Advanced Solid Tumors
Conditions
Brief summary
This trial will investigate the pharmacokinetics (PK) and safety of talazoparib in patients with advanced solid tumors and impaired renal function.
Detailed description
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.
Interventions
DRUGTalazoparib
Daily oral doses of talazoparib 0.5 mg
Sponsors
Medivation, Inc.
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed and dated informed consent form (by the patient or a legally acceptable representative as per the local regulations) obtained prior to initiation of any study-specific procedure and treatment. 2. Female or male of at least 18 years of age. 3. Histologically or cytologically confirmed advanced solid tumor with no available standard approved treatment options in the opinion of the Investigator 4. Eastern Cooperative Oncology Group (ECOG) Performance status (PS) ≤ 2. 5. Expected life expectancy of ≥ 3 months. 6. Able to swallow the study drug (no contra indication to oral agents). 7. Renal function at screening and enrollment as defined by the Modification of Diet in Renal Disease (MDRD) equation. 8. Patient has had no clinically significant change in renal status within 3 months prior to screening, according to Investigator's review of clinical patient records. 9. Patient is not currently on hemodialysis and/or peritoneal dialysis for management of chronic kidney disease or acute failure/conditions. 10. Patient has no unstable renal function, defined as a change in estimated glomerular filtration rate (eGFR) (calculated with the MDRD equation) of \> 25% for patients with mild and moderate renal impaired or as a change in eGFR \> 30% for patients with severe renal impaired, from screening to enrollment. 11. Adequate other organ function at screening and enrollment. 12. Female patients of childbearing potential must have a negative serum pregnancy test at screening, and must agree to use a highly effective birth control method from the time of the first dose of study drug through 45 days after the last dose of study drug. 13. Male patients must agree to use a condom when having sex with a pregnant woman or with a non-pregnant female partner of childbearing potential, from 21 days before the first dose of study drug through 105 days after last dose of study drug. 14. Female patients must not be breastfeeding at screening nor during the study participation until 45 days after the last dose of study drug. 15. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Exclusion criteria
1. Treatment within 14 days or five half lives prior to enrollment with any type of systemic anticancer-therapy or any investigational drug, whichever is longer. 2. Have not recovered (recovery is defined as CTCAE grade ≤ 1) from the acute toxicities of previous anticancer standard or investigational therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements. 3. Major surgery within 28 days prior to enrollment. 4. Serious accompanying cardiac disorder. 5. Active known or suspected brain metastasis or active leptomeningeal disease undergoing or requiring treatment. 6. Symptomatic or impending spinal cord compression or cauda equina syndrome. 7. Has undergone a liver transplant, kidney transplant or nephrectomy. 8. Prior allergic reaction or severe intolerance (meeting the criteria for a serious adverse event, a grade 3 or 4 AE, or permanent treatment discontinuation) to a poly ADP ribose polymerase (PARP) inhibitor. 9. Known myelodysplastic syndrome. 10. Seropositive for human immunodeficiency virus (HIV). 11. Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol. 12. Gastrointestinal disorder affecting absorption. 13. Known or suspected hypersensitivity to any of the talazoparib capsule components. 14. Any condition or reason that interferes with ability to participate in the study, tolerate treatment or assessments associated with the protocol, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator or Medical Monitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 | AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose. |
| Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 | Cmax was defined as the maximum observed plasma concentration of talazoparib. |
| Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 | AUC0-24u for unbound talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose. |
| Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 | Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 | AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose. |
| Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 | Cmax was defined as the maximum observed plasma concentration of talazoparib. |
| Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. |
| Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 | Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration. |
| Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 | AUC0-24u for unbound talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours for unbound talazoparib. |
| Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 | Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. |
| Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. |
| Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib | Predose on Day 22 | Ctrough was defined as plasma trough (predose) concentration of talazoparib. |
| Multiple Dose: Apparent Oral Clearance (CL/F) of Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22 | Drug clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. |
| Multiple Dose: Accumulation Ratio (Rac) of AUC (0-24) | Pre-dose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 and Day 22 | 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. |
| Multiple Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22 | Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration. |
