Advanced Solid Tumors
Conditions
Brief summary
This is a study in patients with advanced solid tumors for the investigation of P-gp inhibition and induction on the PK of talazoparib.
Detailed description
Subjects participating in this study with no clinically significant toxicities and no disease progression may be eligible to continue treatment on a separate extension protocol (MDV3800-13).
Interventions
DRUGTalazoparib
Arm A: 0.5 mg oral dose Arm B: 1 mg oral dose
DRUGItraconazole
100 mg oral dose
DRUGRifampin
600 mg oral dose
Sponsors
Medivation, Inc.
Pfizer
Study design
Allocation
NON_RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Arm A: At least 18 years of age and \<65 years of age (at the time point of consent) and willing and able to provide informed consent. Arm B: At least 18 years of age (at the time point of consent) and willing and able to provide informed consent. 2. Histologically confirmed advanced solid tumor (limited to platinum-resistant ovarian carcinoma, cervical adenocarcinoma, small cell lung carcinoma or triple-negative breast cancer) judged by the Investigator to not be appropriate for standard therapy. 3. ECOG performance status ≤ 2 at screening and at time of enrollment. 4. Expected life expectancy of ≥ 3 months. 5. Able to swallow the study drug and comply with study requirements. 6. Female subjects may be enrolled if they are considered not of childbearing potential, or who are post-menopausal, or are of childbearing potential using a highly effective form of contraceptive, and female subjects should not donate eggs from the time point of investigational medicinal product (IMP) administration until at least 45 days thereafter. 7. Males with partners of childbearing potential may be enrolled if they use a condom when having sex with a pregnant woman or with a woman of childbearing potential, and do not donate sperm from the time point of study drug administration until at least 105 days thereafter, and males should not donate sperm from the time point of study drug administration until at least 105 days thereafter. 8. Female subjects must not be breastfeeding at screening and during the study participation until 45 days after the last dose of the study drug. 9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Exclusion criteria
1. Treatment within 14 days or 5 half lives prior to dosing with any type of systemic anticancer therapy or any investigational agent, whichever is longer 2. Major surgery within 8 weeks before screening. 3. Serious accompanying disorder or impaired organ function. 4. Symptomatic or impending spinal cord compression or cauda equina syndrome. 5. Non-healing wound, ulcer, or bone fracture, not including a pathological bone fracture caused by a pre-existent pathological bone lesion. 6. Known myelodysplastic syndrome. 7. Subjects with the following serologies should be excluded: HBsAg+ or anti-HBc+;HCV+; HIV+. 8. Serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol. 9. Gastrointestinal disorder affecting absorption. 10. Known hypersensitivity to any of the talazoparib capsule components. 11. Any condition or reason that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator or Sponsor (e.g. non-compliance, excessive alcohol consumption, intake of drugs of abuse unless these drugs are medically indicated \[e.g. opiates for pain relief\].
