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| ID | Type | Description | Link |
|---|---|---|---|
| C3441003 | Other Identifier | Alias Study Number | |
| 2016-001394-33 | EudraCT Number |
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| Name | Class |
|---|---|
| Medivation, Inc. | INDUSTRY |
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This study will evaluate the mass balance of talazoparib after a single dose of talazoparib.
Patients participating in this study with no clinically significant toxicities may be eligible to continue treatment on a separate extension protocol after discussion with the Principal Investigator and obtaining Sponsor permission..
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ADME | Experimental | 1 mg talazoparib containing100 μCi of 14C-radiolabeled talazoparib |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Talazoparib | Drug | 1 mg of talazoparib containing100 μCi of 14C-radiolabeled talazoparib |
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| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose | |
| Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose | |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Talazoparib | AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib | AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Terminal Elimination Half-Life (t1/2) of Talazoparib | Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Apparent Total Plasma Clearance (CL/F) of Talazoparib | Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes. |
| Measure | Description | Time Frame |
|---|---|---|
| Ratio of Maximum Observed Plasma Concentration to Maximum Observed Whole Blood Concentration for 14C- Radioactivity | 100 micro-curie of 14C radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRA Magyarorszag Kft, Fazis I-es Klinikai Farmakologiai Vizsgalohely | Budapest | 1077 | Hungary |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
| To obtain contact information for a study center near you, click here. | View source |
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This is a mass balance study with 14C-radiolabeled talazoparib in at least 6 participants with advanced solid tumors who qualified for treatment with talazoparib. Participants who completed the mass-balance part in this study had the option to continue treatment on an open-label extension protocol.
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| ID | Title | Description |
|---|---|---|
| FG000 | Talazoparib | Participants with advanced solid tumors received a single dose of talazoparib 1 miligram (mg) oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Safety analysis set included all participants who had received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Talazoparib | Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant). |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Pharmacokinetic (PK) population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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Day1 up to 14days after last day of mass balance phase and at least 30days after Day1/ before initiation of new cytotoxic chemotherapy, new investigational treatment/ first day of extension protocol, whichever occurs first (up to maximum duration of 8weeks from screening to follow-up for each participant)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who had received at least 1 dose of study drug.
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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 | Talazoparib | Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 19.1 | 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 | Oct 7, 2016 | May 25, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 16, 2017 | May 25, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C586365 | talazoparib |
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| Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Apparent Volume of Distribution (Vd/F) of Talazoparib | Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of the drug. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) of 14C- Radioactivity | 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Time to Attain Maximum Observed Plasma Concentration (Tmax) of 14C- Radioactivity | 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity | AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity | AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Terminal Elimination Half-Life (t1/2) of 14C- Radioactivity in Plasma | Terminal elimination half-life was defined as the time measured for the plasma radioactivity concentration to decrease by one half. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Apparent Total Plasma Clearance (CL/F) of 14C- Radioactivity | Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Plasma | Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Maximum Observed Whole Blood Concentration (Cmax) of 14C- Radioactivity | 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Time to Attain Maximum Observed Whole Blood Concentration (Tmax) of 14C- Radioactivity | 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity | AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity | AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Apparent Total Whole Blood Clearance (CL/F) of 14C- Radioactivity | Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Whole Blood | Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of the drug. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Amount of Talazoparib Excreted in Urine During Each Collection Interval (Ae t1-t2) | Ae t1-t2 was defined as the amount of talazoparib excreted into urine during each collection interval (t1-t2). | Pre-dose, 0 to 8 hours (hrs), 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose |
| Percentage of Dose of Talazoparib Excreted During Each Collection Interval (Aet1-t2%) of Talazoparib | Aet1-t2% was the percentage of Aet1-t2, where Aet1-t2 was defined as the amount of talazoparib excreted into urine during each collection interval (t1-t2). | Pre-dose, 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose |
| Renal Clearance (CLr) of Talazoparib | Renal clearance was calculated as cumulative amount of drug excreted in urine divided by AUC(0-last) (area under the plasma concentration-time curve from zero to the time of the last measurable concentration). | Pre-dose, 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose |
| The Recovery of 14C-Radioactivity as a Percentage of the Administered Dose | Recovery of 14C-radioactivity in urine and feces was calculated in terms of percentage of administered dose after administration of a single 1 mg dose of oral solution (containing 100 micro-curie 14C-labeled talazoparib). | From 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs and then after every 24 hrs until up to 504 hrs post-dose |
| Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity to Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity for 14C- Radioactivity |
AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. |
| Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration to Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable for 14C- Radioactivity | AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
| Number of Participants With Treatment Emergent Adverse Events (AEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug through 14 days after the last day of mass balance phase and at least 30 days after Day 1 or before initiation of new cytotoxic chemotherapy, new investigational treatment, or the first day of extension protocol, whichever occurs first (up to maximum duration of 8 weeks from screening to follow-up for each participant) or before initiation of new cytotoxic chemotherapy, new investigational treatment, or the first day of extension protocol, whichever occurs first, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both non-serious (AEs) and serious adverse events (SAEs). | Day 1 to 14 days after last day of mass balance phase and at least 30 days after Day1/before initiation of new cytotoxic chemotherapy, new investigational treatment/first day of extension protocol, whichever occurs first(up to maximum duration of 8 weeks) |
| Number of Participants With Clinically Significant Vital Signs Parameters | Vital Signs included heart rate, respiratory rate, body temperature, systolic blood pressure and diastolic blood pressure. clinical significance of vital signs was determined at the investigator's discretion. | Baseline up to Day 22 |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Criteria for clinically significant ECG abnormalities : Heart Rate; increase from baseline greater than (>)25 %and to a value >100, decrease from baseline >25% and to a value < 50; PR Interval: increase from baseline >25% and to a value >200; QRS Duration: increase from baseline >25% and to a value >100; QT interval using Fridericia's correction (QTcF): ranges >450 msec, >480 msec, >500 msec, Increase from baseline >30 msec and >60 msec; QT Interval: ranges >450 msec, >480 msec, >500 msec, Increase from baseline >30 msec and >60 msec. | Baseline up to Day 22 |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Haematological, biochemistry and urinalysis parameters. Biochemistry parameters:alkaline phosphatase 30-120units per liter(U/L), creatinine 53-110micromole/L(micromol/L), gamma glutamyl transferase 7-50U/L, glucose 3.3-5.5millimoles/L(mmol/L), lactate dehydrogenase 200-460U/L, triglycerides 0.4-1.7mmol/L, cholesterol 2.6-5.2mmol/L, phosphate 0.8-1.45mmol/L, sodium 135-146mmol/L, urea 2.8-7.2mmol/L, chloride 95-109mmol/L, creatine kinase 24-170U/L, aspartate aminotransferase 4-46U/L, potassium 3.5-5.5mmol/L. Haematology parameters:haemoglobin 120-155 gram/L(g/L), erythrocytes 4-5.2 10^12/L, haematocrit 0.35-0.45, prothrombin time 13.7-15.6 second(sec), lymphocytes 1-3.7 10^9/L, platelets 150-400 10^9/L, prothrombin intl. normalized ratio 0.89-1.1, activated partial thromboplastin time 25-43 sec, basophils 0-0.09 10^9/L, neutrophils 1.5-7 10^9/L, and leukocytes 4-10 10^9/L. Urinalysis parameters:urinalysis specific gravity 1.012-1.03, urinalysis pH 4.8-7.8. | Baseline up to Day 22 |
| Number of Participants With Change From Baseline in Physical Examination Findings | Physical examination included examination of abdomen, cardiovascular, eyes, ears, nose, throat, general appearance, head, neck, thyroid, lymph nodes, musculoskeletal, neurological, skin/subcutaneous tissue and thorax/lungs. | Baseline up to Day 22 |
| Amount of Any Significant Metabolites of Talazoparib in Urine and Feces | M4 (M481/1, cysteine conjugate of mono-desfluoro-talazoparib) metabolite was found in urine. MDV10595 (M1, dehydrogenated talazoparib (PF-07052386), M556/1 (glucuronide conjugate of talazoparib), and M2 (M396/1, mono-oxidative talazoparib) metabolites were calculated together and were also found in urine. Three metabolites named as: MDV10595 (M1)/M556/1 and M2 (M396/1) which were calculated together were detected in feces. Amount of metabolite in this outcome measure was measured in terms of percentage of dose of talazoparib. | From 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs and then after every 24 hrs until up to 504 hrs post-dose |
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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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| Units | Counts |
|---|---|
| Participants |
