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This is a Phase 1 study which consists of 2 parts; Dose Escalation part and Expansion part.
The dose escalation part is open-label, and evaluates safety, preliminary efficacy and PK of single-agent talazoparib in sequential cohorts of adult patients with advanced solid tumors who are resistant to standard therapy or for whom no standard therapy is available.
In the dose escalation part, up to 18 (minimum 3) patients are expected to be enrolled depending on the observed DLTs.
The expansion part is designed to assess the efficacy, safety and PK of single-agent talazoparib at RP2D determined in the dose escalation part in adult patients with locally advanced or metastatic breast cancer who have deleterious or suspected deleterious germline BRCA1 or BRCA2 mutations.
In the expansion part, a minimum of 17 patients will be enrolled evaluable for the primary endpoint.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| talazoparib | Experimental | 0.75 mg/day or 1.0 mg/day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| talazoparib | Drug | Talazoparib will be administered orally on a continuous basis. Talazoparib may be taken with or without food. Each cycle will consist of 28 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT) | DLT was defined as any of the following adverse events occurred in 1st treatment cycle and attributable to talazoparib: hematologic- grade(G) 4 neutropenia greater than (>)7days; Febrile neutropenia >1 hour; G greater than or equal to (>=)3 neutropenic infection, thrombocytopenia associated with G2 hemorrhage; G4 thrombocytopenia, anemia; G3 anemia required transfusion; daily dosing interrupted for >=7 total days in first cycle for G3 neutropenia/thrombocytopenia. Non-hematologic: any G>=3AE except non-clinically significant laboratory abnormalities, Non-hematologic AE deemed not clinically significant, nausea, vomiting, diarrhea responded to medical intervention within 72 hours, fatigue improved to G>=2 within 7 days. Alanine/aspartate aminotransferase (ALT/AST)>5*upper limit of normal(ULN) and 2*increases above baseline values; ALT/AST>=3*ULN concurrent with total bilirubin (TB)>2*ULN; TB>5*ULN; failure to deliver 75percent(%) of doses due to toxicities attributable to talazoparib. | Cycle 1 (28 days) |
| Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment | Confirmed OR in participants was defined as the percentage of participants with complete response (CR) or partial response (PR) as best response determined by investigator as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. |
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[Dose Escalation Part]
Inclusion Criteria:
Exclusion Criteria:
[Dose Expansion Part]
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aichi Cancer Center Hospital | Nagoya | Aichi-ken | 464-8681 | Japan | ||
| National Cancer Center Hospital East |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35907135 | Derived | Kotani H, Masuda N, Yamashita T, Naito Y, Taira T, Inoue K, Takahashi M, Yonemori K, Toyoizumi S, Mori Y, Nagasawa T, Hori N, Iwata H. Efficacy and safety of talazoparib in Japanese patients with germline BRCA-mutated locally advanced or metastatic breast cancer: results of the phase 1 dose-expansion study. Breast Cancer. 2022 Nov;29(6):1088-1098. doi: 10.1007/s12282-022-01390-w. Epub 2022 Jul 30. | |
| 34160752 |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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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.
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Dose escalation period: total 9 participants were screened, enrolled into the study and assigned to study treatment. Dose expansion period: total 22 participants were screened, out of which 3 participants were screen failure. 19 participants actually enrolled into the study and assigned to study treatment. Data reported based on the primary completion date of 11 January 2021.