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole | T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23 | T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Itraconazole | T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23 | T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf) of Talazoparib: Alone and in Combination With Itraconazole | T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23 | T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID. |
| Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Rifampin | T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25 | T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Rifampin | T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25 | T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Talazoparib: Alone and in Combination With Rifampin | T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25 | T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Itraconazole | T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23 | T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID. |
| Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Itraconazole | T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23 | Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half. T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID. |
| Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Itraconazole | T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23 | Clearance of talazoparib was measure of the rate at which it was metabolized or eliminated by normal biological processes. T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID. |
| Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Itraconazole | T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23 | Apparent volume of distribution was defined as the theoretical volume in which the total amount of talazoparib would need to be uniformly distributed to produce its desired plasma concentration. T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID. |
| Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Rifampin | T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25 | T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD. |
| Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Rifampin | T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25 | Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half. T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD. |
| Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Rifampin | T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25 | Apparent volume of distribution was defined as the theoretical volume in which the total amount of talazoparib would need to be uniformly distributed to produce its desired plasma concentration. T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD. |
| Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Rifampin | T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25 | Clearance of talazoparib was measure of the rate at which it was metabolized or eliminated by normal biological processes. T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline up to end of study (up to 61 days) | An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An 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 or incapacity, congenital anomaly. A TEAE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pre-treatment state. AEs included both serious and non-serious adverse events. |
| Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters | Baseline up to end of study (up to 61 days) | Chemistry:(sodium135-146,potassium3.5-5.5,chloride95-109,glucose3.3-5.5,urea2.8-7.2,calcium2.2-2.65,phosphate0.8-1.45,triglyceride0.4-1.7,cholesterol2.6-5.2)millimoles/L, (bilirubin\[direct0-3,total2-21\],creatinine53- 110)micromole/L, (albumin35-52,protein65-83)g/L,(alkaline phosphatase30-120, aspartate amino\[A\]transferase\[T\]4-46, alanine AT4-49, lactic acid dehydrogenase200-460, gammaglutamylT7-50,creatinine kinase24-170)U/L. Hematology: hemoglobin(Hb)120-177, hematocrit0.35-0.49L/L, RBC4-5.9T/L, (platelet150- 400,WBC4-10,basophil\<0.10,eosinophil\<0.40, neutrophil1.50-7.00,monocyte\<1.20,lymphocyte1.0 -3.70)G/L. Urine:(glucose,protein,ketone,Hb:negative/positive), specific gravity1.010-1.030g/cm\^3, pH4.8-7.8, pale yellow-deep amber, microscopy\[WBC0-5,leukocyte0-5,Hb0-3,cast0-1,bacteria0-500,epithelial0-6\])Pcs/area. Coagulation:(activated partial thromboplastine time25-43,prothrombin time13.7-15.6) seconds,international normalized ratio0.89-1.1. Investigator judged clinical significance. |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs | Baseline up to end of study (up to 61 days) | Vital sign abnormalities: a) systolic blood pressure (SBP): 1) minimum less than (\<) 90 millimeter of mercury (mmHg), 2) change from baseline maximum decrease greater than equal to (\>=) 30 mmHg, 3) change from baseline maximum increase \>=30 mmHg; b) diastolic blood pressure (DBP): 1) minimum \<50 mmHg, 2) change from baseline maximum decrease \>=20 mmHg, 3) change from baseline maximum increase \>=20 mmHg; c) supine pulse rate: 1) minimum \<40 beats per minute (bpm), 2) maximum \>120 bpm; d) standing pulse rate: 1) minimum \<40 bpm and 2) maximum \>140 bpm. Clinical significance of vital signs abnormalities was judged by investigator. |
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | Baseline up to end of study (up to 61 days) | ECG abnormalities: a) QT Interval: new absolute values greater than (\>) 450, \>480, \>500 milliseconds (msec), increase from baseline \>30 and \>60 msec, b) QT interval using Fridericia's correction (QTcF) Interval: new absolute values \>450, \>480, \>500 msec, increase from baseline \>30 and \> 60 msec, c) Heart rate: increase from baseline \>25 percentage (%) and to a value \>100 bpm, decrease from baseline \>25% and to a value \<50 bpm, d) PR Interval: increase from baseline \> 25% and to a value \>200 msec, e) QRS duration: increase from baseline \> 25% and to a value \>100 msec. Clinical significance of ECG abnormalities was judged by investigator. |
| Number of Participants With Clinically Significant Physical Examination Findings | Baseline up to end of study (up to 61 days) | Physical examination included examination of abdomen, cardiovascular, eyes, ears, nose, throat, general appearance, head, neck, thyroid, lymph nodes, musculoskeletal, neurological, skin / subcutaneous tissue, thorax / lungs, abdomen including spleen size, breasts (female only) and respiratory. Clinical significance of physical examination was judged by investigator. |
Countries
Hungary, Moldova, Poland, Russia
Participant flow
Pre-assignment details
Study was conducted in 4 countries from 07-Nov-2016 to 18 Dec 2017.