| Multiple Dose: Unbound Apparent Oral Clearance (CLu/F) of Talazoparib | Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22 | Clearance of unbound drug is a measure of the rate at which unbound drug is metabolized or eliminated by normal biological processes. |
| Single Dose: Amount of Talazoparib Excreted Unchanged in Urine From Time 0 to 24 Hours (Ae 0-24) | 0 to 24 hours on Day 1 | Ae 0-24 is the amount of drug excreted unchanged in urine from time 0 to 24 hours postdose. |
| Single Dose: Percentage of Dose of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) at Day 1 | 0 to 24 hours on 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. |
| Multiple Dose: Amount of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) | 0 to 24 hours on Day 22 | Ae 0-24 is the amount of drug excreted unchanged in urine from time 0 to 24 hours postdose. |
| Multiple Dose: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24 %) of Talazoparib at Day 22 | 0 to 24 hours on 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. |
| Multiple Dose: Renal Clearance (CLr) of Talazoparib at Day 22 | 0 to 24 hours on 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline up to 30 days after last dose of study drug (up to 52 days) | 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. |
| Number of Participants With Abnormalities in Physical Examination | Baseline up to 30 days after last dose of study drug (up to 52 days) | 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. |
| 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 | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) | Heart rate was measured in terms of beats per minute. |
| Change From Baseline in Respiratory Rate of Participants | Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52) | Respiratory rate was measured in terms of breaths per minute. |
| 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 | Baseline up to 30 days after last dose of study drug (up to 52 days) | 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. |
| Number of Participants With Laboratory Abnormalities | Baseline up to 30 days after last dose of study drug (up to 52 days) | 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. |
| Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline, Safety follow up (Day 52) | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| 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. | 9 |
| 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. | 8 |
| 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. | 8 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|---|---|
| Age, Continuous | 65.4 years STANDARD_DEVIATION 10.2 | 59.1 years STANDARD_DEVIATION 6.99 | 65.4 years STANDARD_DEVIATION 9.13 | 65.3 years STANDARD_DEVIATION 6.45 | 72.8 years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 9 Participants | 9 Participants | 7 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 7 Participants | 8 Participants | 7 Participants | 7 Participants |
| Sex: Female, Male Female | 22 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants |
| Sex: Female, Male Male | 12 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 9 | 0 / 9 | 0 / 8 | 1 / 8 |
| other Total, other adverse events | 7 / 9 | 8 / 9 | 8 / 8 | 7 / 8 |
| serious Total, serious adverse events | 1 / 9 | 0 / 9 | 0 / 8 | 2 / 8 |
Outcome results
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.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
Population: Pharmacokinetic (PK) analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | 94.88 nanogram*hour per milliliter | Geometric Coefficient of Variation 27 |
| Mild Renal Impairment | Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | 106.5 nanogram*hour per milliliter | Geometric Coefficient of Variation 40 |
| Moderate Renal Impairment | Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | 135.7 nanogram*hour per milliliter | Geometric Coefficient of Variation 45 |
| Severe Renal Impairment | Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | 249.8 nanogram*hour per milliliter | Geometric Coefficient of Variation 30 |
90% CI: [80.06, 157.26]
90% CI: [103.03, 198.42]
90% CI: [187.88, 369.06]
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.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib | 28.33 nanogram*hour per milliliter | Geometric Coefficient of Variation 32 |
| Mild Renal Impairment | Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib | 33.59 nanogram*hour per milliliter | Geometric Coefficient of Variation 31 |
| Moderate Renal Impairment | Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib | 39.47 nanogram*hour per milliliter | Geometric Coefficient of Variation 47 |
| Severe Renal Impairment | Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib | 81.17 nanogram*hour per milliliter | Geometric Coefficient of Variation 36 |
90% CI: [83.85, 167.7]
90% CI: [99.53, 195.06]
90% CI: [202.66, 405.33]
Primary
Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
Cmax was defined as the maximum observed plasma concentration of talazoparib.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | 8.609 nanogram per milliliter | Geometric Coefficient of Variation 35 |
| Mild Renal Impairment | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | 9.568 nanogram per milliliter | Geometric Coefficient of Variation 58 |
| Moderate Renal Impairment | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | 11.33 nanogram per milliliter | Geometric Coefficient of Variation 45 |
| Severe Renal Impairment | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | 16.30 nanogram per milliliter | Geometric Coefficient of Variation 34 |
90% CI: [74.4, 166.01]
90% CI: [89.12, 194.25]
90% CI: [126.74, 282.8]
Primary
Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | 2.570 nanogram per milliliter | Geometric Coefficient of Variation 42 |
| Mild Renal Impairment | Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | 3.019 nanogram per milliliter | Geometric Coefficient of Variation 47 |