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| Primary | Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Median | Full Range | hours | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Talazoparib | AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | hour*nanogram per milliliter (hr*ng/mL) | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib | AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | hr*ng/mL | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Terminal Elimination Half-Life (t1/2) of Talazoparib | Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | hours | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Apparent Total Plasma Clearance (CL/F) of Talazoparib | Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | liter/hour | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Apparent Volume of Distribution (Vd/F) of Talazoparib | Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of the drug. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | liter | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Maximum Observed Plasma Concentration (Cmax) of 14C- Radioactivity | 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | nanogram equivalent/mililiter | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Time to Attain Maximum Observed Plasma Concentration (Tmax) of 14C- Radioactivity | 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Median | Full Range | hours | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity | AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | hour*nanogram equivalent/mililiter | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity | AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | hour*nanogram equivalent/mililiter | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Terminal Elimination Half-Life (t1/2) of 14C- Radioactivity in Plasma | Terminal elimination half-life was defined as the time measured for the plasma radioactivity concentration to decrease by one half. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | hours | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Apparent Total Plasma Clearance (CL/F) of 14C- Radioactivity | Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | liter/hour | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Plasma | Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | liter | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Maximum Observed Whole Blood Concentration (Cmax) of 14C- Radioactivity | 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | nanogram equivalent/mililiter | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Time to Attain Maximum Observed Whole Blood Concentration (Tmax) of 14C- Radioactivity | 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Median | Full Range | hours | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity | AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | hour*nanogram equivalent/mililiter | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity | AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | hour*nanogram equivalent/mililiter | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Apparent Total Whole Blood Clearance (CL/F) of 14C- Radioactivity | Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | liter/hour | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Whole Blood | Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of the drug. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | liter | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Primary | Amount of Talazoparib Excreted in Urine During Each Collection Interval (Ae t1-t2) | Ae t1-t2 was defined as the amount of talazoparib excreted into urine during each collection interval (t1-t2). | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | micrograms | Pre-dose, 0 to 8 hours (hrs), 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose |
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| Primary | Percentage of Dose of Talazoparib Excreted During Each Collection Interval (Aet1-t2%) of Talazoparib | Aet1-t2% was the percentage of Aet1-t2, where Aet1-t2 was defined as the amount of talazoparib excreted into urine during each collection interval (t1-t2). | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | percentage of dose | Pre-dose, 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose |
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| Primary | Renal Clearance (CLr) of Talazoparib | Renal clearance was calculated as cumulative amount of drug excreted in urine divided by AUC(0-last) (area under the plasma concentration-time curve from zero to the time of the last measurable concentration). | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | liter/hour | Pre-dose, 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose |
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| Primary | The Recovery of 14C-Radioactivity as a Percentage of the Administered Dose | Recovery of 14C-radioactivity in urine and feces was calculated in terms of percentage of administered dose after administration of a single 1 mg dose of oral solution (containing 100 micro-curie 14C-labeled talazoparib). | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | Percentage of dose | From 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs and then after every 24 hrs until up to 504 hrs post-dose |