This study included 2 periods: dose escalation and dose expansion. The recommended dose for dose expansion period of talazoparib was determined in dose escalation period.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Escalation: Talazoparib 0.75 mg | Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 milligrams (mg) orally, once daily (QD) in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day minus (-) 7. |
| FG001 | Dose Escalation: Talazoparib 1.0 mg | Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7. |
| FG002 | Dose Expansion: Talazoparib 1.0 mg | Participants with Germline breast cancer susceptibility gene mutation (gBRCAm) HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose Escalation Period (Up to 286 Days) |
|
| |||||||||||||||||||||
| Dose Expansion Period (Up to 502 Days) |
|
Full analysis set (FAS) included all participants assigned to study treatment and who took at least 1 dose of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Escalation: Talazoparib 0.75 mg | Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT) | DLT was defined as any of the following adverse events occurred in 1st treatment cycle and attributable to talazoparib: hematologic- grade(G) 4 neutropenia greater than (>)7days; Febrile neutropenia >1 hour; G greater than or equal to (>=)3 neutropenic infection, thrombocytopenia associated with G2 hemorrhage; G4 thrombocytopenia, anemia; G3 anemia required transfusion; daily dosing interrupted for >=7 total days in first cycle for G3 neutropenia/thrombocytopenia. Non-hematologic: any G>=3AE except non-clinically significant laboratory abnormalities, Non-hematologic AE deemed not clinically significant, nausea, vomiting, diarrhea responded to medical intervention within 72 hours, fatigue improved to G>=2 within 7 days. Alanine/aspartate aminotransferase (ALT/AST)>5*upper limit of normal(ULN) and 2*increases above baseline values; ALT/AST>=3*ULN concurrent with total bilirubin (TB)>2*ULN; TB>5*ULN; failure to deliver 75percent(%) of doses due to toxicities attributable to talazoparib. | The per-protocol analysis set included all enrolled participants who received at least 1 dose of study treatment and who did not have major treatment deviations during the first cycle. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period. | Posted | Count of Participants | Participants | Cycle 1 (28 days) |
Dose escalation: maximum duration up to 286 days; Dose expansion: maximum duration up to 502 days
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety set was evaluated.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Escalation: Talazoparib 0.75 mg | Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Brain cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v23.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 28, 2019 | Dec 20, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 15, 2021 | Dec 20, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C586365 | talazoparib |
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| From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days) |
| Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. AE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Relatedness to study drug was assessed by the investigator. | From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days) |
| Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with grade 3 or higher AEs were reported. | From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days) |
| Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure. | Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days |
| Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Hematological parameters included: Anemia, Hemoglobin increased, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure. | Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days |
| Dose Escalation: Number of Participants With Abnormalities in Vital Signs | Vital sign abnormalities: a) Sitting systolic blood pressure: <90 millimeter of mercury (mmHg), decrease from baseline >=30 mmHg, increase from baseline >=30 mmHg; b) Sitting diastolic blood pressure: minimum <50 mmHg, decrease from baseline >=20 mmHg, increase from baseline >=20 mmHg; c) Sitting pulse rate: minimum <40 beats per minute (bpm), maximum >120 bpm. Only those categories in which at least one participant had data were reported in this outcome measure. | Baseline up to 286 days |
| Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib | Cmax was defined as the maximum observed plasma concentration of talazoparib. | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
| Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
| Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib | Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast). | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
| Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib | Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours. | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day -7 of Cycle 1 |
| Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F) | Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
| Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
| Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib | Terminal half-life (t1/2) is the time measured for the plasma concentration of a drug to decrease by half of its initial concentration. | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
| Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre dose) to extrapolated infinite time (0-inf). | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
| Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib | Css,max is maximum observed plasma concentration at steady state (post multiple dose) of Talazoparib. | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 |
| Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib | Pre dose plasma concentration of talazoparib. | Pre dose on Day 22 of Cycle 1 |
| Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib | Tss,max = Time to reach Cmax for talazoparib at steady state (post multiple dose). | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 |
| Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib | Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau) at steady state (post multiple dose), where dosing interval was 24 hours. | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 |
| Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss) | Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 |
| Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib | Accumulation ratio for AUC was calculated as AUCtau for Day 22 divided by AUCtau for Day -7, where AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours. | Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day -7 and Day 22 of Cycle 1 |
| Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib | Rss was calculated by dividing AUCtau at steady state (post multiple dosing on Day 22) by single dose AUCinf (on Day -7). AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours. AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1; Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 |
| Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | OR in participants was defined as the percentage of participants with CR or PR as best response determined by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 286 days) |
| Dose Escalation: Progression Free Survival (PFS) | PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. | From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 286 days) |
| Dose Escalation: Duration of Response (DOR) | DOR was defined as the time between the date of the first documented objective response (PR or CR) and the date of the first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. | From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 286 days) |
| Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | Confirmed OR in participants was defined as the percentage of participants with CR or PR as best response determined by BICR as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) |
| Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. | Baseline up to Week 16, Baseline up to Week 24 |
| Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by BICR as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. | Baseline up to Week 16, Baseline up to Week 24 |
| Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days) |
| Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by BICR according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days) |
| Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. | From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) |
| Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. | From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) |
| Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. | From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days) |
| Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. | From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days) |
| Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12 | OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at Month 12. Probability of participants who were event free at Month 12 was estimated by Kaplan-Meier method and reported. | At Month 12 |
| Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib | Pre dose plasma drug concentration. | Pre dose at 0 hour on Day 1 of Cycle 2, 3, 4 and unplanned (any time during dose expansion period up to 502 days) |