| Moderate Renal Impairment | Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | 3.295 nanogram per milliliter | Geometric Coefficient of Variation 48 |
| Severe Renal Impairment | Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | 5.296 nanogram per milliliter | Geometric Coefficient of Variation 30 |
90% CI: [79.74, 172.99]
90% CI: [88.05, 186.72]
90% CI: [139.91, 303.51]
Secondary
Change From Baseline in Body Weight of Participants
Time frame: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)
Population: Safety analysis included all participants who received any amount of talazoparib. Here, number analyzed signifies participants evaluable for specific rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Renal Function | Change From Baseline in Body Weight of Participants | Change at Day 15 | -0.17 kilograms | Standard Deviation 1.707 |
| Normal Renal Function | Change From Baseline in Body Weight of Participants | Baseline | 68.60 kilograms | Standard Deviation 14.651 |
| Normal Renal Function | Change From Baseline in Body Weight of Participants | Change at Day 22 | -0.43 kilograms | Standard Deviation 2.366 |
| Normal Renal Function | Change From Baseline in Body Weight of Participants | Change at Day 8 | 0.16 kilograms | Standard Deviation 1.03 |
| Normal Renal Function | Change From Baseline in Body Weight of Participants | Change at Day 52 | 4.90 kilograms | — |
| Mild Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 15 | -0.38 kilograms | Standard Deviation 1.045 |
| Mild Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 8 | -0.62 kilograms | Standard Deviation 0.424 |
| Mild Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 22 | -0.78 kilograms | Standard Deviation 1.058 |
| Mild Renal Impairment | Change From Baseline in Body Weight of Participants | Baseline | 69.12 kilograms | Standard Deviation 14.914 |
| Mild Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 52 | 0.70 kilograms | — |
| Moderate Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 52 | -0.67 kilograms | Standard Deviation 2.122 |
| Moderate Renal Impairment | Change From Baseline in Body Weight of Participants | Baseline | 85.84 kilograms | Standard Deviation 20.221 |
| Moderate Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 8 | -0.26 kilograms | Standard Deviation 0.912 |
| Moderate Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 15 | 0.05 kilograms | Standard Deviation 1.59 |
| Moderate Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 22 | 0.04 kilograms | Standard Deviation 1.722 |
| Severe Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 52 | 2.88 kilograms | Standard Deviation 14.597 |
| Severe Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 22 | -0.75 kilograms | Standard Deviation 3.189 |
| Severe Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 8 | -0.26 kilograms | Standard Deviation 1.834 |
| Severe Renal Impairment | Change From Baseline in Body Weight of Participants | Baseline | 66.79 kilograms | Standard Deviation 13.277 |
| Severe Renal Impairment | Change From Baseline in Body Weight of Participants | Change at Day 15 | -0.23 kilograms | Standard Deviation 2.371 |
Secondary
Change From Baseline in Diastolic Blood Pressure (DBP) of Participants
Time frame: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)
Population: Safety analysis included all participants who received any amount of talazoparib. Here, number analyzed signifies participants evaluable for specific rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Renal Function | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 22 | 3.4 mmHg | Standard Deviation 10.5 |
| Normal Renal Function | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 8 | 5.4 mmHg | Standard Deviation 4.48 |
| Normal Renal Function | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 52 | 4.0 mmHg | — |
| Normal Renal Function | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 15 | -0.2 mmHg | Standard Deviation 6.02 |
| Normal Renal Function | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Baseline | 69.8 mmHg | Standard Deviation 7.69 |
| Mild Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 15 | -5.9 mmHg | Standard Deviation 6.62 |
| Mild Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 22 | -4.6 mmHg | Standard Deviation 6.13 |
| Mild Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 52 | -18.0 mmHg | — |
| Mild Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 8 | -4.6 mmHg | Standard Deviation 10.48 |
| Mild Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Baseline | 78.3 mmHg | Standard Deviation 8.38 |
| Moderate Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 15 | 0.4 mmHg | Standard Deviation 8.86 |
| Moderate Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Baseline | 69.8 mmHg | Standard Deviation 5.65 |
| Moderate Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 8 | 2.8 mmHg | Standard Deviation 8.15 |
| Moderate Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 22 | 5.5 mmHg | Standard Deviation 11.95 |
| Moderate Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 52 | 1.0 mmHg | Standard Deviation 6 |
| Severe Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 22 | -4.0 mmHg | Standard Deviation 8.18 |
| Severe Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 8 | -3.4 mmHg | Standard Deviation 9.96 |
| Severe Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Baseline | 74.8 mmHg | Standard Deviation 14.1 |
| Severe Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 15 | -1.1 mmHg | Standard Deviation 11.37 |
| Severe Renal Impairment | Change From Baseline in Diastolic Blood Pressure (DBP) of Participants | Change at Day 52 | -1.0 mmHg | Standard Deviation 20.98 |
Secondary
Change From Baseline in Heart Rate of Participants
Heart rate was measured in terms of beats per minute.
