Trial Outcomes & Findings for A Phase 2, 2-Stage, 2-Cohort Study of Talazoparib (BMN 673), in Locally Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (ABRAZO Study) (NCT NCT02034916)

NCT ID: NCT02034916

Last Updated: 2019-10-14

Results Overview

ORR: Percentage of participants with a confirmed best overall complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1). CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to less than (\<) 10 millimeter (mm) in short axis. PR: Greater than or equal to (\>=) 30 percent (%) decrease in sum of diameters of target lesions, compared to the sum at baseline. Response evaluation was done by an independent radiology facility (IRF).

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 84 participants
• Primary outcome timeframe: From randomization until data cutoff date (01 Sep 2016)
• Results posted on: 2019-10-14

Participant Flow

In this study, enrollment of participants was to be done in 2 stages for each of the 2 cohorts. Sufficient responses in each cohort were observed such that enrollment could proceed to Stage 2 for both cohorts. However, due to Sponsor decision, enrollment in the overall trial was terminated early.

Participant milestones

Measure	Cohort 1: Talazoparib 1 mg Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 milligram (mg) orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Overall Study STARTED	49	35
Overall Study Treated	48	35
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	49	35

Reasons for withdrawal

Measure	Cohort 1: Talazoparib 1 mg Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 milligram (mg) orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Overall Study Death	39	28
Overall Study Withdrawal by Subject	2	1
Overall Study Lost to Follow-up	4	1
Overall Study Study terminated by sponsor	4	5

Baseline Characteristics

A Phase 2, 2-Stage, 2-Cohort Study of Talazoparib (BMN 673), in Locally Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (ABRAZO Study)

Baseline characteristics by cohort

Measure	Cohort 1: Talazoparib 1 mg n=49 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Total n=84 Participants Total of all reporting groups
Age, Continuous	50.1 years STANDARD_DEVIATION 11.48 • n=5 Participants	53.4 years STANDARD_DEVIATION 11.05 • n=7 Participants	51.5 years STANDARD_DEVIATION 11.35 • n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants	34 Participants n=7 Participants	82 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until data cutoff date (01 Sep 2016)

Population: Tumor-evaluable population (TEP) included all treated participants who had a baseline and at least 1 post-baseline tumor assessment or who discontinued the study before first scheduled post-baseline tumor scan plus (+) 1 week window.

ORR: Percentage of participants with a confirmed best overall complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1). CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to less than (<) 10 millimeter (mm) in short axis. PR: Greater than or equal to (>=) 30 percent (%) decrease in sum of diameters of target lesions, compared to the sum at baseline. Response evaluation was done by an independent radiology facility (IRF).

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=48 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Objective Response Rate (ORR)	20.8 percentage of participants Interval 10.47 to 34.99	37.1 percentage of participants Interval 21.47 to 55.08

SECONDARY outcome

Timeframe: From randomization until data cutoff date (01 Sep 2016)

Population: TEP included all treated participants who had a baseline and at least 1 post-baseline tumor assessment or who discontinued the study before first scheduled post-baseline tumor scan + 1 week window.

CBR24: Percentage of participants with a best response of CR, PR or stable disease (SD) sustained for at least 24 weeks, as assessed by IRF using RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to <10 mm in short axis. PR: >=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. SD: Neither PR nor progression of disease (PD) criteria met. SD follow PR only when sum increases by less than 20% from the nadir, but previously seen 30% decrease from baseline no longer hold. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=48 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Clinical Benefit Rate-24 (CBR-24)	27.1 percentage of participants Interval 15.28 to 41.85	45.7 percentage of participants Interval 28.83 to 63.35

SECONDARY outcome

Timeframe: From first documentation of CR or PR until PD, last tumor assessment without PD before new anticancer treatment initiation or death due to any cause, whichever occurred first (up to the data cutoff date [01 Sep 2016])

Population: TEP included all treated participants who had a baseline and at least 1 post-baseline tumor assessment or who discontinued the study before first scheduled post-baseline tumor scan + 1 week window. Here 'Number of participants analyzed' signifies participants evaluable for this outcome measure.