| Kashiwa |
| Chiba |
| 277-8577 |
| Japan |
| National Hospital Organization Hokkaido Cancer Center | Sapporo | Hokkaido | 003-0804 | Japan |
| Kanagawa Cancer Center | Yokohama | Kanagawa | 241-8515 | Japan |
| Saitama Cancer Center | Kitaadachi-gun | Saitama | 362-0806 | Japan |
| National Cancer Center Hospital | Chuo-Ku | Tokyo | 104-0045 | Japan |
| Hakuaikai Medical Corporation Sagara Hospital | Kagoshima | 892-0833 | Japan |
| National Hospital Organization Osaka National Hospital | Osaka | 540-0006 | Japan |
| Derived |
| Naito Y, Kuboki Y, Ikeda M, Harano K, Matsubara N, Toyoizumi S, Mori Y, Hori N, Nagasawa T, Kogawa T. Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study. Invest New Drugs. 2021 Dec;39(6):1568-1576. doi: 10.1007/s10637-021-01120-7. Epub 2021 Jun 23. |
| NOT COMPLETED |
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| BG001 | Dose Escalation: Talazoparib 1.0 mg | Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7. |
| BG002 | Dose Expansion: Talazoparib 1.0 mg | Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days). |
| BG003 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Primary | Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment | Confirmed OR in participants was defined as the percentage of participants with complete response (CR) or partial response (PR) as best response determined by investigator as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Number | 90% Confidence Interval | Percentage of participants | From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. | The safety analysis set (SAS) included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Count of Participants | Participants | From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days) |
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| Secondary | Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. AE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Relatedness to study drug was assessed by the investigator. | The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Count of Participants | Participants | From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days) |
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| Secondary | Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with grade 3 or higher AEs were reported. | The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Count of Participants | Participants | From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days) |
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| Secondary | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure. | The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Count of Participants | Participants | Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days |
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| Secondary | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Hematological parameters included: Anemia, Hemoglobin increased, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure. | The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Count of Participants | Participants | Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days |
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| Secondary | Dose Escalation: Number of Participants With Abnormalities in Vital Signs | Vital sign abnormalities: a) Sitting systolic blood pressure: <90 millimeter of mercury (mmHg), decrease from baseline >=30 mmHg, increase from baseline >=30 mmHg; b) Sitting diastolic blood pressure: minimum <50 mmHg, decrease from baseline >=20 mmHg, increase from baseline >=20 mmHg; c) Sitting pulse rate: minimum <40 beats per minute (bpm), maximum >120 bpm. Only those categories in which at least one participant had data were reported in this outcome measure. | The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Count of Participants | Participants | Baseline up to 286 days |
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| Secondary | Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib | Cmax was defined as the maximum observed plasma concentration of talazoparib. | The Pharmacokinetic (PK) parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
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| Secondary | Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Median | Full Range | Hours | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
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| Secondary | Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib | Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast). | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram hour per milliliter | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
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| Secondary | Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib | Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours. | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram hour per milliliter | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day -7 of Cycle 1 |
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| Secondary | Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F) | Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here "overall number of participants analyzed" signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
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| Secondary | Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here "overall number of participants analyzed" signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
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| Secondary | Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib | Terminal half-life (t1/2) is the time measured for the plasma concentration of a drug to decrease by half of its initial concentration. | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here "overall number of participants analyzed" signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Mean | Standard Deviation | Hours | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
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| Secondary | Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre dose) to extrapolated infinite time (0-inf). | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here "overall number of participants analyzed" signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram hour per milliliter | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 |
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| Secondary | Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib | Css,max is maximum observed plasma concentration at steady state (post multiple dose) of Talazoparib. | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 |
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| Secondary | Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib | Pre dose plasma concentration of talazoparib. | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | Pre dose on Day 22 of Cycle 1 |
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| Secondary | Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib | Tss,max = Time to reach Cmax for talazoparib at steady state (post multiple dose). | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Median | Full Range | Hours | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 |
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| Secondary | Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib | Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau) at steady state (post multiple dose), where dosing interval was 24 hours. | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram hour per milliliter | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 |
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| Secondary | Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss) | Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 |
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| Secondary | Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib | Accumulation ratio for AUC was calculated as AUCtau for Day 22 divided by AUCtau for Day -7, where AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours. | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day -7 and Day 22 of Cycle 1 |
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| Secondary | Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib | Rss was calculated by dividing AUCtau at steady state (post multiple dosing on Day 22) by single dose AUCinf (on Day -7). AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours. AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). | The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here "overall number of participants analyzed" signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1; Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 |
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| Secondary | Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | OR in participants was defined as the percentage of participants with CR or PR as best response determined by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Number | Percentage of participants | From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 286 days) |
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| Secondary | Dose Escalation: Progression Free Survival (PFS) | PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. | FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Median | 95% Confidence Interval | Months | From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 286 days) |
