Study of Talazoparib, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors

• ClinicalTrials.gov Identifier: NCT01286987
• Recruitment Status: Completed
• First Posted: February 1, 2011
• Results First Posted: January 10, 2019
• Last Update Posted: January 10, 2019
• Sponsor: Pfizer
• Collaborator: Medivation, Inc.
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Advanced or Recurrent Solid Tumors; Breast Neoplasms; Ovarian Cancer, Epithelial; Ewing Sarcoma; Small Cell Lung Carcinoma; Prostate Cancer; Pancreas Cancer
• Intervention: Drug: Talazoparib
• Enrollment: 113

Participant Flow

Recruitment Details
Pre-assignment Details	Study was conducted in two parts: Part 1 was dose escalation phase (to determine the maximum tolerated dose [MTD]) and Part 2 was the dose expansion phase conducted at MTD determined in Part 1. Participants were different in both of the Parts.

Arm/Group Title	Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day	Part 2: Talazoparib (Breast Cancer)	Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)	Part 2: Talazoparib (Pancreatic Cancer)	Part 2: Talazoparib (Ewing Cancer)	Part 2: Talazoparib (SCLC Cancer)	Part 2: Talazoparib (Prostate Cancer)
Arm/Group Description	Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with SCLC cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Period Title: Part 1: Dose Escalation
Started	3	3	3	3	3	6	6	6	6	0	0	0	0	0	0
Colorectal Cancer	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Prostate Cancer	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Ewing Cancer	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0
Pancreatic Cancer	1	2	0	0	0	0	0	0	0	0	0	0	0	0	0
Ovarian/ Peritoneal Cancer	1	1	2	3	3	4	4	3	2	0	0	0	0	0	0
Breast Cancer	0	0	0	0	0	1	2	2	3	0	0	0	0	0	0
Completed	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0
Not Completed	3	3	3	3	3	6	5	5	6	0	0	0	0	0	0
Reason Not Completed
Clinical Progression	1	1	0	1	1	1	0	2	1	0	0	0	0	0	0
Progressive Disease	2	2	3	2	1	5	5	3	5	0	0	0	0	0	0
Physician Decision	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Period Title: Part 2: Dose Expansion
Started	0	0	0	0	0	0	0	0	0	12	12	11	12	24	3
Treated	0	0	0	0	0	0	0	0	0	12	11	10	12	23	3
Completed	0	0	0	0	0	0	0	0	0	1	2	1	0	0	1
Not Completed	0	0	0	0	0	0	0	0	0	11	10	10	12	24	2
Reason Not Completed
Death	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Physician Decision	0	0	0	0	0	0	0	0	0	0	1	1	0	1	0
Other	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Progressive Disease	0	0	0	0	0	0	0	0	0	11	6	7	11	19	2
Clinical Progression	0	0	0	0	0	0	0	0	0	0	2	2	0	2	0
Withdrawal by Subject	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0

Baseline Characteristics

Arm/Group Title		Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day	Part 2: Talazoparib (Breast Cancer)	Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)	Part 2: Talazoparib (Pancreatic Cancer)	Part 2: Talazoparib (Ewing Cancer)	Part 2: Talazoparib (SCLC Cancer)	Part 2: Talazoparib (Prostate Cancer)	Total
Arm/Group Description		Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with SCLC cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Total of all reporting groups
Overall Number of Baseline Participants		3	3	3	3	3	6	6	6	6	12	11	10	12	23	3	110
Baseline Analysis Population Description		Safety analysis set included all enrolled participants who received at least 1 dose of talazoparib.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	3 participants	3 participants	3 participants	3 participants	3 participants	6 participants	6 participants	6 participants	6 participants	12 participants	11 participants	10 participants	12 participants	23 participants	3 participants	110 participants
		77.7 (3.51)	66.7 (9.07)	64.0 (9.64)	48.7 (11.50)	60.7 (5.77)	61.3 (19.00)	48.2 (8.66)	45.0 (18.25)	38.8 (13.73)	46.5 (11.47)	54.2 (10.93)	65.2 (7.71)	28.7 (15.18)	64.0 (10.45)	57.3 (8.14)	53.7 (16.80)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	3 participants	3 participants	3 participants	3 participants	6 participants	6 participants	6 participants	6 participants	12 participants	11 participants	10 participants	12 participants	23 participants	3 participants	110 participants
	Female	2 66.7%	1 33.3%	3 100.0%	3 100.0%	3 100.0%	5 83.3%	6 100.0%	5 83.3%	5 83.3%	11 91.7%	11 100.0%	4 40.0%	6 50.0%	11 47.8%	0 0.0%	76 69.1%
	Male	1 33.3%	2 66.7%	0 0.0%	0 0.0%	0 0.0%	1 16.7%	0 0.0%	1 16.7%	1 16.7%	1 8.3%	0 0.0%	6 60.0%	6 50.0%	12 52.2%	3 100.0%	34 30.9%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	3 participants	3 participants	3 participants	3 participants	3 participants	6 participants	6 participants	6 participants	6 participants	12 participants	11 participants	10 participants	12 participants	23 participants	3 participants	110 participants
American Indian or Alaska Native		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian		0	0	0	0	0	0	0	0	1	2	0	0	0	0	0	3
Black or African American		0	0	0	0	0	0	0	0	1	1	0	0	1	0	0	3
Native Hawaiian or Pacific Islander		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
White		3	3	3	3	3	6	5	5	4	9	11	10	10	23	3	101
Other		0	0	0	0	0	0	1	1	0	0	0	0	1	0	0	3