Time frame: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)
Population: Safety analysis included all participants who received any amount of talazoparib. Here, number analyzed signifies participants evaluable for specific rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Renal Function | Change From Baseline in Heart Rate of Participants | Change at Day 22 | -1.7 beats per minute | Standard Deviation 11.86 |
| Normal Renal Function | Change From Baseline in Heart Rate of Participants | Change at Day 8 | 3.3 beats per minute | Standard Deviation 9.18 |
| Normal Renal Function | Change From Baseline in Heart Rate of Participants | Change at Day 52 | -10.0 beats per minute | — |
| Normal Renal Function | Change From Baseline in Heart Rate of Participants | Change at Day 15 | 3.7 beats per minute | Standard Deviation 8.6 |
| Normal Renal Function | Change From Baseline in Heart Rate of Participants | Baseline | 85.2 beats per minute | Standard Deviation 11.23 |
| Mild Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 15 | -4.3 beats per minute | Standard Deviation 10.56 |
| Mild Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 22 | -8.0 beats per minute | Standard Deviation 5.85 |
| Mild Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 52 | -15.0 beats per minute | — |
| Mild Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 8 | -0.2 beats per minute | Standard Deviation 8.74 |
| Mild Renal Impairment | Change From Baseline in Heart Rate of Participants | Baseline | 81.6 beats per minute | Standard Deviation 21.86 |
| Moderate Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 15 | -1.8 beats per minute | Standard Deviation 11.11 |
| Moderate Renal Impairment | Change From Baseline in Heart Rate of Participants | Baseline | 80.1 beats per minute | Standard Deviation 11.54 |
| Moderate Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 8 | 2.1 beats per minute | Standard Deviation 12.22 |
| Moderate Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 22 | -0.9 beats per minute | Standard Deviation 10.38 |
| Moderate Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 52 | 1.7 beats per minute | Standard Deviation 2.52 |
| Severe Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 22 | -7.4 beats per minute | Standard Deviation 20.56 |
| Severe Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 8 | -4.6 beats per minute | Standard Deviation 23.4 |
| Severe Renal Impairment | Change From Baseline in Heart Rate of Participants | Baseline | 77.4 beats per minute | Standard Deviation 23.34 |
| Severe Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 15 | -1.9 beats per minute | Standard Deviation 16.07 |
| Severe Renal Impairment | Change From Baseline in Heart Rate of Participants | Change at Day 52 | -0.8 beats per minute | Standard Deviation 8.04 |
Secondary
Change From Baseline in Respiratory Rate of Participants
Respiratory rate was measured in terms of breaths per minute.