DOR: Time from first documentation of CR or PR, to PD by IRF assessment using RECIST 1.1, or to death due to any cause, whichever occurred first. CR: Disappearance of all non-nodal target and non-target lesions, with target and non-target lymph nodes reduction to <10 mm in short axis. PR: >=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions. Participants with no PD or death at the analysis date were censored at last tumor assessment date prior to on or before initiation of a new anticancer therapy or before the data cutoff date.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=10 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=13 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Duration of Response (DOR)	5.8 months Interval 2.8 to Upper limit of 95% confidence interval was not reached due to insufficient number of events at the time of data cutoff (01 Sep 2016).	3.8 months Interval 2.8 to 10.1

SECONDARY outcome

Timeframe: From first dose of study drug until PD, last tumor assessment without PD before new anticancer treatment initiation or death due to any cause, whichever occurred first (up to the data cutoff date [01 Sep 2016])

Population: ITT population involved all enrolled participants including participants who were not treated.

PFS was defined as the time in months from the first dose of study drug to the first documentation of PD by investigator assessment using RECIST 1.1 or death on study due to any cause on or before the data cutoff date, whichever occurred first. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions. Participants with no PFS event at the analysis were censored at last tumor assessment date prior to data cutoff or date of new anticancer treatment initiation, whichever occurred first.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=49 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Progression Free Survival (PFS)	4.0 months Interval 2.8 to 5.4	5.6 months Interval 5.5 to 7.8

SECONDARY outcome

Timeframe: From first dose of study drug until death due to any cause (up to the data cutoff date [01 Sep 2016])

Population: ITT population involved all enrolled participants including participants who were not treated.

OS was defined as the time from first dose of study drug to death due to any cause. For participants without a death date at the time of data cutoff or permanently lost to follow-up, OS was right-censored at the date the participant was last known to be alive on or before the data cutoff date.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=49 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Overall Survival (OS)	11.8 months Interval 8.8 to 15.0	16.5 months Interval 10.1 to Upper limit of 95% confidence interval was not reached due to insufficient number of events at the time of data cutoff (01 Sep 2016).

SECONDARY outcome

Timeframe: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Population: Safety population included all participants who received at least 1 dose of talazoparib.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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; an important medical event or reaction, including events requiring medical intervention to prevent worsening to any of the previously noted seriousness criteria. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=48 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	47 Participants Interval 8.8 to 15.0	34 Participants Interval 10.1 to
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	16 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Population: Safety population included all participants who received at least 1 dose of talazoparib.

A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A treatment-related SAE was a treatment-related 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; an important medical event or reaction, including events requiring medical intervention to prevent worsening to any of the previously noted seriousness criteria. Related TEAEs are TEAEs that were judged by the investigators as possibly, probably, or definitely related to study drug. AEs included both SAES and non SAES.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=48 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	46 Participants	33 Participants
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	7 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Population: Safety population included all participants who received at least 1 dose of talazoparib.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Outcome of an AE was response to a question answered by the investigator: 'Is the AE leading to study discontinuation or death?' as 'yes'.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=48 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Number of Participants With Outcome in Response to Adverse Events (AEs) AEs leading to study drug discontinuation	4 Participants	1 Participants
Number of Participants With Outcome in Response to Adverse Events (AEs) AEs leading to death	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Population: Safety population included all participants who received at least 1 dose of talazoparib.

Laboratory tests included hematology (hemoglobin [low], leucocytes [low], lymphocytes [low], neutrophils [low], platelets [low]). Toxicity grades were evaluated based on national cancer institute- common terminology criteria for adverse events (NCI-CTCAE) version 4.03. Number of participants with increase of 2 or more CTCAE toxicity grades above baseline, for hematology laboratory parameter is reported in this outcome measure.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=48 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter) Hemoglobin (low)	19 Participants	16 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter) Leukocytes (low)	16 Participants	15 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter) Lymphocytes (low)	15 Participants	4 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter) Neutrophils (low)	20 Participants	17 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter) Platelets (low)	21 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after the last dose of study drug or before initiation of a new anticancer treatment, whichever occurred first (up to data cutoff date [01 Sep 2016])

Population: Safety population included all participants who received at least 1 dose of talazoparib.

