Solid Tumor
Conditions
Brief 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.
Interventions
DRUGpamiparib 60 mg
Single dose of 60 mg pamiparib orally on Days 1 and 10
DRUGpamiparib 20 mg
Single dose of 20 mg pamiparib orally on days 1 and 7
DRUGitraconazole
200 mg itraconazole once a day al Day 3 to day 8
DRUGrifampin
600 mg rifampin once a day from days 3 to 11
DRUGpamiparib
60 mg pamiparib orally twice a day in 28-day cycles
Sponsors
BeiGene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part B | Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose |
| Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part B | Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose |
| Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part A | Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose |
| Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part A | Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose |
| Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part B | Part B: from Day -1 (admission) to Day 9 (discharge; ) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose |
| AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part A | Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose |
| AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part B | Part B: from Day -1 (admission) to Day 9 (discharge) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose |
| AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part A | Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose |
| AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part B | Part B: from Day -1 (admission) to Day 9 (discharge) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose |
| AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part A | Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, and 12 hours post-dose |
| AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part B | Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, and 12 hours post-dose |
| AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part A | Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, and 9 hours post-dose |
| AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part B | Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, and 9 hours post-dose |
| Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part A | Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose |
| Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part B | Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose |
| Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part A | Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose |
| Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part B | Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose |
| Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part A | Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | Up to approximately 26 months | — |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months) | TEAE is defined as any AE with an onset date on or after the date of first dose of study medication until the date of last study medication dose plus 30 days. Seriousness of the AE is determined by the investigator based on seriousness criteria. |
Countries
Georgia, Moldova, Poland, Slovakia
Participant flow
Recruitment details
This study consisted of a core phase and an extension phase. A total of 25 participants were enrolled in Poland, Moldova, Slovakia, and Georgia.
Pre-assignment details
The screening period consisted of Days -28 to -1.
Participants by arm
| Arm | Count |
|---|---|
| Core Phase: Arm A: Pamiparib + Rifampin Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose + 600 mg rifampin orally from Day 3 to Day 11 fasting at least 2 hours pre-dose | 12 |
| Core Phase: Arm B: Pamiparib + Itraconazole Participants received 20 mg pamiparib orally on Days 1 and 7 fasting at least 8 hours pre-dose + 200 mg itraconazole orally 30 minutes after meal Day 3 to Day 8 | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Core Phase | Adverse Event | 0 | 1 | 0 |
| Extension Phase | Adverse Event | 0 | 0 | 1 |
| Extension Phase | Physician Decision | 0 | 0 | 1 |
| Extension Phase | Progressive Disease | 0 | 0 | 20 |
| Extension Phase | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Core Phase: Arm B: Pamiparib + Itraconazole | Total | Core Phase: Arm A: Pamiparib + Rifampin |
|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 12.96 | 60.7 years STANDARD_DEVIATION 11.87 | 58.7 years STANDARD_DEVIATION 10.73 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 25 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 25 Participants | 12 Participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 | 0 / 24 |
| other Total, other adverse events | 5 / 12 | 6 / 13 | 18 / 24 |
| serious Total, serious adverse events | 0 / 12 | 1 / 13 | 2 / 24 |
Outcome results
Primary
Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part A
Time frame: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part A | 2.132 Liters/hour (L/h) |
| Part A: Pamiparib + Rifampin | Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part A | 3.232 Liters/hour (L/h) |
Primary
Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part B
Time frame: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part B | 1.987 Liters/hour (L/h) |
| Part A: Pamiparib + Rifampin | Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part B | 2.147 Liters/hour (L/h) |
Primary
Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part A
Time frame: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part A | 13.381 hours |
| Part A: Pamiparib + Rifampin | Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part A | 7.667 hours |
Primary
Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part B
Time frame: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part B | 9.290 hours |
| Part A: Pamiparib + Rifampin | Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part B | 11.179 hours |
Primary
Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part A
Time frame: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part A | 35.491 Liters |
| Part A: Pamiparib + Rifampin | Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part A | 37.712 Liters |
Primary
Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part B
Time frame: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part B | 34.697 Liters |
| Part A: Pamiparib + Rifampin | Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part B | 37.589 Liters |
Primary
AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part A
Time frame: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part A | 28868 hours*nanograms/milliLiter (h*ng/mL) |
| Part A: Pamiparib + Rifampin | AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part A | 18351 hours*nanograms/milliLiter (h*ng/mL) |
90% CI: [0.54, 0.7]
Primary
AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part B
Time frame: Part B: from Day -1 (admission) to Day 9 (discharge) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part B | 9163 hours*nanograms/milliLiter (h*ng/mL) |
| Part A: Pamiparib + Rifampin | AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part B | 8894 hours*nanograms/milliLiter (h*ng/mL) |
90% CI: [0.91, 1.09]
Primary
AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part A
Time frame: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, and 12 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part A | 14642.90 hr*ng/mL |
| Part A: Pamiparib + Rifampin | AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part A | 12262.61 hr*ng/mL |
Primary
AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part B
Time frame: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, and 12 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part B | 5097.06 hr*ng/mL |
| Part A: Pamiparib + Rifampin | AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part B | 4647.47 hr*ng/mL |
Primary
AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part A
Time frame: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, and 9 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part A | 11821.06 hr*ng/mL |
| Part A: Pamiparib + Rifampin | AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part A | 10515.14 hr*ng/mL |
Primary
AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part B
Time frame: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, and 9 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part B | 4267.86 hr*ng/mL |
| Part A: Pamiparib + Rifampin | AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part B | 3812.39 hr*ng/mL |
Primary
AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part A
Time frame: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part A | 28142 hr*ng/mL |
| Part A: Pamiparib + Rifampin | AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part A | 18563 hr*ng/mL |
90% CI: [0.48, 0.69]
Primary
AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part B
Time frame: Part B: from Day -1 (admission) to Day 9 (discharge) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part B | 10072 hr*ng/mL |
| Part A: Pamiparib + Rifampin | AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part B | 9353 hr*ng/mL |
90% CI: [0.9, 1.09]
Primary
Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part A
Time frame: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Population: The pharmacokinetic (PK) population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an adverse event (AE) of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part A | 1970 ng/mL |
| Part A: Pamiparib + Rifampin | Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part A | 1820 ng/mL |
90% CI: [0.83, 1.06]
Primary
Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part B
Time frame: Part B: from Day -1 (admission) to Day 9 (discharge; ) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Population: The pharmacokinetic (PK) population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an adverse event (AE) of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part B | 730.5 ng/mL |
| Part A: Pamiparib + Rifampin | Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part B | 752.5 ng/mL |
90% CI: [0.95, 1.15]
Primary
Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part A
Time frame: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part A | 2.000 hours |
| Part A: Pamiparib + Rifampin | Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part A | 2.000 hours |
Primary
Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part B
Time frame: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Population: The PK population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 x median tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pamiparib | Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part B | 2.000 hours |
| Part A: Pamiparib + Rifampin | Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part B | 1.000 hours |
Secondary
Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations
Time frame: Up to approximately 26 months
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Pamiparib | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | Laboratory Assessments | 0 Number of participants |
| Part A: Pamiparib | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | Vital Signs | 0 Number of participants |
| Part A: Pamiparib | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | Physical Examinations | 0 Number of participants |
| Part A: Pamiparib | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | ECG Parameters | 0 Number of participants |
| Part A: Pamiparib + Rifampin | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | ECG Parameters | 0 Number of participants |
| Part A: Pamiparib + Rifampin | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | Laboratory Assessments | 0 Number of participants |
| Part A: Pamiparib + Rifampin | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | Physical Examinations | 0 Number of participants |
| Part A: Pamiparib + Rifampin | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | Vital Signs | 0 Number of participants |
| Extension Phase | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | Physical Examinations | 0 Number of participants |
| Extension Phase | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | ECG Parameters | 0 Number of participants |
| Extension Phase | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | Vital Signs | 0 Number of participants |
| Extension Phase | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations | Laboratory Assessments | 0 Number of participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAE is defined as any AE with an onset date on or after the date of first dose of study medication until the date of last study medication dose plus 30 days. Seriousness of the AE is determined by the investigator based on seriousness criteria.
Time frame: From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Population: Safety Analysis Set includes all participants who received at least 1 dose of pamiparib
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Pamiparib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | All TEAEs | 5 Number of participants |
| Part A: Pamiparib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Serious TEAEs | 0 Number of participants |
| Part A: Pamiparib + Rifampin | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | All TEAEs | 6 Number of participants |
| Part A: Pamiparib + Rifampin | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Serious TEAEs | 1 Number of participants |
| Extension Phase | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Serious TEAEs | 2 Number of participants |
| Extension Phase | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | All TEAEs | 18 Number of participants |