Time frame: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)
Population: Safety analysis included all participants who received any amount of talazoparib. Here, number analyzed signifies participants evaluable for specific rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Renal Function | Change From Baseline in Respiratory Rate of Participants | Change at Day 22 | 0.2 breaths per minute | Standard Deviation 0.67 |
| Normal Renal Function | Change From Baseline in Respiratory Rate of Participants | Change at Day 8 | 0.2 breaths per minute | Standard Deviation 0.67 |
| Normal Renal Function | Change From Baseline in Respiratory Rate of Participants | Change at Day 52 | 0.0 breaths per minute | — |
| Normal Renal Function | Change From Baseline in Respiratory Rate of Participants | Change at Day 15 | 0.9 breaths per minute | Standard Deviation 1.05 |
| Normal Renal Function | Change From Baseline in Respiratory Rate of Participants | Baseline | 17.6 breaths per minute | Standard Deviation 0.88 |
| Mild Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 15 | -0.8 breaths per minute | Standard Deviation 1.72 |
| Mild Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 22 | -1.1 breaths per minute | Standard Deviation 1.36 |
| Mild Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 52 | 1.0 breaths per minute | — |
| Mild Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 8 | -0.3 breaths per minute | Standard Deviation 1.58 |
| Mild Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Baseline | 18.4 breaths per minute | Standard Deviation 0.88 |
| Moderate Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 15 | 0.0 breaths per minute | Standard Deviation 2.14 |
| Moderate Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Baseline | 18.3 breaths per minute | Standard Deviation 1.67 |
| Moderate Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 8 | 0.5 breaths per minute | Standard Deviation 2.07 |
| Moderate Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 22 | 0.6 breaths per minute | Standard Deviation 2.45 |
| Moderate Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 52 | 1.3 breaths per minute | Standard Deviation 2.31 |
| Severe Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 22 | -1.0 breaths per minute | Standard Deviation 4 |
| Severe Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 8 | -0.8 breaths per minute | Standard Deviation 4.4 |
| Severe Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Baseline | 17.8 breaths per minute | Standard Deviation 4.71 |
| Severe Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 15 | -1.0 breaths per minute | Standard Deviation 4 |
| Severe Renal Impairment | Change From Baseline in Respiratory Rate of Participants | Change at Day 52 | -1.4 breaths per minute | Standard Deviation 6.31 |
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) of Participants
Time frame: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)
Population: Safety analysis included all participants who received any amount of talazoparib. Here, number analyzed signifies participants evaluable for specific rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Renal Function | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 22 | 7.3 millimeters of mercury (mmHg) | Standard Deviation 15.72 |
| Normal Renal Function | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 8 | 9.0 millimeters of mercury (mmHg) | Standard Deviation 17.29 |
| Normal Renal Function | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 52 | -3.0 millimeters of mercury (mmHg) | — |
| Normal Renal Function | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 15 | 1.9 millimeters of mercury (mmHg) | Standard Deviation 13.48 |
| Normal Renal Function | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Baseline | 115.4 millimeters of mercury (mmHg) | Standard Deviation 13.19 |
| Mild Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 15 | -6.8 millimeters of mercury (mmHg) | Standard Deviation 7.03 |
| Mild Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 22 | -7.3 millimeters of mercury (mmHg) | Standard Deviation 12.66 |
| Mild Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 52 | -42.0 millimeters of mercury (mmHg) | — |
| Mild Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 8 | -6.7 millimeters of mercury (mmHg) | Standard Deviation 18.28 |
| Mild Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Baseline | 124.3 millimeters of mercury (mmHg) | Standard Deviation 11.55 |
| Moderate Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 15 | -5.6 millimeters of mercury (mmHg) | Standard Deviation 4.87 |
| Moderate Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Baseline | 123.8 millimeters of mercury (mmHg) | Standard Deviation 11.63 |
| Moderate Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 8 | -2.5 millimeters of mercury (mmHg) | Standard Deviation 8.5 |
| Moderate Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 22 | 0.1 millimeters of mercury (mmHg) | Standard Deviation 7.9 |
| Moderate Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 52 | 4.3 millimeters of mercury (mmHg) | Standard Deviation 9.02 |
| Severe Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 22 | 1.0 millimeters of mercury (mmHg) | Standard Deviation 12.02 |
| Severe Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 8 | -7.3 millimeters of mercury (mmHg) | Standard Deviation 11.29 |
| Severe Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Baseline | 133.6 millimeters of mercury (mmHg) | Standard Deviation 17.25 |
| Severe Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 15 | -2.9 millimeters of mercury (mmHg) | Standard Deviation 18.05 |
| Severe Renal Impairment | Change From Baseline in Systolic Blood Pressure (SBP) of Participants | Change at Day 52 | -10.8 millimeters of mercury (mmHg) | Standard Deviation 18.75 |
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.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 and Day 22
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Accumulation Ratio (Rac) of AUC (0-24) | 5.418 ratio | Geometric Coefficient of Variation 59 |
| Mild Renal Impairment | Multiple Dose: Accumulation Ratio (Rac) of AUC (0-24) | 4.510 ratio | Geometric Coefficient of Variation 42 |
| Moderate Renal Impairment | Multiple Dose: Accumulation Ratio (Rac) of AUC (0-24) | 6.239 ratio | Geometric Coefficient of Variation 38 |
| Severe Renal Impairment | Multiple Dose: Accumulation Ratio (Rac) of AUC (0-24) | 8.330 ratio | Geometric Coefficient of Variation 36 |
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.
