Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer
Condition: Solid Tumor
Intervention: pamiparib 60 mg; pamiparib 20 mg; itraconazole; rifampin; pamiparib
Intervention description: Single dose of 60 mg pamiparib orally on Days 1 and 10; Single dose of 20 mg pamiparib orally on days 1 and 7; 200 mg itraconazole once a day al Day 3 to day 8; 600 mg rifampin once a day from days 3 to 11; 60 mg pamiparib orally twice a day in 28-day cycles
Intervention MeSH terms: Itraconazole; Rifampin; Pamiparib
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The study was an open-label, parallel-group, fixed-sequence study in male and female cancer
      patients. The study consists of 2 phases: the Core Phase, which is divided into Part A and
      Part B, and the Extension Phase. Part A investigated the effect of CYP3A induction by
      rifampin on the single dose pharmacokinetics (PK) of pamiparib, and Part B investigated the
      effect of CYP3A inhibition by itraconazole on the single dose PK of pamiparib. Participants
      were offered participation in the Extension Phase, in which they received pamiparib until
      progression of disease, unacceptable toxicity, withdrawal of consent, or any other reason for
      discontinuation.
    

Eligibility 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

          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 poly (adenosine diphosphate [ADP]-ribose) polymerase (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 ≤ 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.