ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 3 for:    small cell lung cancer BMN 673

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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:
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
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)
Hide 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
Not specified             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
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
Hide 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
Hide 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
1.Primary Outcome
Title Number of Participants With Objective Response
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide Description [Not Specified]
Time Frame Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide Description [Not Specified]
Time Frame Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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)
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)
Hide 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   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide 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
Show Other (Not Including Serious) Adverse Events Hide 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%)