Participants by arm
| Arm | Count |
|---|---|
| A: Talazoparib 0.5 mg + Itraconazole 100 mg BID Participants received a single oral dose of talazoparib 0.5 mg on Day 1, which was followed by a wash out of 14 days in Period 1. Then in Period 2 participants received oral dose of itraconazole 200 mg (100 mg BID) from Day 16 to Day 36 and a single oral dose of talazoparib 0.5 mg on Day 23. Participants were followed up to 23 days after last dose of study drug. | 19 |
| B: Talazoparib 1 mg + Rifampin 600 mg QD Participants received a single oral dose of talazoparib 1.0 mg on Day 1, which was followed by a wash out of 14 days in Period 1. Then in Period 2 participants received oral dose of rifampin 600 mg QD from Day 16 to Day 38 and a single oral dose of talazoparib 1.0 mg on Day 25. Participants were followed up to 23 days after last dose of study drug. | 17 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 (15 Days) | Adverse Event | 1 | 0 |
| Period 1 (15 Days) | Death | 1 | 0 |
| Period 2 (Arm A:21 Days; Arm B:23 Days) | Adverse Event | 2 | 2 |
| Period 2 (Arm A:21 Days; Arm B:23 Days) | Death | 1 | 0 |
Baseline characteristics
| Characteristic | A: Talazoparib 0.5 mg + Itraconazole 100 mg BID | B: Talazoparib 1 mg + Rifampin 600 mg QD | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 13 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 4 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 17 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 17 Participants | 36 Participants |
| Sex: Female, Male Female | 17 Participants | 13 Participants | 30 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 19 | 0 / 16 | 1 / 15 | 0 / 17 | 0 / 17 | 0 / 15 |
| other Total, other adverse events | 12 / 19 | 3 / 16 | 5 / 15 | 6 / 17 | 9 / 17 | 5 / 15 |
| serious Total, serious adverse events | 3 / 19 | 0 / 16 | 1 / 15 | 0 / 17 | 2 / 17 | 0 / 15 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Talazoparib: Alone and in Combination With Rifampin
T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD.
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Talazoparib: Alone and in Combination With Rifampin | 209521.62 hr*pg/mL | Geometric Coefficient of Variation 34 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Talazoparib: Alone and in Combination With Rifampin | 194307.67 hr*pg/mL | Geometric Coefficient of Variation 36 |
Comparison: CI: 90% CI on geometric LS mean ratio (Test/Reference), test is talazoparib in Combination with rifampin and reference is talazoparib alone. Statistical data was calculated by using ANOVA.90% CI: [94.02, 110.74]
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Itraconazole
T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID.
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Itraconazole | 98532.30 Hour*picogram per milliliter (hr*pg/mL) | Geometric Coefficient of Variation 38 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Itraconazole | 145944.59 Hour*picogram per milliliter (hr*pg/mL) | Geometric Coefficient of Variation 38 |
Comparison: CI: 90% CI on geometric LS mean ratio (Test/Reference), test is talazoparib in combination with itraconazole and reference is talazoparib alone. Statistical data was calculated by using ANOVA.90% CI: [136.47, 166.43]
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Rifampin
T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD.
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Rifampin | 196631.34 hr*pg/mL | Geometric Coefficient of Variation 32 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Rifampin | 196100.69 hr*pg/mL | Geometric Coefficient of Variation 33 |
Comparison: CI: 90% CI on geometric LS mean ratio (Test/Reference), test is talazoparib in Combination with rifampin and reference is talazoparib alone. Statistical data was calculated by using ANOVA.90% CI: [98.04, 113.24]
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf) of Talazoparib: Alone and in Combination With Itraconazole
T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID.