Time frame: 0 to 24 hours on Day 22
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Amount of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) | 0.2584 milligram | Geometric Coefficient of Variation 23 |
| Mild Renal Impairment | Multiple Dose: Amount of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) | 0.2321 milligram | Geometric Coefficient of Variation 20 |
| Moderate Renal Impairment | Multiple Dose: Amount of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) | 0.1637 milligram | Geometric Coefficient of Variation 54 |
| Severe Renal Impairment | Multiple Dose: Amount of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) | 0.2005 milligram | Geometric Coefficient of Variation 34 |
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.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Apparent Oral Clearance (CL/F) of Talazoparib | 5.270 liters per hour | Geometric Coefficient of Variation 27 |
| Mild Renal Impairment | Multiple Dose: Apparent Oral Clearance (CL/F) of Talazoparib | 4.698 liters per hour | Geometric Coefficient of Variation 40 |
| Moderate Renal Impairment | Multiple Dose: Apparent Oral Clearance (CL/F) of Talazoparib | 3.687 liters per hour | Geometric Coefficient of Variation 45 |
| Severe Renal Impairment | Multiple Dose: Apparent Oral Clearance (CL/F) of Talazoparib | 2.000 liters per hour | Geometric Coefficient of Variation 30 |
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.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22
Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | 29.85 ratio | Geometric Coefficient of Variation 24 |
| Mild Renal Impairment | Multiple Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | 31.54 ratio | Geometric Coefficient of Variation 10 |
| Moderate Renal Impairment | Multiple Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | 29.09 ratio | Geometric Coefficient of Variation 9 |
| Severe Renal Impairment | Multiple Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | 32.49 ratio | Geometric Coefficient of Variation 30 |
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.
Time frame: 0 to 24 hours on Day 22
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24 %) of Talazoparib at Day 22 | 51.66 percentage of dose | Geometric Coefficient of Variation 23 |
| Mild Renal Impairment | Multiple Dose: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24 %) of Talazoparib at Day 22 | 46.40 percentage of dose | Geometric Coefficient of Variation 20 |
| Moderate Renal Impairment | Multiple Dose: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24 %) of Talazoparib at Day 22 | 32.78 percentage of dose | Geometric Coefficient of Variation 54 |
| Severe Renal Impairment | Multiple Dose: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24 %) of Talazoparib at Day 22 | 40.07 percentage of dose | Geometric Coefficient of Variation 34 |
Secondary
Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib
Ctrough was defined as plasma trough (predose) concentration of talazoparib.
Time frame: Predose on Day 22
Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib | 2.172 nanogram per milliliter | Geometric Coefficient of Variation 34 |
| Mild Renal Impairment | Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib | 2.680 nanogram per milliliter | Geometric Coefficient of Variation 52 |
| Moderate Renal Impairment | Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib | 3.893 nanogram per milliliter | Geometric Coefficient of Variation 45 |
| Severe Renal Impairment | Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib | 7.917 nanogram per milliliter | Geometric Coefficient of Variation 44 |
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.
