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| ID | Type | Description | Link |
|---|---|---|---|
| C3441001 | Other Identifier | Alias Study Number | |
| 2016-002536-33 | EudraCT Number |
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| Name | Class |
|---|---|
| Medivation, Inc. | INDUSTRY |
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This trial will investigate the pharmacokinetics (PK) and safety of talazoparib in patients with advanced solid tumors and impaired renal function.
At the End of the Study, patients with no clinically significant toxicities, no contraindications to continue treatment with talazoparib, and no disease progression (underlying cancer progression) may be eligible to continue talazoparib treatment in a separate open-label extension study after discussion with the Principal Investigator and obtaining Sponsor permission. Sponsor decision to allow the patient to continue dosing with talazoparib in an open-label extension study will be based on potential overall benefit-risk, patient acceptance and other relevant criteria.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A (control, normal renal function) | Experimental |
| |
| Group B (mild renal impairment) | Experimental |
| |
| Group C (moderate renal impairment) | Experimental |
| |
| Group D (severe renal impairment) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Talazoparib | Drug | Daily oral doses of talazoparib 0.5 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
| Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cmax was defined as the maximum observed plasma concentration of talazoparib. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
| Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib | AUC0-24u for unbound talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
| Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
| Measure | Description | Time Frame |
|---|---|---|
| Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
| Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib |
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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 |
|---|---|---|---|---|---|---|
| Fort Wayne Medical Oncology and Hematology, Inc. | Fort Wayne | Indiana | 46804 | United States | ||
| Fort Wayne Medical Oncology and Hematology, Inc. |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33686631 | Derived | Durairaj C, Chakrabarti J, Ferrario C, Hirte HW, Babu S, Piha-Paul SA, Plotka A, Hoffman J, Shi H, Wang DD. The Effect of Renal Impairment on the Pharmacokinetics and Safety of Talazoparib in Patients with Advanced Solid Tumors. Clin Pharmacokinet. 2021 Jul;60(7):921-930. doi: 10.1007/s40262-020-00983-y. Epub 2021 Mar 9. |
| 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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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Renal Function | Participants with normal renal function (estimated glomerular filtration rate [eGFR] greater than or equal to [>=] 90 milliliter per minute per 1.73 square meter [mL/min/1.73m^2]) received 0.5 milligrams (mg) (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
| FG001 | Mild Renal Impairment | Participants with mild renal function (eGFR >= 60 and less than or equal to [<=] 89 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
| FG002 | Moderate Renal Impairment | Participants with moderate renal function (eGFR >= 30 and <=59 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
| FG003 | Severe Renal Impairment | Participants with severe renal function (eGFR >= 15 and <= 29 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety analysis included all participants who received any amount of talazoparib.
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Renal Function | Participants with normal renal function (eGFR >= 90 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
| BG001 | Mild Renal Impairment |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose. | Pharmacokinetic (PK) analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
|
Baseline up to 30 days after last dose of study drug (up to 52 days)
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.
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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 | Normal Renal Function | Participants with normal renal function (eGFR >= 90 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CONDITION AGGRAVATED | General disorders | MedDRA v21.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA v21.1 | 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 | Aug 31, 2018 | Jan 6, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 28, 2019 | Jan 6, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C586365 | talazoparib |
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|
Cmax was defined as the maximum observed plasma concentration of talazoparib. |
| Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
| Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
| Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
| Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib | AUC0-24u for unbound talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours for unbound talazoparib. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
| Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
| Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
| Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib | Ctrough was defined as plasma trough (predose) concentration of talazoparib. | Predose on Day 22 |
| Multiple Dose: Apparent Oral Clearance (CL/F) of Talazoparib | Drug clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
| Multiple Dose: Accumulation Ratio (Rac) of AUC (0-24) | Accumulation ratio for AUC0-24 was calculated as area under the curve from time zero to 24 hours on Day 22 divided by area under the curve from time zero to 24 hours on Day 1. | Pre-dose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 and Day 22 |
| Multiple Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration. | Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22 |
| Multiple Dose: Unbound Apparent Oral Clearance (CLu/F) of Talazoparib | Clearance of unbound drug is a measure of the rate at which unbound drug is metabolized or eliminated by normal biological processes. | Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22 |
| Single Dose: Amount of Talazoparib Excreted Unchanged in Urine From Time 0 to 24 Hours (Ae 0-24) | Ae 0-24 is the amount of drug excreted unchanged in urine from time 0 to 24 hours postdose. | 0 to 24 hours on Day 1 |