Laboratory tests included serum chemistry (alanine aminotransferase [high], albumin [low], alkaline phosphatase [high], aspartate aminotransferase [high], bilirubin [high], calcium [low], glucose [high], magnesium [low], phosphate [low], potassium [high], potassium [low], sodium [high], sodium [low]). Toxicity grades were evaluated based on national cancer institute- common terminology criteria for adverse events (NCI-CTCAE) version 4.03. Number of participants with increase of 2 or more CTCAE toxicity grades above baseline, for chemistry laboratory parameter is reported in this outcome measure.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=48 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Alanine aminotransferase (high)	3 Participants	2 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Albumin (low)	3 Participants	0 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Alkaline phosphatase (high)	1 Participants	1 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Aspartate aminotransferase (high)	2 Participants	1 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Bilirubin (high)	2 Participants	0 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Calcium (low)	4 Participants	1 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Glucose (high)	1 Participants	1 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Magnesium (low)	1 Participants	0 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Phosphate (low)	6 Participants	2 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Potassium (high)	1 Participants	0 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Potassium (low)	2 Participants	0 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Sodium (high)	1 Participants	0 Participants
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) Sodium (low)	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Population: Safety population included all participants who received at least 1 dose of talazoparib.

Criteria for clinically significant vital signs changes: 1) Blood pressure: systolic blood pressure (SBP): greater than or equal to (>=30) millimeters of mercury (mmHg) increase from baseline, diastolic blood pressure (DBP): >=20 mmHg decrease from baseline; 2) Heart rate (HR): absolute HR greater than (>) 120 beats per minute (bpm) and >30 bpm increase from baseline, absolute HR less than (<) 50 bpm and >20 bpm decrease from baseline; 3) Weight: >10% decrease from baseline. Number of participants with any clinically significant change from baseline for blood pressure, heart rate and weight are reported in this outcome measure.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=48 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Blood pressure (SBP or DBP)	20 Participants	18 Participants
Number of Participants With Clinically Significant Change From Baseline in Vital Signs HR	2 Participants	0 Participants
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Weight	4 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Population: Safety population included all participants who received at least 1 dose of talazoparib.

Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=48 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Number of Participants With Clinically Significant Change From Baseline in Physical Findings	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Population: Safety population included all participants who received at least 1 dose of talazoparib.

Number of participants taking any non-study medications, therapies, including herbal supplements during the treatment-emergent period for the management of an adverse event or for the treatment of any other disease.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=48 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Number of Participants With At Least 1 Concomitant Medication	48 Participants	34 Participants

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycle 1, 2, 3, and 4 (data cutoff date: 01 Sep 2016)

Population: PK population included all participants who received at least 1 dose of talazoparib and had evaluable PK assessments. Here 'n' signifies participants evaluable for each specified categories.

Concentrations below the limit of quantitation values less than or equal to (<=) 25 picogram per milliliter (pg/mL) were set as zero. Pharmacokinetic (PK) analysis was not done separately for each reporting arm and cohorts were combined for PK analysis.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=83 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Trough Concentration Versus Time Summary of Talazoparib Day 1 of Cycle 1	10.3 pg/mL Standard Deviation 93.3	—
Trough Concentration Versus Time Summary of Talazoparib Day 1 of Cycle 2	4340 pg/mL Standard Deviation 2360	—
Trough Concentration Versus Time Summary of Talazoparib Day 1 of Cycle 3	4510 pg/mL Standard Deviation 2720	—
Trough Concentration Versus Time Summary of Talazoparib Day 1 of Cycle 4	3660 pg/mL Standard Deviation 1690	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to death, disease progression or end of treatment (30 days after last dose of study drug or before initiation of a new anticancer therapy, whichever occurred first [up to data cutoff date: 01 Sep 2016])

Population: ITT population involved all enrolled participants including participants who were not treated.

