Trial Outcomes & Findings for A Bioequivalence Study Between the Proposed and Current Talazoparib Capsule Formulation and Food Effect Study for the Proposed Talazoparib Capsule Formulation in Participants With Advanced Solid Tumors (NCT NCT04672460)

NCT ID: NCT04672460

Last Updated: 2024-09-25

Results Overview

AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 73 participants
• Primary outcome timeframe: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.
• Results posted on: 2024-09-25

Participant Flow

A total of 73 participants were assigned to study treatment, and all of them were permanently discontinued from study treatment. Fifty-two participants entered the safety follow-up phase and 46 of them completed the safety follow-up.

Participant milestones

Measure	Sequence 1 Participants were randomly assigned to sequence BAC. Participants received treatment B: talazoparib soft gel capsule formulation 1 mg once daily given under fasting condition in Period 1 for 28 days followed by Treatment A: current commercial talazoparib formulation 1 mg once daily given under fasting condition in Period 2 for 21 days. Participants received Treatment C: talazoparib soft gelatin capsule formulation 1 mg once daily given with food in Period 3 (food effect assessment) for 21 days. Participants who required a dose reduction, had unstable renal function, experienced renal function worsening to moderate/severe renal impairment during the study, or completed the food effect assessment, were enrolled over to the maintenance phase which consisted of repeating 28- day cycles of treatment with the current commercial talazoparib formulation 1 mg once daily.	Sequence 2 Participants were randomly assigned to sequence ABC. Participants received treatment A: current commercial talazoparib formulation 1 mg once daily given under fasting condition in Period 1 for 28 days followed by Treatment B: talazoparib soft gel capsule formulation 1 mg once daily given under fasting condition in Period 2 for 21 days. Participants received Treatment C: talazoparib soft gelatin capsule formulation 1 mg once daily given with food in Period 3 (food effect assessment) for 21 days. Participants who required a dose reduction, had unstable renal function, experienced renal function worsening to moderate/severe renal impairment during the study, or completed the food effect assessment, were enrolled over to the maintenance phase which consisted of repeating 28- day cycles of treatment with the current commercial talazoparib formulation 1 mg once daily.
Bioequivalence Phase: Period 1 (28 Days) STARTED	35	38
Bioequivalence Phase: Period 1 (28 Days) COMPLETED	28	28
Bioequivalence Phase: Period 1 (28 Days) NOT COMPLETED	7	10
Bioequivalence Phase: Period 2 (21 Days) STARTED	27	25
Bioequivalence Phase: Period 2 (21 Days) COMPLETED	25	20
Bioequivalence Phase: Period 2 (21 Days) NOT COMPLETED	2	5
Food Effect Phase: Period 3 (21 Days) STARTED	16	14
Food Effect Phase: Period 3 (21 Days) COMPLETED	11	11
Food Effect Phase: Period 3 (21 Days) NOT COMPLETED	5	3
Maintenance Phase: Period 4 (28 Days) STARTED	21	20
Maintenance Phase: Period 4 (28 Days) COMPLETED	0	0
Maintenance Phase: Period 4 (28 Days) NOT COMPLETED	21	20