| Single Dose: Percentage of Dose of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) at Day 1 | Ae0-24% was defined as the amount of drug excreted in urine from time 0 to 24 hours expressed as percentage of administered dose. | 0 to 24 hours on Day 1 |
| Multiple Dose: Amount of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) | Ae 0-24 is the amount of drug excreted unchanged in urine from time 0 to 24 hours postdose. | 0 to 24 hours on Day 22 |
| Multiple Dose: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24 %) of Talazoparib at Day 22 | Ae 0-24% was defined as the amount of drug excreted in urine from time 0 to 24 hours, expressed as percentage of administered dose. | 0 to 24 hours on Day 22 |
| Multiple Dose: Renal Clearance (CLr) of Talazoparib at Day 22 | Renal clearance was calculated as cumulative amount of drug excreted in urine during the 24 hours dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to 24 hours postdose. | 0 to 24 hours on Day 22 |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of investigational product and up to 30 days after the last dose of investigational product (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. | Baseline up to 30 days after last dose of study drug (up to 52 days) |
| Number of Participants With Abnormalities in Physical Examination | Physical examination included examination of the general appearance, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Findings were considered to be abnormal based on investigator's decision. | Baseline up to 30 days after last dose of study drug (up to 52 days) |
| Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) |
| Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) |
| Change From Baseline in Heart Rate of Participants | Heart rate was measured in terms of beats per minute. | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) |
| Change From Baseline in Respiratory Rate of Participants | Respiratory rate was measured in terms of breaths per minute. | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) |
| Change From Baseline in Body Weight of Participants | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) |
| Number of Participants With Electrocardiogram (ECG) Abnormalities | ECG parameters included pulse rate (PR) interval, QRS duration, QT interval and corrected QT interval using Fridericia's formula (QTcF). Abnormality criteria: 1) PR interval: greater than equal to (>=) 25 percent (%) increase when baseline >= 300 msec; 2) QRS duration: >=50% increase when baseline >=140 msec; 3) QT interval: >= 500 msec: 4) QTCF interval: QTc interval using Fridericia's formula (QTcF interval) >= 500 msec when baseline >= 60. IFB stands for increase from baseline. | Baseline up to 30 days after last dose of study drug (up to 52 days) |
| Number of Participants With Laboratory Abnormalities | Laboratory parameters: erythrocytes, hematocrit, hemoglobin, white blood cells, absolute neutrophil count, lymphocytes, platelets ; albumin, alkaline phosphatase, alanine aminotransferase, aspartate transaminase , bilirubin, bicarbonate, blood urea nitrogen , calcium, chloride, creatinine, gamma -glutamyl transferase, glucose, lactate dehydrogenase, sodium, phosphate, potassium, total protein, uric acid, follicle-stimulating hormone; international normalized ratio / prothrombin time [activated] partial thromboplastin time; Urinalysis (pH, specific gravity, protein, glucose, ketones, bilirubin, blood, leukocyte esterase); Serum pregnancy test; Serology for Human Immunodeficiency Virus (HIV). Number of participants with laboratory test abnormalities as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) version 4.03 were reported: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. | Baseline up to 30 days after last dose of study drug (up to 52 days) |
| Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | As per ECOG, participant's performance status was measured on 5 point scale: 0=fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature, e.g., light housework, office work. 2= ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5: dead. | Baseline, Safety follow up (Day 52) |
| Fort Wayne |
| Indiana |
| 46845 |
| United States |
| Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Karmanos Cancer Institute Weisberg Cancer Treatment Center | Farmington Hills | Michigan | 48334 | United States |
| Robert Wood Johnson University Hospital | New Brunswick | New Jersey | 08901 | United States |
| Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | 08903 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Cross Cancer Institute | Edmonton | Alberta | T6G 1Z2 | Canada |
| Juravinski Cancer Centre | Hamilton | Ontario | L8V 5C2 | Canada |
| Jewish General Hospital | Montreal | Quebec | H3T 1E2 | Canada |
Participants with mild renal function (eGFR >= 60 and >=89 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
| BG002 | Moderate Renal Impairment | Participants with moderate renal function (eGFR >= 30 and <=59 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
| BG003 | Severe Renal Impairment | Participants with severe renal function (eGFR >= 15 and <= 29 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Participants with mild renal function (eGFR >= 60 and >=89 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
| OG002 | Moderate Renal Impairment | Participants with moderate renal function (eGFR >= 30 and <=59 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
| OG003 | Severe Renal Impairment | Participants with severe renal function (eGFR >= 15 and <= 29 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. |
|
|
|
| Primary | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cmax was defined as the maximum observed plasma concentration of talazoparib. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
|
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|
|
| Primary | Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib | AUC0-24u for unbound talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
|
|
|
|
| Primary | Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
|
|
|
|
| Secondary | Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
|
|
|
| Secondary | Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cmax was defined as the maximum observed plasma concentration of talazoparib. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
|
|
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| Secondary | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Median | Full Range | hours | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