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Objective Response
Description	Objective response in participants was defined as the number of participants with complete response (CR) or partial response (PR) after treatment with talazoparib and maintained for at least 4 weeks (28 days) as assessed by response evaluation criteria in solid tumors (RECIST) version 1.1. CR defined as disappearance of all non-nodal target lesions (where all target lesions were recorded with a length of 0 millimeter [mm] on the case report form [CRF]) and the reduction of the shortest diameter of all nodal lesions to less than [<] 10 mm. PR was defined by a 30% or more decrease in the sum of the longest diameters (SLD) + sum of shortest diameters (SSD) of target lesions, taking as reference the baseline SLD+SSD.
Time Frame	From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)

Outcome Measure Data

Analysis Population Description

Response analysis population: all enrolled participants who had at least 1 dose of talazoparib, and measurable disease at baseline. Data for this outcome measure was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type.

Arm/Group Title	Part 1 and Part 2: Talazoparib (Breast Cancer)	Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)	Part 1 and Part 2: Talazoparib (Pancreatic Cancer)	Part 1 and Part 2: Talazoparib (Ewing Cancer)	Part 2: Talazoparib (SCLC Cancer)	Part 1 and Part 2: Talazoparib (Prostate Cancer)	Part 1: Talazoparib (Colorectal Cancer)
Arm/Group Description:	Participants with breast cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.	Participants with ovarian/ peritoneal cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.	Participants with pancreatic cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 1000 mcg/day.	Participants with ewing cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 1000 mcg/day, 1100 mcg/day.	Participants with small cell lung cancer (SCLC) cancer who received talazoparib capsules in Part 2 at a dose of 1000 mcg/day.	Participants with prostate cancer who received talazoparib capsules in Part 1 and 2 at a dose of 600 mcg/day.	Participants with colorectal cancer who received talazoparib capsules in Part 1 at a dose of either 25 mcg or 100 mcg/day.
Overall Number of Participants Analyzed	20	31	13	14	23	1	2
Measure Type: Number; Unit of Measure: participants
	8	12	2	0	2	0	0

2. Primary Outcome

Title	Number of Participants With Best Overall Response
Description	Best overall response: best response (in the order of confirmed CR, confirmed PR, stable disease [SD] and progressive disease [PD]) among all overall response as RECIST 1.1, recorded from date of first dose of talazoparib until participant withdrew from study/data cut-off date, whichever earlier. CR defined as disappearance of all non-nodal target lesions (where all target lesions recorded with a length of 0 mm on the CRF) and the reduction of the shortest diameter of all nodal lesions to < 10 mm. PR defined as at least a 30% decrease in sum of the diameters of target lesions, reference to baseline sum diameters. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD defined as at least a 20% increase in sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).
Time Frame	From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)

Outcome Measure Data

Analysis Population Description

Response analysis population: all enrolled participants who had at least 1 dose of talazoparib, and measurable disease at baseline. Data for this outcome measure was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type and was not planned to be analyzed for "Part 1: Colorectal Cancer" arm, as pre-specified in protocol.

Arm/Group Title	Part 1 and Part 2: Talazoparib (Breast Cancer)	Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)	Part 1 and Part 2: Talazoparib (Pancreatic Cancer)	Part 1 and Part 2: Talazoparib (Ewing Cancer)	Part 2: Talazoparib (SCLC Cancer)	Part 1 and Part 2: Talazoparib (Prostate Cancer)
Arm/Group Description:	Participants with breast cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.	Participants with ovarian/ peritoneal cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.	Participants with pancreatic cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 1000 mcg/day.	Participants with ewing cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 1000 mcg/day, 1100 mcg/day.	Participants with small cell lung cancer (SCLC) cancer who received talazoparib capsules in Part 2 at a dose of 1000 mcg/day.	Participants with prostate cancer who received talazoparib capsules in Part 1 and 2 at a dose of 600 mcg/day.
Overall Number of Participants Analyzed	20	31	13	14	23	1
Measure Type: Number; Unit of Measure: participants
Complete Response (CR)	1	1	0	0	0	0
Partial Response (PR)	7	11	2	0	2	0
Stable Disease (SD)	7	10	2	4	4	1
Progressive Disease (PD)	5	6	6	9	14	0

3. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as the time (in weeks) from the date of first dose of study drug to the earlier date of the documented PD or death due to any cause. PD as per RECIST 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).
Time Frame	Baseline, until PD or death due to any cause (maximum duration:1071 days for Part 1; 834 days for Part 2)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all enrolled participants who received at least 1 dose of talazoparib. Data for this outcome measure was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type and was not planned to be analyzed for "Part 1: Colorectal Cancer" arm, as pre-specified in protocol.