Reasons for withdrawal

Measure	Sequence 1 Participants were randomly assigned to sequence BAC. Participants received treatment B: talazoparib soft gel capsule formulation 1 mg once daily given under fasting condition in Period 1 for 28 days followed by Treatment A: current commercial talazoparib formulation 1 mg once daily given under fasting condition in Period 2 for 21 days. Participants received Treatment C: talazoparib soft gelatin capsule formulation 1 mg once daily given with food in Period 3 (food effect assessment) for 21 days. Participants who required a dose reduction, had unstable renal function, experienced renal function worsening to moderate/severe renal impairment during the study, or completed the food effect assessment, were enrolled over to the maintenance phase which consisted of repeating 28- day cycles of treatment with the current commercial talazoparib formulation 1 mg once daily.	Sequence 2 Participants were randomly assigned to sequence ABC. Participants received treatment A: current commercial talazoparib formulation 1 mg once daily given under fasting condition in Period 1 for 28 days followed by Treatment B: talazoparib soft gel capsule formulation 1 mg once daily given under fasting condition in Period 2 for 21 days. Participants received Treatment C: talazoparib soft gelatin capsule formulation 1 mg once daily given with food in Period 3 (food effect assessment) for 21 days. Participants who required a dose reduction, had unstable renal function, experienced renal function worsening to moderate/severe renal impairment during the study, or completed the food effect assessment, were enrolled over to the maintenance phase which consisted of repeating 28- day cycles of treatment with the current commercial talazoparib formulation 1 mg once daily.
Bioequivalence Phase: Period 1 (28 Days) Death	1	2
Bioequivalence Phase: Period 1 (28 Days) Progressive disease	2	4
Bioequivalence Phase: Period 1 (28 Days) Withdrawal by Subject	0	3
Bioequivalence Phase: Period 1 (28 Days) Global deterioration of health status	0	1
Bioequivalence Phase: Period 1 (28 Days) Adverse Event	3	0
Bioequivalence Phase: Period 1 (28 Days) Other	1	0
Bioequivalence Phase: Period 2 (21 Days) Progressive disease	1	5
Bioequivalence Phase: Period 2 (21 Days) Withdrawal by Subject	1	0
Food Effect Phase: Period 3 (21 Days) Adverse Event	1	0
Food Effect Phase: Period 3 (21 Days) Progressive disease	3	1
Food Effect Phase: Period 3 (21 Days) Withdrawal by Subject	0	1
Food Effect Phase: Period 3 (21 Days) Refused further treatment	0	1
Food Effect Phase: Period 3 (21 Days) Other	1	0
Maintenance Phase: Period 4 (28 Days) Adverse Event	1	0
Maintenance Phase: Period 4 (28 Days) Progressive disease	10	12
Maintenance Phase: Period 4 (28 Days) Refused further treatment	1	0
Maintenance Phase: Period 4 (28 Days) Other	9	8

Baseline Characteristics

A Bioequivalence Study Between the Proposed and Current Talazoparib Capsule Formulation and Food Effect Study for the Proposed Talazoparib Capsule Formulation in Participants With Advanced Solid Tumors

Baseline characteristics by cohort

Measure	All Participants n=73 Participants Participants were randomly assigned to 1 of 2 sequences to receive treatments A, B and C in different order with 3 periods. The first 2 periods were for BE assessment with treatment A and B (Period 1 was 28 days and Period 2 was 21 days); Period 3 was a 21-day period to evaluate the food effect with treatment C. Sequence 1 (Period 1: Treatment B; Period 2: Treatment A; Period 3: Treatment C); Sequence 2 (Period 1: Treatment A; Period 2: Treatment B; Period 3: Treatment C); Treatment A: current commercial talazoparib formulation 1 mg once daily given under fasting condition (reference for BE evaluation); Treatment B: the proposed talazoparib soft gel capsule formulation 1 mg once daily given under fasting condition (test for BE evaluation, reference for food effect evaluation); Treatment C: the proposed talazoparib soft gelatin capsule formulation 1 mg once daily given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).
Age, Continuous	56.8 Years STANDARD_DEVIATION 9.18 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	63 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race/Ethnicity, Customized White	57 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	11 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Not reported	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

Population: The analysis population was defined as all participants randomized and treated who had primary PK parameter of AUC24 or Cmax in at least 1 treatment period.

AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

Outcome measures

Measure	Treatment A: Commercial Capsule Fast n=47 Participants Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=40 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of Talazoparib After Multiple Dosing Under Fasted Conditions	178.7 nanograms*hour/millilitre (ng*hr/mL) Geometric Coefficient of Variation 40	173.0 nanograms*hour/millilitre (ng*hr/mL) Geometric Coefficient of Variation 32	—	—

PRIMARY outcome

Timeframe: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

Population: The analysis population was defined as all participants randomized and treated who had primary PK parameter of AUC24 or Cmax in at least 1 treatment period.

Cmax was the maximum observed plasma concentration and was directly observed from data. The geometric coefficient of variation was expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

Outcome measures

Measure	Treatment A: Commercial Capsule Fast n=47 Participants Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=40 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Maximum Observed Plasma Concentration (Cmax) of Talazoparib After Multiple Dosing Under Fasted Conditions	14.95 nanograms/millilitre (ng/mL) Geometric Coefficient of Variation 40	19.19 nanograms/millilitre (ng/mL) Geometric Coefficient of Variation 32	—	—

PRIMARY outcome

Timeframe: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

Population: The analysis population was defined as all participants randomized and treated who had primary PK parameter of AUC24 or Cmax in at least 1 treatment period.

AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

Outcome measures

Measure	Treatment A: Commercial Capsule Fast n=40 Participants Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=21 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of Talazoparib After Multiple Dosing Under Fed Conditions	173.0 ng*hr/mL Geometric Coefficient of Variation 32	151.3 ng*hr/mL Geometric Coefficient of Variation 38	—	—

PRIMARY outcome

Timeframe: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

Population: The analysis population was defined as all participants randomized and treated who had primary PK parameter of AUC24 or Cmax in at least 1 treatment period. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Cmax was the maximum observed plasma concentration and was directly observed from data. The geometric coefficient of variation was expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

Outcome measures

Measure	Treatment A: Commercial Capsule Fast n=40 Participants Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=22 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Maximum Observed Plasma Concentration (Cmax) of Talazoparib After Multiple Dosing Under Fed Conditions	19.19 ng/mL Geometric Coefficient of Variation 32	11.36 ng/mL Geometric Coefficient of Variation 38	—	—

SECONDARY outcome

Timeframe: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

Population: The analysis population was defined as all participants randomized and treated who had primary PK parameter of AUC24 or Cmax in at least 1 treatment period.

Apparent Clearance After Oral Dose (CL/F) was defined as apparent clearance after oral dose on the last day of treatment period. The geometric coefficient of variation is expressed in percentage.

Outcome measures

Measure	Treatment A: Commercial Capsule Fast n=47 Participants Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=40 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed n=21 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Apparent Clearance After Oral Dose (CL/F) of Talazoparib After Multiple Dosing	5.631 liter per hour (L/hr) Geometric Coefficient of Variation 40	5.808 liter per hour (L/hr) Geometric Coefficient of Variation 32	6.648 liter per hour (L/hr) Geometric Coefficient of Variation 38	—

SECONDARY outcome

Timeframe: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

Population: The analysis population was defined as all participants randomized and treated who had primary PK parameter of AUC24 or Cmax in at least 1 treatment period. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Tmax was defined as time to reach maximum observed plasma concentration.

Outcome measures

Measure	Treatment A: Commercial Capsule Fast n=47 Participants Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=40 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed n=22 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Time of Observed Maximum Plasma Concentration (Tmax) of Talazoparib After Multiple Dosing	2.00 hour Interval 0.5 to 6.0	0.975 hour Interval 0.417 to 4.0	4.00 hour Interval 0.967 to 24.7	—

SECONDARY outcome

Timeframe: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

Population: The analysis population was defined as all participants randomized and treated who had primary PK parameter of AUC24 or Cmax in at least 1 treatment period.

AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation was expressed in percentage.

Outcome measures

Measure	Treatment A: Commercial Capsule Fast n=47 Participants Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=40 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed n=21 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Area Under the Plasma Concentration-Time Profile From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of Talazoparib After Multiple Dosing	178.5 ng*hr/mL Geometric Coefficient of Variation 41	173.4 ng*hr/mL Geometric Coefficient of Variation 33	152.1 ng*hr/mL Geometric Coefficient of Variation 38	—

SECONDARY outcome

Timeframe: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2, predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

Population: The analysis population was defined as all participants randomized and treated who had primary PK parameter of AUC24 or Cmax in at least 1 treatment period. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Ctrough was the pre-dose concentration during multiple dosing and was directly observed from data. The geometric coefficient of variation is expressed in percentage.

Outcome measures

Measure	Treatment A: Commercial Capsule Fast n=47 Participants Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=40 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed n=22 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Predose Concentration During Multiple Dosing (Ctrough) of Talazoparib After Multiple Dosing	4.269 ng/mL Geometric Coefficient of Variation 48	3.645 ng/mL Geometric Coefficient of Variation 44	3.633 ng/mL Geometric Coefficient of Variation 60	—

SECONDARY outcome

Timeframe: Day 1 up to 28 days after last dose of study drug (maximum up to 388 days)

Population: Population analysis set included all participants randomly assigned to investigational product (IP) and who took at least 1 dose of IP.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason.

Outcome measures

Measure	Treatment A: Commercial Capsule Fast n=65 Participants Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=60 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed n=30 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance n=41 Participants Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) Participants with adverse events	42 Participants	36 Participants	15 Participants	31 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) Participants with serious adverse events	9 Participants	7 Participants	1 Participants	7 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) Participants with Maximum Grade 3 or 4 adverse events	13 Participants	10 Participants	5 Participants	12 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) Participants with Maximum Grade 5 adverse events	3 Participants	4 Participants	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) Participants discontinued study drug due to adverse events	3 Participants	4 Participants	1 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) Participants with dose reduced or temporary discontinuation due to adverse events	13 Participants	9 Participants	6 Participants	13 Participants

SECONDARY outcome

Timeframe: Day 1 up to 28 days after last dose of study drug (maximum up to 388 days)

Population: Population analysis set included all participants randomly assigned to IP and who took at least 1 dose of IP.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason.