|
|
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| Secondary | Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
|
|
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| Secondary | Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib | AUC0-24u for unbound talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours for unbound talazoparib. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
|
|
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| Secondary | Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 |
|
|
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| Secondary | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Median | Full Range | hours | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
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| Secondary | Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib | Ctrough was defined as plasma trough (predose) concentration of talazoparib. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter | Predose on Day 22 |
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| Secondary | Multiple Dose: Apparent Oral Clearance (CL/F) of Talazoparib | Drug clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters per hour | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 |
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| Secondary | Multiple Dose: Accumulation Ratio (Rac) of AUC (0-24) | Accumulation ratio for AUC0-24 was calculated as area under the curve from time zero to 24 hours on Day 22 divided by area under the curve from time zero to 24 hours on Day 1. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Pre-dose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 and Day 22 |
|
|
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| Secondary | Multiple Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22 |
|
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| Secondary | Multiple Dose: Unbound Apparent Oral Clearance (CLu/F) of Talazoparib | Clearance of unbound drug is a measure of the rate at which unbound drug is metabolized or eliminated by normal biological processes. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters per hour | Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22 |
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| Secondary | Single Dose: Amount of Talazoparib Excreted Unchanged in Urine From Time 0 to 24 Hours (Ae 0-24) | Ae 0-24 is the amount of drug excreted unchanged in urine from time 0 to 24 hours postdose. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | milligram | 0 to 24 hours on Day 1 |
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| Secondary | Single Dose: Percentage of Dose of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) at Day 1 | Ae0-24% was defined as the amount of drug excreted in urine from time 0 to 24 hours expressed as percentage of administered dose. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose | 0 to 24 hours on Day 1 |
|
|
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| Secondary | Multiple Dose: Amount of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) | Ae 0-24 is the amount of drug excreted unchanged in urine from time 0 to 24 hours postdose. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | milligram | 0 to 24 hours on Day 22 |
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| Secondary | Multiple Dose: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24 %) of Talazoparib at Day 22 | Ae 0-24% was defined as the amount of drug excreted in urine from time 0 to 24 hours, expressed as percentage of administered dose. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose | 0 to 24 hours on Day 22 |
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| Secondary | Multiple Dose: Renal Clearance (CLr) of Talazoparib at Day 22 | Renal clearance was calculated as cumulative amount of drug excreted in urine during the 24 hours dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to 24 hours postdose. | PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters per hour | 0 to 24 hours on Day 22 |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of investigational product and up to 30 days after the last dose of investigational product (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. | Safety analysis included all participants who received any amount of talazoparib. | Posted | Count of Participants | Participants | Baseline up to 30 days after last dose of study drug (up to 52 days) |
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| Secondary | Number of Participants With Abnormalities in Physical Examination | Physical examination included examination of the general appearance, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Findings were considered to be abnormal based on investigator's decision. | Safety analysis included all participants who received any amount of talazoparib. | Posted | Count of Participants | Participants | Baseline up to 30 days after last dose of study drug (up to 52 days) |
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| Secondary | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Safety analysis included all participants who received any amount of talazoparib. Here, "number analyzed" signifies participants evaluable for specific rows. | Posted | Mean | Standard Deviation | millimeters of mercury (mmHg) | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) |
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| Secondary | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Safety analysis included all participants who received any amount of talazoparib. Here, "number analyzed" signifies participants evaluable for specific rows. | Posted | Mean | Standard Deviation | mmHg | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) |
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| Secondary | Change From Baseline in Heart Rate of Participants | Heart rate was measured in terms of beats per minute. | Safety analysis included all participants who received any amount of talazoparib. Here, "number analyzed" signifies participants evaluable for specific rows. | Posted | Mean | Standard Deviation | beats per minute | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) |
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| Secondary | Change From Baseline in Respiratory Rate of Participants | Respiratory rate was measured in terms of breaths per minute. | Safety analysis included all participants who received any amount of talazoparib. Here, "number analyzed" signifies participants evaluable for specific rows. | Posted | Mean | Standard Deviation | breaths per minute | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) |