Arm/Group Title	Part 1 and Part 2: Talazoparib (Breast Cancer)	Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)	Part 1 and Part 2: Talazoparib (Pancreatic Cancer)	Part 1 and Part 2: Talazoparib (Ewing Cancer)	Part 2: Talazoparib (SCLC Cancer)	Part 1 and Part 2: Talazoparib (Prostate Cancer)
Arm/Group Description:	Participants with breast cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.	Participants with ovarian/ peritoneal cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.	Participants with pancreatic cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 1000 mcg/day.	Participants with ewing cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 1000 mcg/day, 1100 mcg/day.	Participants with small cell lung cancer (SCLC) cancer who received talazoparib capsules in Part 2 at a dose of 1000 mcg/day.	Participants with prostate cancer who received talazoparib capsules in Part 1 and 2 at a dose of 600 mcg/day.
Overall Number of Participants Analyzed	20	34	13	14	23	4
Median (95% Confidence Interval); Unit of Measure: weeks
	29.3; (12.1 to 43.4)	32.1; (18.9 to 38.6)	5.3; (2.4 to 21.3)	6.2; (3.1 to 14.0)	11.1; (4.3 to 13.0)	12.1; (12.0 to NA)

4. Primary Outcome

Title	Duration of Response
Description	Duration of response was defined as the time (in weeks) from the date of the first documented objective response confirmed at least 28 days later to the date of the first documented PD or date of death, whichever occurred first. PD as per RECIST version 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).
Time Frame	Baseline until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)

Outcome Measure Data

Analysis Population Description

Analysis performed on subset of response analysis population which included participants who had objective response. Data for outcome measure was planned to be analyzed combined for Part 1 and Part 2. "Overall number of participants analyzed" is zero (0) for arms of ewing, prostate, CLC cancer, since none of the participants had objective response.

Arm/Group Title	Part 1 and Part 2: Talazoparib (Breast Cancer)	Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)	Part 1 and Part 2: Talazoparib (Pancreatic Cancer)	Part 1 and Part 2: Talazoparib (Ewing Cancer)	Part 2: Talazoparib (SCLC Cancer)	Part 1 and Part 2: Talazoparib (Prostate Cancer)	Part 1: Talazoparib (Colorectal Cancer)
Arm/Group Description:	Participants with breast cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.	Participants with ovarian/ peritoneal cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.	Participants with pancreatic cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 1000 mcg/day.	Participants with ewing cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 1000 mcg/day, 1100 mcg/day.	Participants with small cell lung cancer (SCLC) cancer who received talazoparib capsules in Part 2 at a dose of 1000 mcg/day.	Participants with prostate cancer who received talazoparib capsules in Part 1 and 2 at a dose of 600 mcg/day.	Participants with colorectal cancer who received talazoparib capsules in Part 1 at a dose of either 25 mcg or 100 mcg/day.
Overall Number of Participants Analyzed	8	12	2	0	2	0	0
Median (95% Confidence Interval); Unit of Measure: weeks
	32.2; (20.1 to 64.1)	26.9; (15.7 to 35.1)	NA [1]; (21.6 to NA)		13.6; (12.0 to 15.3)

[1]

Median and Upper limit of 95% CI were not estimable due to the less number of participants with events

5. Primary Outcome

Title	Number of Participants With Stable Disease
Description	SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD defined as at least a 20% increase in sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).
Time Frame	Baseline, until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)

Outcome Measure Data

Analysis Population Description

Response analysis population: all enrolled participants who had at least 1 dose of talazoparib, and measurable disease at baseline. Data for this outcome measure was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type and was not planned to be analyzed for "Part 1: Colorectal Cancer" arm, as pre-specified in protocol.

Arm/Group Title	Part 1 and Part 2: Talazoparib (Breast Cancer)	Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)	Part 1 and Part 2: Talazoparib (Pancreatic Cancer)	Part 1 and Part 2: Talazoparib (Ewing Cancer)	Part 2: Talazoparib (SCLC Cancer)	Part 1 and Part 2: Talazoparib (Prostate Cancer)
Arm/Group Description:	Participants with breast cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.	Participants with ovarian/ peritoneal cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.	Participants with pancreatic cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 1000 mcg/day.	Participants with ewing cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 1000 mcg/day, 1100 mcg/day.	Participants with small cell lung cancer (SCLC) cancer who received talazoparib capsules in Part 2 at a dose of 1000 mcg/day.	Participants with prostate cancer who received talazoparib capsules in Part 1 and 2 at a dose of 600 mcg/day.
Overall Number of Participants Analyzed	20	31	13	14	23	1
Measure Type: Number; Unit of Measure: participants
	7	10	2	4	4	1

6. Primary Outcome

Title	Part 1: Maximum Tolerated Dose (MTD)
Description	The MTD was defined as the highest dose at which no more than 1 of 6 participants experienced a Dose Limiting Toxicity (DLT). DLT defined as any of the following occurring during cycle 1 of part 1 of study, Hematologic toxicity: Any grade 4 or higher hematologic adverse event, Grade 3 thrombocytopenia associated with grade 2 or higher haemorrhage, Grade 3 thrombocytopenia or neutropenia that led to interruption of dosing for 5 or more days. Nonhematologic toxicity: grade 3 or higher laboratory AE which was asymptomatic and rapidly reversible adverse events (returned to baseline or to grade 1 or lower within 7 days), Grade 3 nausea, vomiting, or diarrhea that could be medically managed to grade 2 or lower with anti-emetics and/or anti-diarrheals within 24 hours, Grade 3 fatigue that improved to grade 2 or lower in 5 days or less, Alopecia. Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
Time Frame	Cycle 1 (Day 1 up to Day 42)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of talazoparib.

