Open-Label Extension and Safety Study of Talazoparib

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Study arms

• Experimental
  Talazoparib

  Drug: Talazoparib

Interventions

• DrugTalazoparib

  Maximum starting dose: 1mg/day or last tolerated dose in the originating protocol

  Also known as: MDV3800

Primary outcomes

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs

   An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. SAE was any untoward medical occurrence that at any dose resulted in death; inpatient hospitalization or prolongation of existing hospitalization; was life-threatening (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect or was considered as an important medical event. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. AE included both SAEs and all non-SAEs. Treatment-related TEAEs were defined as any TEAE with at least a possible relationship to the study drug as assessed by the investigator or that was missing the assessment of causal relationship whose relationship to the study drug could not be ruled out.

   Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

2. Number of Participants With Grade 3 or 4 TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4

   An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Severity was graded using NCI-CTCAE version 4 where, Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. Number of participants with Grade 3 or 4 TEAEs were reported.

   Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

3. Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death

   An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Number of participants with TEAEs leading to dose reduction, permanent study drug discontinuation and death were reported.

   Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

4. Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests

   The following liver parameters were analyzed: aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin (TBL) and alkaline phosphatase (ALP). The criteria for clinically significant abnormalities for liver parameters included AST or ALT greater than or equal to (\>=) 3 times upper limit of normal (ULN); ALT or AST greater than (\>) 5 times ULN; ALT or AST \> 10 times ULN; ALT or AST \> 20 times ULN; total TBL \>2 times ULN; ALT or AST \>= 3 times ULN and TBL \> 2 times ULN and ALT or AST \>= 3 times ULN and TBL \> 2 times ULN and ALP \< 2 times ULN.

   Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

5. Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters

   The following hematology parameters were analyzed: hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 and 4 toxicities were reported. Low indicates values lower than the normal range.

   Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

6. Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters

   The following chemistry parameters were analyzed: alkaline phosphatase, bilirubin and creatinine. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 or 4 toxicities were reported. High indicates values higher than the normal range.

   Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

7. Number of Participants With Clinically Significant Changes in Vital Signs and Weight

   Criteria for clinically significant changes in vital signs included a) Systolic blood pressure (SBP): 1) absolute results \>180 millimeter of mercury (mmHg) and increase from baseline \>=40 mmHg, 2) absolute results \<90 mmHg and decrease from baseline \>30 mmHg; b) Diastolic blood pressure (DBP): 1) absolute results \>110 mmHg and increase from baseline \>=30 mmHg , 2) absolute results \<50 mmHg and decrease from baseline \>20 mmHg , 3) increase from baseline \>=20 mmHg; c) Heart rate: 1) absolute results \>120 beats per minute (bpm) and increase from baseline \>30 bpm, 2) absolute results \<50 bpm and \>20 bpm decrease from baseline; d) Temperature: \<=34.5 or \>=38 degree Celsius. Criteria for clinically significant changes in weight: \>10 percent (%) decrease from baseline.

   Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

Baseline characteristics

Study documents

• Study protocol · Nov 14, 2018
• Statistical analysis plan · Jun 15, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.