Time to deterioration was defined as the time from baseline to day to death, first occurrence of progression, or a >=10 point change from baseline in any of the functional status score and global health status/QOL score based on the EORTC-QLQ-C30, whichever occurred first. EORTC-QLQ-C30 questionnaire is a standardized instrument developed to assess the quality of life of people with cancer. EORTC-QLQ-C30 functional subscale includes 5 items: physical, role, emotional, cognitive, and social functioning. All of the single items of functional status subscale measures and global health status/QOL subscale range from 0 to 100, where higher scores represent a better level of functioning/quality of life.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=49 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Physical Functioning	3.1 months 95% Confidence Interval 15.84 • Interval 2.1 to 4.6	5.6 months 95% Confidence Interval 21.60 • Interval 5.3 to 7.7
Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Role Functioning	2.1 months 95% Confidence Interval 15.43 • Interval 1.4 to 2.8	4.2 months 95% Confidence Interval 31.67 • Interval 2.1 to 5.5
Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Emotional Functioning	2.7 months 95% Confidence Interval 19.29 • Interval 2.0 to 2.8	5.5 months 95% Confidence Interval 24.45 • Interval 4.3 to 5.6
Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Cognitive Functioning	2.7 months 95% Confidence Interval 21.36 • Interval 1.6 to 3.2	4.2 months 95% Confidence Interval 15.47 • Interval 2.8 to 5.5
Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Social Functioning	2.2 months 95% Confidence Interval 19.42 • Interval 1.4 to 2.9	5.3 months 95% Confidence Interval 23.57 • Interval 4.1 to 5.6
Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Global Health Status/QOL	2.8 months 95% Confidence Interval 18.33 • Interval 2.1 to 3.0	5.5 months 95% Confidence Interval 32.81 • Interval 4.2 to 5.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to death, disease progression or end of treatment (30 days after last dose of study drug or before initiation of a new anticancer therapy, whichever occurred first [up to data cutoff date: 01 Sep 2016])

Population: ITT population involved all enrolled participants including participants who were not treated.

Time to deterioration was defined as the time from baseline to day to death, first occurrence of progression, or a >=10 point change from baseline in any of the symptom score based on the EORTC-QLQ-BR23, whichever occurred first. EORTC-QLQ-BR23 is a disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer. EORTC-QLQ-BR23 symptoms subscale includes 4 items: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss. Each item is rated by choosing 1 of 4 possible responses that record the level of intensity (1= not at all, 2= a little, 3= quite a bit, and 4= very much) within each scale.

Outcome measures

Measure	Cohort 1: Talazoparib 1 mg n=49 Participants Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 Participants Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Time to Deterioration in Disease Specific Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23) Systemic Therapy Side Effects	2.8 months 95% Confidence Interval 5.69 • Interval 2.3 to 4.0	5.5 months 95% Confidence Interval 11.93 • Interval 4.1 to 5.6
Time to Deterioration in Disease Specific Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23) Breast Symptoms	3.1 months 95% Confidence Interval 9.71 • Interval 2.5 to 4.6	5.6 months 95% Confidence Interval 28.50 • Interval 5.3 to 7.7
Time to Deterioration in Disease Specific Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23) Arm Symptoms	2.6 months 95% Confidence Interval 8.27 • Interval 2.0 to 3.7	4.2 months 95% Confidence Interval 8.07 • Interval 2.8 to 5.5
Time to Deterioration in Disease Specific Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23) Upset by Hair Loss	4.0 months Interval 2.7 to 5.4	5.6 months Interval 5.3 to 7.7

Adverse Events

Cohort 1: Talazoparib 1 mg

Serious events: 16 serious events

Other events: 47 other events

Deaths: 0 deaths

Cohort 2: Talazoparib 1 mg

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cohort 1: Talazoparib 1 mg n=48 participants at risk Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 participants at risk Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Blood and lymphatic system disorders Anaemia	10.4% 5/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	2.9% 1/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Blood and lymphatic system disorders Thrombocytopenia	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	2.9% 1/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Blood and lymphatic system disorders Anaemia of malignant disease	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Oesophagitis	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Influenza	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	2.9% 1/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Neutropenic sepsis	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	2.9% 1/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Pneumonia	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Injury, poisoning and procedural complications Transfusion reaction	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Investigations Platelet count decreased	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	2.9% 1/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Metabolism and nutrition disorders Hypokalaemia	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Musculoskeletal and connective tissue disorders Arthralgia	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Silicon granuloma	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Nervous system disorders Central nervous system lesion	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Nervous system disorders Presyncope	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Nervous system disorders Syncope	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Psychiatric disorders Anxiety	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Atelectasis	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Surgical and medical procedures Lipoinjection	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Surgical and medical procedures Salpingo-oophorectomy	2.1% 1/47 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/34 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	2.9% 1/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.