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| Secondary | Ratio of Maximum Observed Plasma Concentration to Maximum Observed Whole Blood Concentration for 14C- Radioactivity | 100 micro-curie of 14C radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | ratio | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Secondary | Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity to Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity for 14C- Radioactivity | AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | ratio | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Secondary | Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration to Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable for 14C- Radioactivity | AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Mean | Standard Deviation | ratio | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (AEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug through 14 days after the last day of mass balance phase and at least 30 days after Day 1 or before initiation of new cytotoxic chemotherapy, new investigational treatment, or the first day of extension protocol, whichever occurs first (up to maximum duration of 8 weeks from screening to follow-up for each participant) or before initiation of new cytotoxic chemotherapy, new investigational treatment, or the first day of extension protocol, whichever occurs first, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both non-serious (AEs) and serious adverse events (SAEs). | Safety analysis set included all participants who received at least 1 dose of talazoparib. | Posted | Number | participants | Day 1 to 14 days after last day of mass balance phase and at least 30 days after Day1/before initiation of new cytotoxic chemotherapy, new investigational treatment/first day of extension protocol, whichever occurs first(up to maximum duration of 8 weeks) |
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| Secondary | Number of Participants With Clinically Significant Vital Signs Parameters | Vital Signs included heart rate, respiratory rate, body temperature, systolic blood pressure and diastolic blood pressure. clinical significance of vital signs was determined at the investigator's discretion. | Safety analysis set included all participants who received at least 1 dose of talazoparib. | Posted | Number | participants | Baseline up to Day 22 |
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| Secondary | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Criteria for clinically significant ECG abnormalities : Heart Rate; increase from baseline greater than (>)25 %and to a value >100, decrease from baseline >25% and to a value < 50; PR Interval: increase from baseline >25% and to a value >200; QRS Duration: increase from baseline >25% and to a value >100; QT interval using Fridericia's correction (QTcF): ranges >450 msec, >480 msec, >500 msec, Increase from baseline >30 msec and >60 msec; QT Interval: ranges >450 msec, >480 msec, >500 msec, Increase from baseline >30 msec and >60 msec. | Safety population set included all participants who received at least 1 dose of talazoparib. | Posted | Number | participants | Baseline up to Day 22 |
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| Secondary | Number of Participants With Clinically Significant Laboratory Abnormalities | Haematological, biochemistry and urinalysis parameters. Biochemistry parameters:alkaline phosphatase 30-120units per liter(U/L), creatinine 53-110micromole/L(micromol/L), gamma glutamyl transferase 7-50U/L, glucose 3.3-5.5millimoles/L(mmol/L), lactate dehydrogenase 200-460U/L, triglycerides 0.4-1.7mmol/L, cholesterol 2.6-5.2mmol/L, phosphate 0.8-1.45mmol/L, sodium 135-146mmol/L, urea 2.8-7.2mmol/L, chloride 95-109mmol/L, creatine kinase 24-170U/L, aspartate aminotransferase 4-46U/L, potassium 3.5-5.5mmol/L. Haematology parameters:haemoglobin 120-155 gram/L(g/L), erythrocytes 4-5.2 10^12/L, haematocrit 0.35-0.45, prothrombin time 13.7-15.6 second(sec), lymphocytes 1-3.7 10^9/L, platelets 150-400 10^9/L, prothrombin intl. normalized ratio 0.89-1.1, activated partial thromboplastin time 25-43 sec, basophils 0-0.09 10^9/L, neutrophils 1.5-7 10^9/L, and leukocytes 4-10 10^9/L. Urinalysis parameters:urinalysis specific gravity 1.012-1.03, urinalysis pH 4.8-7.8. | Safety population set included all participants who received at least 1 dose of talazoparib. | Posted | Number | participants | Baseline up to Day 22 |
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| Secondary | Number of Participants With Change From Baseline in Physical Examination Findings | Physical examination included examination of abdomen, cardiovascular, eyes, ears, nose, throat, general appearance, head, neck, thyroid, lymph nodes, musculoskeletal, neurological, skin/subcutaneous tissue and thorax/lungs. | Safety population set included all participants who received at least 1 dose of talazoparib. | Posted | Number | participants | Baseline up to Day 22 |
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| Secondary | Amount of Any Significant Metabolites of Talazoparib in Urine and Feces | M4 (M481/1, cysteine conjugate of mono-desfluoro-talazoparib) metabolite was found in urine. MDV10595 (M1, dehydrogenated talazoparib (PF-07052386), M556/1 (glucuronide conjugate of talazoparib), and M2 (M396/1, mono-oxidative talazoparib) metabolites were calculated together and were also found in urine. Three metabolites named as: MDV10595 (M1)/M556/1 and M2 (M396/1) which were calculated together were detected in feces. Amount of metabolite in this outcome measure was measured in terms of percentage of dose of talazoparib. | PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data. | Posted | Number | percentage of dose | From 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs and then after every 24 hrs until up to 504 hrs post-dose |
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| 0 |
| 6 |
| 0 |
| 6 |
| 4 |
| 6 |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Non-systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 19.1 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 19.1 | Non-systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA 19.1 | 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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