Time frame: 0 to 24 hours on Day 22
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Renal Clearance (CLr) of Talazoparib at Day 22 | 2.738 liters per hour | Geometric Coefficient of Variation 37 |
| Mild Renal Impairment | Multiple Dose: Renal Clearance (CLr) of Talazoparib at Day 22 | 2.180 liters per hour | Geometric Coefficient of Variation 57 |
| Moderate Renal Impairment | Multiple Dose: Renal Clearance (CLr) of Talazoparib at Day 22 | 1.330 liters per hour | Geometric Coefficient of Variation 97 |
| Severe Renal Impairment | Multiple Dose: Renal Clearance (CLr) of Talazoparib at Day 22 | 0.7094 liters per hour | Geometric Coefficient of Variation 35 |
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.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Renal Function | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | 1.500 hours |
| Mild Renal Impairment | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | 2.000 hours |
| Moderate Renal Impairment | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | 1.490 hours |
| Severe Renal Impairment | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | 3.880 hours |
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.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22
Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Multiple Dose: Unbound Apparent Oral Clearance (CLu/F) of Talazoparib | 17.66 liters per hour | Geometric Coefficient of Variation 32 |
| Mild Renal Impairment | Multiple Dose: Unbound Apparent Oral Clearance (CLu/F) of Talazoparib | 14.89 liters per hour | Geometric Coefficient of Variation 31 |
| Moderate Renal Impairment | Multiple Dose: Unbound Apparent Oral Clearance (CLu/F) of Talazoparib | 12.68 liters per hour | Geometric Coefficient of Variation 47 |
| Severe Renal Impairment | Multiple Dose: Unbound Apparent Oral Clearance (CLu/F) of Talazoparib | 6.614 liters per hour | Geometric Coefficient of Variation 36 |
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.
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Population: Safety analysis included all participants who received any amount of talazoparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Normal Renal Function | Number of Participants With Abnormalities in Physical Examination | 0 Participants |
| Mild Renal Impairment | Number of Participants With Abnormalities in Physical Examination | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Abnormalities in Physical Examination | 0 Participants |
| Severe Renal Impairment | Number of Participants With Abnormalities in Physical Examination | 0 Participants |
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.
Time frame: Baseline, Safety follow up (Day 52)
Population: Safety analysis included all participants who received any amount of talazoparib. Here, Number Analyzed signifies participants who were evaluable at specific rows.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Normal Renal Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 1 | 4 Participants |
| Normal Renal Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 2 | 0 Participants |
| Normal Renal Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 3 | 0 Participants |
| Normal Renal Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 1 | 1 Participants |
| Normal Renal Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 0 | 3 Participants |
| Normal Renal Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 3 | 0 Participants |
| Normal Renal Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 4 | 0 Participants |
| Normal Renal Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 4 | 0 Participants |
| Normal Renal Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 2 | 2 Participants |
| Normal Renal Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 0 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 2 | 1 Participants |
| Mild Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 0 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 1 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 1 | 7 Participants |
| Mild Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 0 | 2 Participants |
| Mild Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 2 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 3 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 3 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 4 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 4 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 2 | 2 Participants |
| Moderate Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 0 | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 1 | 5 Participants |
| Moderate Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 3 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 4 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 0 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 1 | 3 Participants |
| Moderate Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 2 | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 3 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 4 | 0 Participants |
| Severe Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 0 | 1 Participants |
| Severe Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 2 | 1 Participants |
| Severe Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 3 | 0 Participants |
| Severe Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 2 | 3 Participants |
| Severe Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 4 | 1 Participants |
| Severe Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 3 | 1 Participants |
| Severe Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 1 | 4 Participants |
| Severe Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 1 | 2 Participants |
| Severe Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 52 | ECOG: 0 | 0 Participants |
| Severe Renal Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline | ECOG: 4 | 0 Participants |
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.
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Population: Safety analysis included all participants who received any amount of talazoparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Normal Renal Function | Number of Participants With Electrocardiogram (ECG) Abnormalities | 2 Participants |
| Mild Renal Impairment | Number of Participants With Electrocardiogram (ECG) Abnormalities | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Electrocardiogram (ECG) Abnormalities | 5 Participants |
| Severe Renal Impairment | Number of Participants With Electrocardiogram (ECG) Abnormalities | 3 Participants |
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.
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Population: Safety analysis included all participants who received any amount of talazoparib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Normal Renal Function | Number of Participants With Laboratory Abnormalities | Grade 2 | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Abnormalities | Grade 1 | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Abnormalities | Grade 4 | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Abnormalities | Grade 3 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 1 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 2 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 3 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 4 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 1 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 3 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 2 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 4 | 0 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 2 | 0 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 3 | 0 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 4 | 0 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Abnormalities | Grade 1 | 0 Participants |
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.
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Population: Safety analysis included all participants who received any amount of talazoparib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Normal Renal Function | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 7 Participants |
| Normal Renal Function | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Mild Renal Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Mild Renal Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 8 Participants |
| Moderate Renal Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 8 Participants |
| Moderate Renal Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Severe Renal Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 7 Participants |
| Severe Renal Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
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.
Time frame: 0 to 24 hours on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Single Dose: Amount of Talazoparib Excreted Unchanged in Urine From Time 0 to 24 Hours (Ae 0-24) | 0.05452 milligram | Geometric Coefficient of Variation 51 |
| Mild Renal Impairment | Single Dose: Amount of Talazoparib Excreted Unchanged in Urine From Time 0 to 24 Hours (Ae 0-24) | 0.05430 milligram | Geometric Coefficient of Variation 38 |
| Moderate Renal Impairment | Single Dose: Amount of Talazoparib Excreted Unchanged in Urine From Time 0 to 24 Hours (Ae 0-24) | 0.02765 milligram | Geometric Coefficient of Variation 59 |
| Severe Renal Impairment | Single Dose: Amount of Talazoparib Excreted Unchanged in Urine From Time 0 to 24 Hours (Ae 0-24) | 0.01901 milligram | Geometric Coefficient of Variation 78 |
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.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | 17.51 nanogram*hour per milliliter | Geometric Coefficient of Variation 59 |
| Mild Renal Impairment | Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | 23.60 nanogram*hour per milliliter | Geometric Coefficient of Variation 47 |
| Moderate Renal Impairment | Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | 21.96 nanogram*hour per milliliter | Geometric Coefficient of Variation 40 |
| Severe Renal Impairment | Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib | 29.98 nanogram*hour per milliliter | Geometric Coefficient of Variation 25 |
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.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib | 5.555 nanogram*hour per milliliter | Geometric Coefficient of Variation 81 |
| Mild Renal Impairment | Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib | 7.956 nanogram*hour per milliliter | Geometric Coefficient of Variation 35 |
| Moderate Renal Impairment | Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib | 6.262 nanogram*hour per milliliter | Geometric Coefficient of Variation 39 |
| Severe Renal Impairment | Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib | 10.95 nanogram*hour per milliliter | Geometric Coefficient of Variation 28 |
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.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | 31.74 ratio | Geometric Coefficient of Variation 22 |
| Mild Renal Impairment | Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | 33.71 ratio | Geometric Coefficient of Variation 14 |
| Moderate Renal Impairment | Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | 28.77 ratio | Geometric Coefficient of Variation 7 |
| Severe Renal Impairment | Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib | 33.91 ratio | Geometric Coefficient of Variation 19 |
Secondary
Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
Cmax was defined as the maximum observed plasma concentration of talazoparib.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | 2.133 nanogram per milliliter | Geometric Coefficient of Variation 56 |
| Mild Renal Impairment | Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | 2.422 nanogram per milliliter | Geometric Coefficient of Variation 29 |
| Moderate Renal Impairment | Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | 2.862 nanogram per milliliter | Geometric Coefficient of Variation 75 |
| Severe Renal Impairment | Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | 2.624 nanogram per milliliter | Geometric Coefficient of Variation 66 |
Secondary
Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | 0.6772 nanogram per milliliter | Geometric Coefficient of Variation 67 |
| Mild Renal Impairment | Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | 0.8168 nanogram per milliliter | Geometric Coefficient of Variation 62 |
| Moderate Renal Impairment | Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | 0.8229 nanogram per milliliter | Geometric Coefficient of Variation 70 |
| Severe Renal Impairment | Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib | 1.031 nanogram per milliliter | Geometric Coefficient of Variation 43 |
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.
Time frame: 0 to 24 hours on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Single Dose: Percentage of Dose of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) at Day 1 | 10.91 percentage of dose | Geometric Coefficient of Variation 51 |
| Mild Renal Impairment | Single Dose: Percentage of Dose of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) at Day 1 | 10.85 percentage of dose | Geometric Coefficient of Variation 38 |
| Moderate Renal Impairment | Single Dose: Percentage of Dose of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) at Day 1 | 5.532 percentage of dose | Geometric Coefficient of Variation 59 |
| Severe Renal Impairment | Single Dose: Percentage of Dose of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) at Day 1 | 3.795 percentage of dose | Geometric Coefficient of Variation 78 |
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.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Renal Function | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | 1.515 hours |
| Mild Renal Impairment | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | 1.000 hours |
| Moderate Renal Impairment | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | 0.9900 hours |
| Severe Renal Impairment | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | 1.830 hours |