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| Secondary | Change From Baseline in Body Weight of Participants | Safety analysis included all participants who received any amount of talazoparib. Here, "number analyzed" signifies participants evaluable for specific rows. | Posted | Mean | Standard Deviation | kilograms | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) |
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| Secondary | Number of Participants With Electrocardiogram (ECG) Abnormalities | ECG parameters included pulse rate (PR) interval, QRS duration, QT interval and corrected QT interval using Fridericia's formula (QTcF). Abnormality criteria: 1) PR interval: greater than equal to (>=) 25 percent (%) increase when baseline >= 300 msec; 2) QRS duration: >=50% increase when baseline >=140 msec; 3) QT interval: >= 500 msec: 4) QTCF interval: QTc interval using Fridericia's formula (QTcF interval) >= 500 msec when baseline >= 60. IFB stands for increase from baseline. | Safety analysis included all participants who received any amount of talazoparib. | Posted | Count of Participants | Participants | Baseline up to 30 days after last dose of study drug (up to 52 days) |
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| Secondary | Number of Participants With Laboratory Abnormalities | Laboratory parameters: erythrocytes, hematocrit, hemoglobin, white blood cells, absolute neutrophil count, lymphocytes, platelets ; albumin, alkaline phosphatase, alanine aminotransferase, aspartate transaminase , bilirubin, bicarbonate, blood urea nitrogen , calcium, chloride, creatinine, gamma -glutamyl transferase, glucose, lactate dehydrogenase, sodium, phosphate, potassium, total protein, uric acid, follicle-stimulating hormone; international normalized ratio / prothrombin time [activated] partial thromboplastin time; Urinalysis (pH, specific gravity, protein, glucose, ketones, bilirubin, blood, leukocyte esterase); Serum pregnancy test; Serology for Human Immunodeficiency Virus (HIV). Number of participants with laboratory test abnormalities as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) version 4.03 were reported: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. | Safety analysis included all participants who received any amount of talazoparib. | Posted | Count of Participants | Participants | Baseline up to 30 days after last dose of study drug (up to 52 days) |
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| Secondary | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | As per ECOG, participant's performance status was measured on 5 point scale: 0=fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature, e.g., light housework, office work. 2= ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5: dead. | Safety analysis included all participants who received any amount of talazoparib. Here, "Number Analyzed" signifies participants who were evaluable at specific rows. | Posted | Count of Participants | Participants | Baseline, Safety follow up (Day 52) |
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| 1 |
| 9 |
| 1 |
| 9 |
| 7 |
| 9 |
| EG001 | Mild Renal Impairment | Participants with mild renal function (eGFR >= 60 and >=89 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. | 0 | 9 | 0 | 9 | 8 | 9 |
| EG002 | Moderate Renal Impairment | Participants with moderate renal function (eGFR >= 30 and <=59 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. | 0 | 8 | 0 | 8 | 8 | 8 |
| EG003 | Severe Renal Impairment | Participants with severe renal function (eGFR >= 15 and <= 29 mL/min/1.73m^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. | 1 | 8 | 2 | 8 | 7 | 8 |
| PNEUMONIA | Infections and infestations | MedDRA v21.1 | Non-systematic Assessment |
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| DEHYDRATION | Metabolism and nutrition disorders | MedDRA v21.1 | Non-systematic Assessment |
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| METABOLIC ACIDOSIS | Metabolism and nutrition disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| LEUKOCYTOSIS | Blood and lymphatic system disorders | MedDRA v21.1 | Non-systematic Assessment |
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| THROMBOCYTOPENIA | Blood and lymphatic system disorders | MedDRA v21.1 | Non-systematic Assessment |
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| PALPITATIONS | Cardiac disorders | MedDRA v21.1 | Non-systematic Assessment |
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| TACHYCARDIA | Cardiac disorders | MedDRA v21.1 | Non-systematic Assessment |
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| VISION BLURRED | Eye disorders | MedDRA v21.1 | Non-systematic Assessment |
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| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| CONSTIPATION | Gastrointestinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DIARRHOEA | Gastrointestinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DRY MOUTH | Gastrointestinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DYSPEPSIA | Gastrointestinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| VOMITING | Gastrointestinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| CHILLS | General disorders | MedDRA v21.1 | Non-systematic Assessment |
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| FATIGUE | General disorders | MedDRA v21.1 | Non-systematic Assessment |
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| GAIT DISTURBANCE | General disorders | MedDRA v21.1 | Non-systematic Assessment |
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| INJECTION SITE BRUISING | General disorders | MedDRA v21.1 | Non-systematic Assessment |
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| OEDEMA PERIPHERAL | General disorders | MedDRA v21.1 | Non-systematic Assessment |
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| PERIPHERAL SWELLING | General disorders | MedDRA v21.1 | Non-systematic Assessment |
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| PYREXIA | General disorders | MedDRA v21.1 | Non-systematic Assessment |
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| URINARY TRACT INFECTION | Infections and infestations | MedDRA v21.1 | Non-systematic Assessment |
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| SUNBURN | Injury, poisoning and procedural complications | MedDRA v21.1 | Non-systematic Assessment |