Arm/Group Title	Part 1: Talazoparib: All Participants
Arm/Group Description:	All participants who received talazoparib capsules in part 1 at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day and 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed	39
Measure Type: Number; Unit of Measure: mcg/day
	1000

7. Primary Outcome

Title	Part 1: Recommended Part 2 Dose of Talazoparib
Description	The Recommended dose of talazoparib for use in Part 2 was determined in Part 1 (dose escalation) on the basis of the totality of safety, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond.
Time Frame	Baseline up to Cycle 50 (each cycle 28 days)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of talazoparib.

Arm/Group Title	Part 1: Talazoparib: All Participants
Arm/Group Description:	All participants who received talazoparib capsules in part 1 at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day and 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed	39
Measure Type: Number; Unit of Measure: mcg/day
	1000

8. Other Pre-specified Outcome

Title	Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to end of study (up to 1071 days for Part 1 and up to 834 days for Part 2) that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	Part 1: Baseline up to 1071 days; Part 2: Baseline up to 834 days

Outcome Measure Data

Analysis Population Description

Safety analyses set included all enrolled participants who received at least 1 dose of talazoparib.

Arm/Group Title	Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day	Part 2: Talazoparib (Breast Cancer)	Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)	Part 2: Talazoparib (Pancreatic Cancer)	Part 2: Talazoparib (Ewing Cancer)	Part 2: Talazoparib (SCLC Cancer)	Part 2: Talazoparib (Prostate Cancer)
Arm/Group Description:	Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants with small cell lung cancer (SCLC) cancer who received talazoparib capsules in Part 2 at a dose of 1000 mcg/day.	Participants with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed	3	3	3	3	3	6	6	6	6	12	11	10	12	23	3
Measure Type: Number; Unit of Measure: participants
AEs	2	3	2	3	3	6	6	6	6	12	11	10	12	21	2
SAEs	1	2	2	3	0	2	3	1	3	2	5	6	4	8	0

9. Other Pre-specified Outcome

Title	Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
Description	[Not Specified]
Time Frame	Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints.

Arm/Group Title		Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day
Arm/Group Description:		Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed		3	3	3	3	3	6	6	6	6
Mean (Standard Deviation); Unit of Measure: picograms per milliliter (pg/mL)
Cycle 1 Day 1	Number Analyzed	3 participants	3 participants	3 participants	3 participants	3 participants	6 participants	6 participants	5 participants	6 participants
		60.0 (15.9)	79.7 (7.50)	214 (50.9)	788 (369)	1830 (699)	4100 (1400)	6100 (3060)	10600 (4220)	13200 (3220)
Cycle 1 Day 35	Number Analyzed	3 participants	2 participants	2 participants	3 participants	3 participants	6 participants	5 participants	6 participants	4 participants
		300 (78.8)	615 (74.2)	1880 (332)	5620 (3530)	6560 (1500)	11300 (3230)	15400 (1540)	21000 (7990)	23400 (4810)

10. Other Pre-specified Outcome

Title	Part 2: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
Description	[Not Specified]
Time Frame	Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1

Outcome Measure Data

Analysis Population Description

The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. PK data was planned to be reported for the overall participants in Part 2, as pre-specified in protocol.

Arm/Group Title		Part 2: Talazoparib 1000 mcg
Arm/Group Description:		All participants with either breast, ovarian/peritoneal, pancreatic, ewing, SCLC, or prostate cancer who received talazoparib capsules at a dose of 1000 mcg/day in Part 2.
Overall Number of Participants Analyzed		70
Mean (Standard Deviation); Unit of Measure: pg/mL
Cycle 1 Day 1	Number Analyzed	70 participants
		8480 (3890)
Cycle 2 Day 1	Number Analyzed	41 participants
		17700 (5790)

11. Other Pre-specified Outcome

Title	Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib
Description	[Not Specified]
Time Frame	Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35

Outcome Measure Data

Analysis Population Description

The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints.

Arm/Group Title		Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day
Arm/Group Description:		Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed		3	3	3	3	3	6	6	6	6
Median (Full Range); Unit of Measure: hours
Cycle 1 Day 1	Number Analyzed	3 participants	3 participants	3 participants	3 participants	3 participants	6 participants	6 participants	5 participants	6 participants
		7.92; (1.95 to 9.95)	1.00; (0.800 to 1.02)	1.02; (1.00 to 3.98)	1.03; (1.00 to 2.32)	2.03; (0.750 to 2.95)	0.835; (0.750 to 1.95)	2.00; (1.02 to 9.98)	1.03; (0.730 to 2.07)	1.00; (0.730 to 2.05)
Cycle 1 Day 35	Number Analyzed	3 participants	2 participants	2 participants	3 participants	3 participants	6 participants	5 participants	6 participants	4 participants
		1.02; (0.580 to 3.98)	5.43; (0.770 to 10.1)	0.785; (0.750 to 0.820)	1.97; (1.00 to 3.02)	0.980; (0.750 to 2.00)	1.04; (0.730 to 5.98)	1.02; (0.970 to 2.07)	1.02; (0.750 to 2.00)	1.48; (0.980 to 2.00)

12. Other Pre-specified Outcome

Title	Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib
Description	[Not Specified]
Time Frame	Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1

Outcome Measure Data

Analysis Population Description

The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. PK data was planned to be reported for the overall participants in Part 2, as pre-specified in protocol.

