szpital LuxMed | Warsaw | Poland | 02-801 | |
| 4 | Summit Clinical Research, s.r.o. | Bratislava | Slovakia | 83101 |
Sponsors and Collaborators
- BeiGene
Investigators
- Study Director: Katie Wood, BeiGene
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGB-290-105
- 2019-000112-28