Outcome measures

Measure	Treatment A: Commercial Capsule Fast n=65 Participants Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=60 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed n=30 Participants The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance n=41 Participants Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Treatment Related) Participants with adverse events	22 Participants	26 Participants	11 Participants	16 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Treatment Related) Participants with serious adverse events	2 Participants	0 Participants	0 Participants	3 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Treatment Related) Participants with Maximum Grade 3 or 4 adverse events	9 Participants	8 Participants	4 Participants	10 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Treatment Related) Participants discontinued study drug due to adverse events	1 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Treatment Related) Participants with dose reduced or temporary discontinuation due to adverse events	9 Participants	7 Participants	6 Participants	12 Participants

Adverse Events

Treatment A: Commercial Capsule Fast

Serious events: 9 serious events

Other events: 25 other events

Deaths: 4 deaths

Treatment B: Soft Gel Capsule Fast

Serious events: 7 serious events

Other events: 25 other events

Deaths: 5 deaths

Treatment C: Soft Gel Capsule Fed

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Maintenance

Serious events: 7 serious events

Other events: 20 other events

Deaths: 1 deaths

Serious adverse events

Measure	Treatment A: Commercial Capsule Fast n=65 participants at risk Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=60 participants at risk The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed n=30 participants at risk The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance n=41 participants at risk Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Blood and lymphatic system disorders Anaemia	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	4.9% 2/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Blood and lymphatic system disorders Thrombocytopenia	3.1% 2/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Cardiac disorders Atrial fibrillation	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Ascites	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Dysphagia	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Intestinal obstruction	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	4.9% 2/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Intestinal perforation	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Nausea	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Small intestinal obstruction	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
General disorders Disease progression	3.1% 2/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.0% 3/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
General disorders Fatigue	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Hepatobiliary disorders Biliary obstruction	3.1% 2/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Hepatobiliary disorders Hepatic failure	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Liver abscess	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Pneumonia	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Sepsis	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Septic shock	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Nervous system disorders Aphasia	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Nervous system disorders Headache	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Nervous system disorders Spinal cord compression	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.3% 1/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Vascular disorders Hypotension	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Vascular disorders Iliac artery occlusion	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.

Other adverse events

Measure	Treatment A: Commercial Capsule Fast n=65 participants at risk Current commercial talazoparib formulation 1 mg once daily was given under fasted conditions (reference for BE evaluation).	Treatment B: Soft Gel Capsule Fast n=60 participants at risk The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given under fasted conditions (test for BE evaluation, reference for food-effect evaluation).	Treatment C: Soft Gel Capsule Fed n=30 participants at risk The proposed talazoparib soft gelatin capsule formulation 1 mg once daily was given with food (on the PK sampling day, high-fat/high-calorie meal was administered in the clinical sites prior to the administration of the proposed talazoparib soft gelatin capsule formulation; test for food-effect evaluation).	Maintenance n=41 participants at risk Participants who had repeated a period 2 times but still could not meet PK evaluable criteria, needed a dose reduction, had unstable renal function, had experienced renal function worsening to moderate/severe renal impairment during the study, or had completed the food effect assessment, was rolled over to the maintenance phase which consisted of repeating 28 day cycles of treatment with the current commercial formulation.
Blood and lymphatic system disorders Anaemia	10.8% 7/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	13.3% 8/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	16.7% 5/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	26.8% 11/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Blood and lymphatic system disorders Neutropenia	4.6% 3/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.3% 2/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.3% 1/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.3% 3/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Abdominal pain	6.2% 4/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.0% 3/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.7% 2/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Diarrhoea	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.7% 4/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.3% 1/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.3% 3/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Nausea	10.8% 7/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	8.3% 5/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.3% 1/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Vomiting	4.6% 3/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.7% 2/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	4.9% 2/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
General disorders Fatigue	6.2% 4/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	18.3% 11/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.7% 2/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	17.1% 7/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Investigations Aspartate aminotransferase increased	6.2% 4/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Investigations Platelet count decreased	6.2% 4/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.7% 4/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.3% 3/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Metabolism and nutrition disorders Decreased appetite	7.7% 5/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	8.3% 5/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.4% 1/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Renal and urinary disorders Haematuria	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.3% 3/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Skin and subcutaneous tissue disorders Alopecia	3.1% 2/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.7% 2/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	12.2% 5/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Back pain	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.3% 1/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.3% 3/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Muscle spasms	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.3% 3/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Vascular disorders Hypotension	1.5% 1/65 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/60 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/30 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.3% 3/41 • From day 1 up to maximum 388 days. The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.

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