Arm/Group Title		Part 2: Talazoparib 1000 mcg
Arm/Group Description:		All participants with either breast, ovarian/peritoneal, pancreatic, ewing, SCLC, or prostate cancer who received talazoparib capsules at a dose of 1000 mcg/day in Part 2.
Overall Number of Participants Analyzed		70
Median (Full Range); Unit of Measure: hours
Cycle 1 Day 1	Number Analyzed	70 participants
		1.00; (0.500 to 4.07)
Cycle 2 Day 1	Number Analyzed	41 participants
		1.07; (0.500 to 6.05)

13. Other Pre-specified Outcome

Title	Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib
Description	Area under the plasma concentration time-curve from zero to the time of last measured concentration (AUC0-last).
Time Frame	Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1

Outcome Measure Data

Analysis Population Description

The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints.

Arm/Group Title	Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day
Arm/Group Description:	Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed	3	3	3	3	3	6	6	6	6
Mean (Standard Deviation); Unit of Measure: picograms*hour per mililiter (pg*hr/mL)
	3600 (1360)	5340 (1960)	16600 (5320)	39300 (11700)	43700 (15000)	97900 (30000)	160000 (66100)	182000 (62400)	201000 (93400)

14. Other Pre-specified Outcome

Title	Part 2: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib
Description	Area under the plasma concentration time-curve from zero to the time of last measured concentration (AUC0-last).
Time Frame	Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1

Outcome Measure Data

Analysis Population Description

The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. PK data was planned to be reported for the overall participants in Part 2, as pre-specified in protocol.

Arm/Group Title		Part 2: Talazoparib 1000 mcg
Arm/Group Description:		All participants with either breast, ovarian/peritoneal, pancreatic, ewing, SCLC, or prostate cancer who received talazoparib capsules at a dose of 1000 mcg/day in Part 2.
Overall Number of Participants Analyzed		70
Mean (Standard Deviation); Unit of Measure: pg*hr/mL
Cycle 1 Day 1	Number Analyzed	70 participants
		19100 (8850)
Cycle 2 Day 1	Number Analyzed	41 participants
		50200 (16300)

15. Other Pre-specified Outcome

Title	Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib
Description	[Not Specified]
Time Frame	Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 35

Outcome Measure Data

Analysis Population Description

The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this outcome measure was not planned to be analyzed for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day
Arm/Group Description:	Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed	3	3	3	3	3	6	6	6	6
Mean (Standard Deviation); Unit of Measure: pg/mL
	169 (58.0)	299 (133)	1020 (107)	2880 (1710)	2230 (957)	3470 (1050)	3180 (802)	3720 (1590)	2910 (803)

16. Other Pre-specified Outcome

Title	Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib
Description	AUC (0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Time Frame	Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1

Outcome Measure Data

Analysis Population Description

The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this outcome measure was not planned to be analyzed for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day
Arm/Group Description:	Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed	3	3	3	3	3	6	6	6	6
Mean (Standard Deviation); Unit of Measure: pg*hr/mL
	5330 (1840)	8320 (1960)	37600 (6620)	92700 (48500)	60100 (15900)	120000 (26000)	188000 (85700)	200000 (64000)	235000 (111000)

17. Other Pre-specified Outcome

Title	Part 1: Terminal Half-Life (t1/2) of Talazoparib
Description	T1/2 is the time measured for the plasma concentration of talazoparib to decrease by one half.
Time Frame	Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35

Outcome Measure Data

Analysis Population Description

The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this outcome measure was not planned to be analyzed for Part 2, as pre-specified in protocol.

Arm/Group Title		Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day
Arm/Group Description:		Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed		3	3	3	3	3	6	6	6	6
Mean (Standard Deviation); Unit of Measure: Hours
Cycle 1 Day 1	Number Analyzed	3 participants	3 participants	3 participants	3 participants	3 participants	6 participants	6 participants	5 participants	6 participants
		100 (11.9)	129 (42.6)	229 (158)	212 (126)	102 (27.2)	58.6 (17.3)	60.4 (10.9)	52.9 (13.4)	71.0 (20.6)
Cycle 1 Day 35	Number Analyzed	2 participants	2 participants	2 participants	3 participants	3 participants	6 participants	5 participants	6 participants	4 participants
		107 (84.2)	132 (12.3)	98.2 (4.83)	50.9 (19.1)	90.7 (32.7)	63.7 (12.7)	71.0 (14.5)	50.0 (16.6)	52.8 (23.2)

18. Other Pre-specified Outcome

Title	Part 1: Apparent Oral Clearance (CL/F) of Talazoparib
Description	Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) was influenced by the fraction of the dose absorbed.
Time Frame	Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1

Outcome Measure Data

Analysis Population Description

The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this outcome measure was not planned to be analyzed for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day
Arm/Group Description:	Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed	3	3	3	3	3	6	6	6	6
Mean (Standard Deviation); Unit of Measure: liter/hour
	5.17 (2.10)	6.27 (1.66)	2.72 (0.532)	2.61 (1.35)	6.95 (1.71)	5.19 (0.990)	5.49 (2.08)	5.39 (1.59)	5.32 (1.64)

19. Other Pre-specified Outcome

Title	Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib
Description	Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was influenced by the fraction absorbed.
Time Frame	Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35

Outcome Measure Data

Analysis Population Description

The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this outcome measure was not planned to be analyzed for Part 2, as pre-specified in protocol.