Other adverse events

Measure	Cohort 1: Talazoparib 1 mg n=48 participants at risk Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Cohort 2: Talazoparib 1 mg n=35 participants at risk Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Blood and lymphatic system disorders Anaemia	47.9% 23/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	54.3% 19/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Blood and lymphatic system disorders Leukopenia	14.6% 7/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	17.1% 6/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Blood and lymphatic system disorders Lymphopenia	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	11.4% 4/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Blood and lymphatic system disorders Neutropenia	20.8% 10/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	34.3% 12/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Blood and lymphatic system disorders Thrombocytopenia	37.5% 18/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	25.7% 9/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Cardiac disorders Tachycardia	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Abdominal discomfort	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Abdominal distension	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Abdominal pain	14.6% 7/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	20.0% 7/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Abdominal pain upper	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	17.1% 6/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Constipation	18.8% 9/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	17.1% 6/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Diarrhoea	37.5% 18/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	28.6% 10/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Dry mouth	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Dyspepsia	10.4% 5/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Nausea	41.7% 20/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	42.9% 15/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Stomatitis	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	2.9% 1/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Toothache	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Gastrointestinal disorders Vomiting	20.8% 10/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	22.9% 8/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
General disorders Asthenia	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	28.6% 10/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
General disorders Axillary pain	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
General disorders Fatigue	60.4% 29/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	22.9% 8/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
General disorders Mucosal inflammation	8.3% 4/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
General disorders Non-cardiac chest pain	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
General disorders Oedema peripheral	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	17.1% 6/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
General disorders Pyrexia	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	14.3% 5/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Gingivitis	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Influenza	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	2.9% 1/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Lower respiratory tract infection	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Nasopharyngitis	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Pharyngitis	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Rhinitis	8.3% 4/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Sinusitis	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Upper respiratory tract infection	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	14.3% 5/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Investigations Alanine aminotransferase increased	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Investigations Aspartate aminotransferase increased	8.3% 4/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Investigations Neutrophil count decreased	10.4% 5/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	14.3% 5/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Investigations Platelet count decreased	14.6% 7/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	14.3% 5/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Investigations Weight decreased	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Investigations White blood cell count decreased	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	14.3% 5/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Metabolism and nutrition disorders Decreased appetite	25.0% 12/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	28.6% 10/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Metabolism and nutrition disorders Hyperglycaemia	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Metabolism and nutrition disorders Hypomagnesaemia	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	0.00% 0/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Metabolism and nutrition disorders Hyponatraemia	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 8/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	25.7% 9/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Musculoskeletal and connective tissue disorders Back pain	25.0% 12/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	22.9% 8/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Musculoskeletal and connective tissue disorders Muscle spasms	8.3% 4/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	14.3% 5/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Musculoskeletal and connective tissue disorders Neck pain	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Musculoskeletal and connective tissue disorders Pain in extremity	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Nervous system disorders Dizziness	12.5% 6/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Nervous system disorders Dysgeusia	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Nervous system disorders Headache	18.8% 9/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	31.4% 11/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Nervous system disorders Neuralgia	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Nervous system disorders Neuropathy peripheral	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	11.4% 4/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Psychiatric disorders Depression	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Psychiatric disorders Insomnia	10.4% 5/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Cough	18.8% 9/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	20.0% 7/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.8% 9/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	25.7% 9/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Skin and subcutaneous tissue disorders Alopecia	22.9% 11/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	17.1% 6/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Skin and subcutaneous tissue disorders Dry skin	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	11.4% 4/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Skin and subcutaneous tissue disorders Pruritus	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Vascular disorders Hot flush	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Vascular disorders Lymphoedema	6.2% 3/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
General disorders Chills	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Oral herpes	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Infections and infestations Viral upper respiratory tract infection	22.9% 11/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Musculoskeletal and connective tissue disorders Myalgia	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Nervous system disorders Presyncope	0.00% 0/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Psychiatric disorders Anxiety	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.2% 2/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	8.6% 3/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.
Skin and subcutaneous tissue disorders Hyperhidrosis	2.1% 1/48 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.	5.7% 2/35 • Baseline up to end of study (up to maximum duration of 42.8 months) 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. AEs and SAEs were collected for safety population.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER