Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Itraconazole

Pamiparib

Rifampin

Hydroxyitraconazole

Cytochrome P-450 CYP3A Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Poly(ADP-ribose) Polymerase Inhibitors

60 mg pamiparib administered orally on Days 1 and 10 fasting 8 hours pre-dose 600 mg rifampin once a day from days 3 to 11 in the fasted state (at least 2 hours predose)

Single dose of 20 mg pamiparib orally in the fasted state (at least 8 hours predose) on days 1 and 7 200 mg itraconazole once a day approximately 30 minutes after completing a meal Day 3 to day 8

60 mg pamiparib orally twice a day in 28-day cycles until progression of disease

Single dose of 60 mg pamiparib orally on Days 1 and 10

pamiparib 60 mg

Single dose of 20 mg pamiparib orally on days 1 and 7

pamiparib 20 mg

200 mg itraconazole once a day al Day 3 to day 8

itraconazole

600 mg rifampin once a day from days 3 to 11

rifampin

60 mg pamiparib orally twice a day in 28-day cycles

pamiparib

Study Director

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.

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

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

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.

BeiGene

Participants received 60 milligrams (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

Core Phase: Arm A: Pamiparib + Rifampin

Participants received 20 mg pamiparib orally from Days 1 and 7 fasting at least 8 hours pre-dose + 200 mg itraconazole orally 30 minutes after meal Day 3 to Day 8

Core Phase: Arm B: Pamiparib + Itraconazole

Participants received 60 mg pamiparib orally twice a day in 28-day cycles until progression of disease, unacceptable toxicity, withdrawal of consent, or any other reason for discontinuation

Extension Phase

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

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

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The safety population included all participants who received at least 1 dose of pamiparib

Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose

Part A: Pamiparib

Participants received 60 mg pamiparib Days 1 and 10 + 600 mg rifampin orally from Day 3 to Day 11 fasting at least 2 hours pre-dose

Part A: Pamiparib + Rifampin

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.

Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part A

Participants received 20 mg pamiparib orally from Days 1 and 7 fasting at least 8 hours pre-dose

Part B: Pamiparib

Participants received pamiparib 20 mg fasting on Days 1 and 7 + 200 mg itraconazole orally 30 minutes after meal Day 3 to Day 8

Part B: Pamiparib + Itraconazole

Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part B

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.

AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part A

AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part B

AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part A

Part B:Pamiparib + Itraconazole

AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part B

AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part A

AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part B

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.

AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part A

AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part B

Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part A

Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part B

Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part A

Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part B

Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part A

Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part B

Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part A

All TEAEs

Serious TEAEs

Safety Analysis Set includes all participants who received at least 1 dose of pamiparib

Spots Global Cancer Trial Database for pamiparib 60 mg