Arm/Group Title		Part 1: Talazoparib 25 mcg/Day	Part 1: Talazoparib 50 mcg/Day	Part 1: Talazoparib 100 mcg/Day	Part 1: Talazoparib 200 mcg/Day	Part 1: Talazoparib 400 mcg/Day	Part 1: Talazoparib 600 mcg/Day	Part 1: Talazoparib 900 mcg/Day	Part 1: Talazoparib 1000 mcg/Day	Part 1: Talazoparib 1100 mcg/Day
Arm/Group Description:		Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.	Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
Overall Number of Participants Analyzed		3	3	3	3	3	6	6	6	6
Mean (Standard Deviation); Unit of Measure: liter
Cycle 1 Day 1	Number Analyzed	3 participants	3 participants	3 participants	3 participants	3 participants	6 participants	6 participants	5 participants	6 participants
		756 (351)	1240 (742)	839 (487)	678 (217)	1050 (431)	441 (143)	468 (169)	415 (170)	549 (232)
Cycle 1 Day 35	Number Analyzed	2 participants	2 participants	2 participants	3 participants	3 participants	6 participants	5 participants	6 participants	4 participants
		1070 (971)	1020 (345)	475 (47.8)	264 (249)	818 (326)	477 (136)	604 (169)	373 (144)	472 (254)

Adverse Events

Time Frame

Baseline up to end of study (maximum duration: 1071 days for Part 1; 834 days for Part 2)

Adverse Event Reporting Description

Analysis performed on safety population. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.

Arm/Group Title

Part 1: Talazoparib 25 mcg/Day

Part 1: Talazoparib 50 mcg/Day

Part 1: Talazoparib 100 mcg/Day

Part 1: Talazoparib 200 mcg/Day

Part 1: Talazoparib 400 mcg/Day

Part 1: Talazoparib 600 mcg/Day

Part 1: Talazoparib 900 mcg/Day

Part 1: Talazoparib 1000 mcg/Day

Part 1: Talazoparib 1100 mcg/Day

Part 2: Talazoparib (Breast Cancer)

Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)

Part 2: Talazoparib (Pancreatic Cancer)

Part 2: Talazoparib (Ewing Cancer)

Part 2: Talazoparib (SCLC Cancer)

Part 2: Talazoparib (Prostate Cancer)

Arm/Group Description

Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants with SCLC cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

Participants with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

All-Cause Mortality

Part 1: Talazoparib 25 mcg/Day

Part 1: Talazoparib 50 mcg/Day

Part 1: Talazoparib 100 mcg/Day

Part 1: Talazoparib 200 mcg/Day

Part 1: Talazoparib 400 mcg/Day

Part 1: Talazoparib 600 mcg/Day

Part 1: Talazoparib 900 mcg/Day

Part 1: Talazoparib 1000 mcg/Day

Part 1: Talazoparib 1100 mcg/Day

Part 2: Talazoparib (Breast Cancer)

Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)

Part 2: Talazoparib (Pancreatic Cancer)

Part 2: Talazoparib (Ewing Cancer)

Part 2: Talazoparib (SCLC Cancer)

Part 2: Talazoparib (Prostate Cancer)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Total

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

Serious Adverse Events

Part 1: Talazoparib 25 mcg/Day

Part 1: Talazoparib 50 mcg/Day

Part 1: Talazoparib 100 mcg/Day

Part 1: Talazoparib 200 mcg/Day

Part 1: Talazoparib 400 mcg/Day

Part 1: Talazoparib 600 mcg/Day

Part 1: Talazoparib 900 mcg/Day

Part 1: Talazoparib 1000 mcg/Day

Part 1: Talazoparib 1100 mcg/Day

Part 2: Talazoparib (Breast Cancer)

Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)

Part 2: Talazoparib (Pancreatic Cancer)

Part 2: Talazoparib (Ewing Cancer)

Part 2: Talazoparib (SCLC Cancer)

Part 2: Talazoparib (Prostate Cancer)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Total

1/3 (33.33%)

2/3 (66.67%)

2/3 (66.67%)

3/3 (100.00%)

0/3 (0.00%)

2/6 (33.33%)

3/6 (50.00%)

2/6 (33.33%)

3/6 (50.00%)

2/12 (16.67%)

5/11 (45.45%)

6/10 (60.00%)

4/12 (33.33%)

8/23 (34.78%)

0/3 (0.00%)

Blood and lymphatic system disorders

Anaemia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Thrombocytopenia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

1/12 (8.33%)

0/23 (0.00%)

0/3 (0.00%)

Cardiac disorders

Supraventricular tachycardia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Ventricular tachycardia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Endocrine disorders

Inappropriate antidiuretic hormone secretion * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Gastrointestinal disorders

Ascites * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Abdominal pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Dyspepsia * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Intestinal obstruction * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

2/11 (18.18%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Nausea * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Rectal haemorrhage * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Vomiting * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Small intestinal obstruction * 1

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

2/11 (18.18%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

General disorders

Pyrexia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Disease progression * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Hepatobiliary disorders

Bile duct obstruction * 1

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Hyperbilirubinaemia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Infections and infestations

Bacteraemia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Community acquired infection * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Sepsis * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Device related infection * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

2/11 (18.18%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Lung infection * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Otitis media * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

1/12 (8.33%)

0/23 (0.00%)

0/3 (0.00%)

Pneumonia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Injury, poisoning and procedural complications

Anastomotic stenosis * 1

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Transfusion reaction * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Pubis fracture * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Investigations

Transaminases increased * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Metabolism and nutrition disorders

Hyponatraemia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

2/23 (8.70%)

0/3 (0.00%)

Hypokalaemia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Musculoskeletal and connective tissue disorders

Bone pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Invasive ductal breast carcinoma * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Metastases to central nervous system * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Pancreatic carcinoma * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Tumour associated fever * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Ovarian neoplasm * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Cancer pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

1/12 (8.33%)

0/23 (0.00%)

0/3 (0.00%)

Metastases to lung * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Nervous system disorders

Neuralgia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Cerebrovascular accident * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Renal and urinary disorders

Acute kidney injury * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Haematuria * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pleural effusion * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Pulmonary embolism * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Dyspnoea * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

2/12 (16.67%)

0/23 (0.00%)

0/3 (0.00%)

Haemothorax * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Respiratory failure * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

1/12 (8.33%)

0/23 (0.00%)

0/3 (0.00%)

Vascular disorders

Hypotension * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 20.0

Other (Not Including Serious) Adverse Events

Frequency Threshold for Reporting Other Adverse Events

0%

Part 1: Talazoparib 25 mcg/Day

Part 1: Talazoparib 50 mcg/Day

Part 1: Talazoparib 100 mcg/Day

Part 1: Talazoparib 200 mcg/Day

Part 1: Talazoparib 400 mcg/Day

Part 1: Talazoparib 600 mcg/Day

Part 1: Talazoparib 900 mcg/Day

Part 1: Talazoparib 1000 mcg/Day

Part 1: Talazoparib 1100 mcg/Day

Part 2: Talazoparib (Breast Cancer)

Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)

Part 2: Talazoparib (Pancreatic Cancer)

Part 2: Talazoparib (Ewing Cancer)

Part 2: Talazoparib (SCLC Cancer)

Part 2: Talazoparib (Prostate Cancer)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Total

2/3 (66.67%)

3/3 (100.00%)

2/3 (66.67%)

3/3 (100.00%)

3/3 (100.00%)

6/6 (100.00%)

6/6 (100.00%)

6/6 (100.00%)

6/6 (100.00%)

12/12 (100.00%)

11/11 (100.00%)

10/10 (100.00%)

12/12 (100.00%)

20/23 (86.96%)

3/3 (100.00%)

Blood and lymphatic system disorders

Anaemia vitamin B12 deficiency * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Neutropenia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

2/6 (33.33%)

1/6 (16.67%)

3/12 (25.00%)

3/11 (27.27%)

3/10 (30.00%)

0/12 (0.00%)

3/23 (13.04%)

0/3 (0.00%)

Thrombocytopenia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

1/6 (16.67%)

2/6 (33.33%)

1/6 (16.67%)

2/6 (33.33%)

1/12 (8.33%)

3/11 (27.27%)

0/10 (0.00%)

3/12 (25.00%)

8/23 (34.78%)

0/3 (0.00%)

Anaemia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

4/6 (66.67%)

2/6 (33.33%)

5/12 (41.67%)

6/11 (54.55%)

3/10 (30.00%)

5/12 (41.67%)

8/23 (34.78%)

1/3 (33.33%)

Leukopenia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

1/6 (16.67%)

2/12 (16.67%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Lymph node pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Thrombocytosis * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Lymphadenopathy * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Lymphopenia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

1/12 (8.33%)

0/23 (0.00%)

0/3 (0.00%)

Cardiac disorders

Atrial fibrillation * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Bundle branch block left * 1

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Tachycardia * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

1/12 (8.33%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Pericardial effusion * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Ventricular tachycardia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Angina pectoris * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Supraventricular tachycardia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Ear and labyrinth disorders

Ear pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Ear pruritus * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Ear swelling * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Ear discomfort * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Tinnitus * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

2/12 (16.67%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Eye disorders

Cataract * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Eye pruritus * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Lacrimation increased * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Eye pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Visual impairment * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Eye swelling * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Vision blurred * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

2/6 (33.33%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

1/12 (8.33%)

0/23 (0.00%)

0/3 (0.00%)

Gastrointestinal disorders

Abdominal distension * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

2/6 (33.33%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

1/12 (8.33%)

1/23 (4.35%)

0/3 (0.00%)

Abdominal pain * 1

0/3 (0.00%)

1/3 (33.33%)

1/3 (33.33%)

2/3 (66.67%)

1/3 (33.33%)

2/6 (33.33%)

0/6 (0.00%)

1/6 (16.67%)

2/6 (33.33%)

3/12 (25.00%)

4/11 (36.36%)

3/10 (30.00%)

1/12 (8.33%)

2/23 (8.70%)

0/3 (0.00%)

Abdominal pain lower * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Ascites * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Constipation * 1

0/3 (0.00%)

1/3 (33.33%)

1/3 (33.33%)

2/3 (66.67%)

2/3 (66.67%)

1/6 (16.67%)

3/6 (50.00%)

1/6 (16.67%)

1/6 (16.67%)

4/12 (33.33%)

4/11 (36.36%)

2/10 (20.00%)

2/12 (16.67%)

5/23 (21.74%)

2/3 (66.67%)

Diarrhoea * 1

2/3 (66.67%)

1/3 (33.33%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

1/6 (16.67%)

2/6 (33.33%)

2/6 (33.33%)

1/6 (16.67%)

4/12 (33.33%)

4/11 (36.36%)

1/10 (10.00%)

2/12 (16.67%)

0/23 (0.00%)

0/3 (0.00%)

Dry mouth * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

1/10 (10.00%)

1/12 (8.33%)

1/23 (4.35%)

0/3 (0.00%)