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| VASCULAR ACCESS COMPLICATION | Injury, poisoning and procedural complications | MedDRA v21.1 | Non-systematic Assessment |
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| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA v21.1 | Non-systematic Assessment |
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| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA v21.1 | Non-systematic Assessment |
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| BLOOD ALBUMIN DECREASED | Investigations | MedDRA v21.1 | Non-systematic Assessment |
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| BLOOD BILIRUBIN INCREASED | Investigations | MedDRA v21.1 | Non-systematic Assessment |
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| HYPERTENSION | Vascular disorders | MedDRA v21.1 | Non-systematic Assessment |
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| BLOOD POTASSIUM INCREASED | Investigations | MedDRA v21.1 | Non-systematic Assessment |
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| EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE STATUS WORSENED | Investigations | MedDRA v21.1 | Non-systematic Assessment |
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| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DEHYDRATION | Metabolism and nutrition disorders | MedDRA v21.1 | Non-systematic Assessment |
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| HYPOCALCAEMIA | Metabolism and nutrition disorders | MedDRA v21.1 | Non-systematic Assessment |
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| HYPOKALAEMIA | Metabolism and nutrition disorders | MedDRA v21.1 | Non-systematic Assessment |
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| HYPOMAGNESAEMIA | Metabolism and nutrition disorders | MedDRA v21.1 | Non-systematic Assessment |
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| HYPONATRAEMIA | Metabolism and nutrition disorders | MedDRA v21.1 | Non-systematic Assessment |
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| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| FLANK PAIN | Musculoskeletal and connective tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| JOINT SWELLING | Musculoskeletal and connective tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| MUSCULOSKELETAL CHEST PAIN | Musculoskeletal and connective tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| MUSCULOSKELETAL PAIN | Musculoskeletal and connective tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| OSTEOARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DYSGEUSIA | Nervous system disorders | MedDRA v21.1 | Non-systematic Assessment |
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| HYPOAESTHESIA | Nervous system disorders | MedDRA v21.1 | Non-systematic Assessment |
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| PARAESTHESIA | Nervous system disorders | MedDRA v21.1 | Non-systematic Assessment |
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| SOMNOLENCE | Nervous system disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DEPRESSION | Psychiatric disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DYSURIA | Renal and urinary disorders | MedDRA v21.1 | Non-systematic Assessment |
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| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| PRODUCTIVE COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| WHEEZING | Respiratory, thoracic and mediastinal disorders | MedDRA v21.1 | Non-systematic Assessment |
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| COLD SWEAT | Skin and subcutaneous tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| DERMATITIS ACNEIFORM | Skin and subcutaneous tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| ERYTHEMA | Skin and subcutaneous tissue disorders | MedDRA v21.1 | Non-systematic Assessment |
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| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA v21.1 | 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.
| Percent Ratio of Geometric Means |
| 131.57 |
| 2-Sided |
| 90 |
| 89.12 |
| 194.25 |
| Superiority |
| Percent Ratio of Geometric Means | 189.32 | 2-Sided | 90 | 126.74 | 282.80 | Superiority |
| Percent Ratio of Geometric Means |
| 139.34 |
| 2-Sided |
| 90 |
| 99.53 |
| 195.06 |
| Superiority |
| Percent Ratio of Geometric Means | 286.61 | 2-Sided | 90 | 202.66 | 405.33 | Superiority |
| Percent Ratio of Geometric Means |
| 128.22 |
| 2-Sided |
| 90 |
| 88.05 |
| 186.72 |
| Superiority |
| Percent Ratio of Geometric Means | 206.07 | 2-Sided | 90 | 139.91 | 303.51 | Superiority |
| SAEs |
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| Change at Day 8 |
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| Change at Day 15 |
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| Change at Day 22 |
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| Change at Day 52 |
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| Change at Day 8 |
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| Change at Day 15 |
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| Change at Day 22 |
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| Change at Day 52 |
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| Change at Day 8 |
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| Change at Day 15 |
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| Change at Day 22 |
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| Change at Day 52 |
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| Change at Day 8 |
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| Change at Day 15 |
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| Change at Day 22 |
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| Change at Day 52 |
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| Change at Day 8 |
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| Change at Day 15 |
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| Change at Day 22 |
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| Change at Day 52 |
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| Grade 2 |
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| Grade 3 |
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| Grade 4 |
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| Day 52 |
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| ECOG: 1 |
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| ECOG: 2 |
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| ECOG: 3 |
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| ECOG: 4 |
|