Trial Outcomes & Findings for Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer (NCT NCT03994211)

NCT ID: NCT03994211

Last Updated: 2024-10-26

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 25 participants
• Primary outcome timeframe: 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
• Results posted on: 2024-10-26

Participant Flow

This study consisted of a core phase and an extension phase. A total of 25 participants were enrolled in Poland, Moldova, Slovakia, and Georgia.

The screening period consisted of Days -28 to -1.

Participant milestones

Measure	Core Phase: Arm A: Pamiparib + Rifampin 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 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	Extension Phase 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
Core Phase STARTED	12	13	0
Core Phase COMPLETED	12	12	0
Core Phase NOT COMPLETED	0	1	0
Extension Phase STARTED	0	0	24
Extension Phase COMPLETED	0	0	0
Extension Phase NOT COMPLETED	0	0	24

Reasons for withdrawal

Measure	Core Phase: Arm A: Pamiparib + Rifampin 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 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	Extension Phase 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
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

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

Baseline characteristics by cohort

Measure	Core Phase: Arm A: Pamiparib + Rifampin n=12 Participants 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	Core Phase: Arm B: Pamiparib + Itraconazole n=13 Participants 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 n=25 Participants Total of all reporting groups
Age, Continuous	58.7 years STANDARD_DEVIATION 10.73 • n=5 Participants	62.6 years STANDARD_DEVIATION 12.96 • n=7 Participants	60.7 years STANDARD_DEVIATION 11.87 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=11 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=11 Participants 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	Extension Phase 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
Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part A	1970 ng/mL Interval 1060.0 to 2700.0	1820 ng/mL Interval 1170.0 to 2500.0	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=12 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=12 Participants 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	Extension Phase 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
Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part B	730.5 ng/mL Interval 374.0 to 1130.0	752.5 ng/mL Interval 302.0 to 1130.0	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=11 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=11 Participants 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	Extension Phase 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
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) Interval 14680.8 to 46910.6	18351 hours*nanograms/milliLiter (h*ng/mL) Interval 11097.3 to 24186.8	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=12 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=12 Participants 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	Extension Phase 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
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) Interval 1797.5 to 20891.1	8894 hours*nanograms/milliLiter (h*ng/mL) Interval 1528.1 to 19356.9	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=9 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=11 Participants 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	Extension Phase 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
AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part A	28142 hr*ng/mL Interval 14776.0 to 51942.0	18563 hr*ng/mL Interval 11183.0 to 25615.0	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=12 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=12 Participants 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	Extension Phase 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
AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part B	10072 hr*ng/mL Interval 1828.4 to 25529.9	9353 hr*ng/mL Interval 1541.9 to 23171.0	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=11 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=11 Participants 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	Extension Phase 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
AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part A	14642.90 hr*ng/mL Interval 9502.6 to 20992.6	12262.61 hr*ng/mL Interval 7908.4 to 15230.0	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=12 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=12 Participants 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	Extension Phase 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
AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part B	5097.06 hr*ng/mL Interval 1640.4 to 8313.2	4647.47 hr*ng/mL Interval 1413.5 to 8879.2	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=11 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=11 Participants 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	Extension Phase 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
AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part A	11821.06 hr*ng/mL Interval 7678.6 to 16561.4	10515.14 hr*ng/mL Interval 6888.8 to 12813.6	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=12 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=12 Participants 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	Extension Phase 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
AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part B	4267.86 hr*ng/mL Interval 1525.3 to 6350.2	3812.39 hr*ng/mL Interval 1315.8 to 7325.8	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=11 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=11 Participants 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	Extension Phase 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
Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part A	2.000 hours Interval 1.0 to 4.0	2.000 hours Interval 1.0 to 4.05	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=12 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=12 Participants 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	Extension Phase 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
Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part B	2.000 hours Interval 0.98 to 4.02	1.000 hours Interval 0.95 to 2.02	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=9 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=11 Participants 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	Extension Phase 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
Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part A	13.381 hours Interval 6.77 to 20.01	7.667 hours Interval 5.09 to 11.39	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=12 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=12 Participants 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	Extension Phase 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
Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part B	9.290 hours Interval 4.48 to 19.14	11.179 hours Interval 3.69 to 19.44	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=9 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=9 Participants 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	Extension Phase 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
Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part A	2.132 Liters/hour (L/h) Interval 1.16 to 4.06	3.232 Liters/hour (L/h) Interval 2.34 to 5.37	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=11 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=9 Participants 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	Extension Phase 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
Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part B	1.987 Liters/hour (L/h) Interval 0.78 to 10.94	2.147 Liters/hour (L/h) Interval 0.86 to 12.97	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=9 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=9 Participants 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	Extension Phase 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
Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part A	35.491 Liters Interval 22.61 to 51.12	37.712 Liters Interval 29.88 to 53.98	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part A: Pamiparib n=12 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=12 Participants 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	Extension Phase 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
Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part B	34.697 Liters Interval 21.6 to 70.69	37.589 Liters Interval 24.21 to 69.03	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Part A: Pamiparib n=12 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=13 Participants 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	Extension Phase n=24 Participants 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
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) All TEAEs	5 Number of participants	6 Number of participants	18 Number of participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Serious TEAEs	0 Number of participants	1 Number of participants	2 Number of participants

SECONDARY outcome

Timeframe: Up to approximately 26 months

Population: Safety Population

Outcome measures

Measure	Part A: Pamiparib n=12 Participants Participants received 60 mg pamiparib orally on Days 1 and 10 fasting 8 hours pre-dose	Part A: Pamiparib + Rifampin n=13 Participants 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	Extension Phase n=24 Participants 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
Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations Laboratory Assessments	0 Number of participants	0 Number of participants	0 Number of participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations Vital Signs	0 Number of participants	0 Number of participants	0 Number of participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations Physical Examinations	0 Number of participants	0 Number of participants	0 Number of participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations ECG Parameters	0 Number of participants	0 Number of participants	0 Number of participants

Adverse Events

Core Phase: Arm A: Pamiparib + Rifampin

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Core Phase: Arm B: Pamiparib + Itraconazole

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Extension Phase

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Core Phase: Arm A: Pamiparib + Rifampin n=12 participants at risk 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 B: Pamiparib + Itraconazole n=13 participants at risk 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	Extension Phase n=24 participants at risk 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
Blood and lymphatic system disorders Anaemia	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 3 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Intestinal obstruction	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	7.7% 1/13 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/24 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Vomiting	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)

Other adverse events

Measure	Core Phase: Arm A: Pamiparib + Rifampin n=12 participants at risk 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 B: Pamiparib + Itraconazole n=13 participants at risk 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	Extension Phase n=24 participants at risk 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
Blood and lymphatic system disorders Anaemia	8.3% 1/12 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	7.7% 1/13 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	45.8% 11/24 • Number of events 15 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Blood and lymphatic system disorders Macrocytosis	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Blood and lymphatic system disorders Neutropenia	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Cardiac disorders Palpitations	8.3% 1/12 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/24 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Endocrine disorders Hyperthyroidism	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Eye disorders Retinal haemorrhage	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Abdominal distension	8.3% 1/12 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/24 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Abdominal pain	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Duodenogastric reflux	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Dyspepsia	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Eructation	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	7.7% 1/13 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/24 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Gastritis	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Gastritis erosive	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Gingival bleeding	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Nausea	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	15.4% 2/13 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	12.5% 3/24 • Number of events 4 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Gastrointestinal disorders Vomiting	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	15.4% 2/13 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	12.5% 3/24 • Number of events 4 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
General disorders Catheter site inflammation	8.3% 1/12 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/24 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
General disorders Fatigue	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	12.5% 3/24 • Number of events 5 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
General disorders Oedema peripheral	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Hepatobiliary disorders Jaundice	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Infections and infestations Bronchitis	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Infections and infestations Influenza	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Infections and infestations Rhinitis	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations Alanine aminotransferase increased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	7.7% 1/13 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations Aspartate aminotransferase increased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	7.7% 1/13 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations Bilirubin conjugated increased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations Blood bilirubin increased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations Blood creatinine increased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations Blood urea increased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations C-reactive protein increased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations Lymphocyte count decreased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations Neutrophil count decreased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations Platelet count decreased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations Weight decreased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Investigations White blood cell count decreased	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	12.5% 3/24 • Number of events 3 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Metabolism and nutrition disorders Folate deficiency	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Metabolism and nutrition disorders Iron deficiency	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	8.3% 2/24 • Number of events 2 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Musculoskeletal and connective tissue disorders Joint swelling	8.3% 1/12 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Nervous system disorders Syncope	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Psychiatric disorders Insomnia	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	7.7% 1/13 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/24 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Renal and urinary disorders Dysuria	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Renal and urinary disorders Hydronephrosis	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Respiratory, thoracic and mediastinal disorders Increased upper airway secretion	8.3% 1/12 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/24 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	7.7% 1/13 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/24 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/12 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	0.00% 0/13 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)	4.2% 1/24 • Number of events 1 • From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)

Additional Information

Study Director

BeiGene

Phone: +1-877-828-5568

Email: clinicaltrials@beigene.com

Results disclosure agreements

• Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information \& may request a further delay to protect its IP rights.
• Publication restrictions are in place

Restriction type: OTHER