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| Secondary | Dose Escalation: Duration of Response (DOR) | DOR was defined as the time between the date of the first documented objective response (PR or CR) and the date of the first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. | Due to no participants with response in dose escalation period, data collection and analysis for DOR was not performed. Hence, data is not reported. | Posted | From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 286 days) |
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| Secondary | Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | Confirmed OR in participants was defined as the percentage of participants with CR or PR as best response determined by BICR as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Number | 90% Confidence Interval | Percentage of participants | From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) |
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| Secondary | Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. | FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol. | Posted | Number | 90% Confidence Interval | Percentage of participants | Baseline up to Week 16, Baseline up to Week 24 |
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| Secondary | Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by BICR as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. | FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol. | Posted | Number | 90% Confidence Interval | Percentage of participants | Baseline up to Week 16, Baseline up to Week 24 |
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| Secondary | Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Analysis was performed on subset of participants with OR. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol. | Posted | Median | Full Range | Months | From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days) |
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| Secondary | Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by BICR according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Analysis was performed on subset of participants with OR. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol. | Posted | Median | Full Range | Months | From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days) |
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| Secondary | Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. | Analysis was performed on subset of participants with OR. | Posted | Median | 95% Confidence Interval | Months | From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) |
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| Secondary | Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. | Analysis was performed on subset of participants with OR. | Posted | Median | 95% Confidence Interval | Months | From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) |
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| Secondary | Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. | FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Median | 95% Confidence Interval | Months | From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days) |
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| Secondary | Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. | FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. | Posted | Median | 95% Confidence Interval | Months | From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days) |
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| Secondary | Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12 | OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at Month 12. Probability of participants who were event free at Month 12 was estimated by Kaplan-Meier method and reported. | FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol. | Posted | Number | 90% Confidence Interval | Probability of event free participants | At Month 12 |
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| Secondary | Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib | Pre dose plasma drug concentration. | The PK concentration analysis set included all enrolled participants who were treated and have at least 1 analyte concentration. Here "number analyzed" signifies number of participants evaluated for given time point. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram per milliliter | Pre dose at 0 hour on Day 1 of Cycle 2, 3, 4 and unplanned (any time during dose expansion period up to 502 days) |
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| 0 |
| 3 |
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Dose Escalation: Talazoparib 1.0 mg | Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | Dose Expansion: Talazoparib 1.0 mg | Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days). | 2 | 19 | 1 | 19 | 19 | 19 |
| Cholelithiasis | Hepatobiliary disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Cheilitis | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Dental caries | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Otitis media acute | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
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| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v23.1 | Non-systematic Assessment |
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| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Dyshidrotic eczema | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Essential hypertension | Vascular disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Epigastric discomfort | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Tooth loss | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Lymphocyte count decreased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Paralysis recurrent laryngeal nerve | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Nail pigmentation | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Malaise | General disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
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| Pericardial effusion | Cardiac disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Asthenopia | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Dry eye | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA v23.1 | Non-systematic Assessment |
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| Rib fracture | Injury, poisoning and procedural complications | MedDRA v23.1 | Non-systematic Assessment |
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| Tooth fracture | Injury, poisoning and procedural complications | MedDRA v23.1 | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
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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.
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| Alkaline phosphatase increased: Grade 1 |
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| Alkaline phosphatase increased: Grade 2 |
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| Aspartate aminotransferase increased: Grade 1 |
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| Blood bilirubin increased: Grade 1 |
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| Creatinine increased: Grade 1 |
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| Hyperglycemia: Grade 1 |
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| Hyperkalemia: Grade 1 |
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| Hypermagnesemia: Grade 1 |
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| Hypernatremia: Grade 1 |
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| Hypoalbuminemia: Grade 1 |
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| Hypoalbuminemia: Grade 2 |
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| Hypocalcemia: Grade 1 |
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| Hypoglycemia: Grade 1 |
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| Hypomagnesemia: Grade 1 |
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| Hyponatremia: Grade 1 |
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| Hypophosphatemia: Grade 2 |
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| Title | Measurements |
|---|---|
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| Anemia: Grade 3 |
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| Lymphocyte count decreased: Grade 1 |
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| Lymphocyte count decreased: Grade 2 |
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| Lymphocyte count decreased: Grade 3 |
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| Neutrophil count decreased: Grade 2 |
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| Neutrophil count decreased: Grade 3 |
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| Platelet count decreased: Grade 1 |
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| Platelet count decreased: Grade 2 |
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| White blood cell decreased: Grade 1 |
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| White blood cell decreased: Grade 2 |
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| White blood cell decreased: Grade 3 |
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| Cycle 4 Day 1 |
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| Unplanned |
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