Flatulence * 1

0/3 (0.00%)

2/3 (66.67%)

1/3 (33.33%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

2/6 (33.33%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

1/10 (10.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Nausea * 1

1/3 (33.33%)

1/3 (33.33%)

1/3 (33.33%)

3/3 (100.00%)

2/3 (66.67%)

4/6 (66.67%)

5/6 (83.33%)

2/6 (33.33%)

1/6 (16.67%)

5/12 (41.67%)

10/11 (90.91%)

4/10 (40.00%)

3/12 (25.00%)

9/23 (39.13%)

0/3 (0.00%)

Toothache * 1

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Vomiting * 1

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

2/3 (66.67%)

0/3 (0.00%)

2/6 (33.33%)

1/6 (16.67%)

2/6 (33.33%)

2/6 (33.33%)

3/12 (25.00%)

3/11 (27.27%)

0/10 (0.00%)

2/12 (16.67%)

5/23 (21.74%)

0/3 (0.00%)

Abdominal pain upper * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

2/6 (33.33%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

3/11 (27.27%)

2/10 (20.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Dyspepsia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

2/6 (33.33%)

1/6 (16.67%)

0/6 (0.00%)

2/6 (33.33%)

3/12 (25.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

2/23 (8.70%)

0/3 (0.00%)

Frequent bowel movements * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Gastritis * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Intestinal obstruction * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Oesophagitis ulcerative * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Stomatitis * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

2/12 (16.67%)

2/11 (18.18%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Abnormal faeces * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Dental caries * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Dysphagia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Femoral hernia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Gastrooesophageal reflux disease * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Glossodynia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Haematochezia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Haemorrhoids * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Inguinal hernia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Oral pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

1/6 (16.67%)

0/6 (0.00%)

1/12 (8.33%)

1/11 (9.09%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Abdominal discomfort * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

3/11 (27.27%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Abdominal tenderness * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Aphthous ulcer * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

2/12 (16.67%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Eructation * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Food poisoning * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

1/3 (33.33%)

Hypoaesthesia oral * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

2/12 (16.67%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Mouth ulceration * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Oral mucosal erythema * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Odynophagia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Paraesthesia oral * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Oesophagitis * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

General disorders

Early satiety * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Fatigue * 1

0/3 (0.00%)

0/3 (0.00%)

2/3 (66.67%)

2/3 (66.67%)

3/3 (100.00%)

3/6 (50.00%)

3/6 (50.00%)

5/6 (83.33%)

1/6 (16.67%)

6/12 (50.00%)

9/11 (81.82%)

4/10 (40.00%)

3/12 (25.00%)

12/23 (52.17%)

0/3 (0.00%)

Chest pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Influenza like illness * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Mucosal inflammation * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

1/6 (16.67%)

1/6 (16.67%)

1/6 (16.67%)

1/6 (16.67%)

3/12 (25.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

2/6 (33.33%)

0/6 (0.00%)

1/6 (16.67%)

1/6 (16.67%)

2/12 (16.67%)

1/11 (9.09%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Peripheral swelling * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Asthenia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

1/12 (8.33%)

1/23 (4.35%)

0/3 (0.00%)

Axillary pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

1/12 (8.33%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Catheter site pain * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

2/11 (18.18%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Chest discomfort * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Chills * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Local swelling * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Medical device site reaction * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Oedema peripheral * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

4/11 (36.36%)

0/10 (0.00%)

2/12 (16.67%)

0/23 (0.00%)

0/3 (0.00%)

Pyrexia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

3/6 (50.00%)

3/6 (50.00%)

1/6 (16.67%)

2/12 (16.67%)

2/11 (18.18%)

2/10 (20.00%)

1/12 (8.33%)

1/23 (4.35%)

0/3 (0.00%)

Discomfort * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Feeling hot * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

3/11 (27.27%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Sensation of foreign body * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Temperature intolerance * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/11 (9.09%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Feeling abnormal * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Feeling cold * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Localised oedema * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Nodule * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

1/10 (10.00%)

1/12 (8.33%)

0/23 (0.00%)

0/3 (0.00%)

Oedema * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

1/23 (4.35%)

0/3 (0.00%)

Thirst * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

1/12 (8.33%)

0/23 (0.00%)

0/3 (0.00%)

Hepatobiliary disorders

Cholangitis * 1

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Bile duct obstruction * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Hyperbilirubinaemia * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

2/10 (20.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Immune system disorders

Seasonal allergy * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Autoimmune disorder * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Infections and infestations

Bronchitis * 1

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Lower respiratory tract infection * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Skin candida * 1

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Cellulitis * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

1/6 (16.67%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Influenza * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Sepsis * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Urinary tract infection * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

2/6 (33.33%)

0/6 (0.00%)

2/6 (33.33%)

0/6 (0.00%)

3/12 (25.00%)

3/11 (27.27%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Viral upper respiratory tract infection * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

1/6 (16.67%)

1/6 (16.67%)

1/6 (16.67%)

1/6 (16.67%)

3/12 (25.00%)

3/11 (27.27%)

1/10 (10.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Breast abscess * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Fungal skin infection * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Gastroenteritis * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

0/23 (0.00%)

0/3 (0.00%)

Oral candidiasis * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

0/11 (0.00%)

0/10 (0.00%)

0/12 (0.00%)

2/23 (8.70%)

0/3 (0.00%)

Rhinitis * 1

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/6 (16.67%)