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters. Here, Overall number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf) of Talazoparib: Alone and in Combination With Itraconazole | 109762.10 hr*pg/mL | Geometric Coefficient of Variation 42 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf) of Talazoparib: Alone and in Combination With Itraconazole | 151919.63 hr*pg/mL | Geometric Coefficient of Variation 36 |
Comparison: CI: 90% CI on geometric LS mean ratio (Test/Reference), test is talazoparib in combination with itraconazole and reference is talazoparib alone. Statistical data was calculated by using ANOVA.90% CI: [137.58, 177.42]
Primary
Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole
T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID.
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Population: Pharmacokinetic (PK) analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole | 2092.00 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 50 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole | 2936.82 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 56 |
Comparison: Confidence interval (CI): 90 percent (%) CI on geometric least squares (LS) mean ratio (Test/Reference), test is talazoparib in combination with itraconazole and reference is talazoparib alone. Statistical data was calculated by using analysis of variance (ANOVA)90% CI: [113.26, 172.87]
Primary
Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Rifampin
T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD.
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Rifampin | 6007.01 pg/mL | Geometric Coefficient of Variation 53 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Rifampin | 8336.83 pg/mL | Geometric Coefficient of Variation 71 |
Comparison: CI: 90% CI on geometric LS mean ratio (Test/Reference), test is talazoparib in combination with rifampin and reference is talazoparib alone. Statistical data was calculated by using ANOVA.90% CI: [103.2, 180.87]
Secondary
Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Itraconazole
Clearance of talazoparib was measure of the rate at which it was metabolized or eliminated by normal biological processes. T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID.
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Itraconazole | 4.55 Liter per hour | Geometric Coefficient of Variation 42 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Itraconazole | 3.29 Liter per hour | Geometric Coefficient of Variation 36 |
Secondary
Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Rifampin
Clearance of talazoparib was measure of the rate at which it was metabolized or eliminated by normal biological processes. T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD.
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Rifampin | 4.77 Liter per hour | Geometric Coefficient of Variation 34 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Rifampin | 5.15 Liter per hour | Geometric Coefficient of Variation 36 |
Secondary
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Itraconazole
Apparent volume of distribution was defined as the theoretical volume in which the total amount of talazoparib would need to be uniformly distributed to produce its desired plasma concentration. T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID.
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Itraconazole | 644.81 Liter | Geometric Coefficient of Variation 42 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Itraconazole | 552.01 Liter | Geometric Coefficient of Variation 27 |
Secondary
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Rifampin
Apparent volume of distribution was defined as the theoretical volume in which the total amount of talazoparib would need to be uniformly distributed to produce its desired plasma concentration. T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD.
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Rifampin | 623.89 Liter | Geometric Coefficient of Variation 30 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Rifampin | 588.14 Liter | Geometric Coefficient of Variation 33 |
Secondary
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)
ECG abnormalities: a) QT Interval: new absolute values greater than (\>) 450, \>480, \>500 milliseconds (msec), increase from baseline \>30 and \>60 msec, b) QT interval using Fridericia's correction (QTcF) Interval: new absolute values \>450, \>480, \>500 msec, increase from baseline \>30 and \> 60 msec, c) Heart rate: increase from baseline \>25 percentage (%) and to a value \>100 bpm, decrease from baseline \>25% and to a value \<50 bpm, d) PR Interval: increase from baseline \> 25% and to a value \>200 msec, e) QRS duration: increase from baseline \> 25% and to a value \>100 msec. Clinical significance of ECG abnormalities was judged by investigator.
Time frame: Baseline up to end of study (up to 61 days)
Population: Safety analysis set included all participants who received at least 1 dose of talazoparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib 0.5 mg Alone | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 1 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Talazoparib 1.0 mg Alone | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Rifampin 600 mg QD Alone | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Vital sign abnormalities: a) systolic blood pressure (SBP): 1) minimum less than (\<) 90 millimeter of mercury (mmHg), 2) change from baseline maximum decrease greater than equal to (\>=) 30 mmHg, 3) change from baseline maximum increase \>=30 mmHg; b) diastolic blood pressure (DBP): 1) minimum \<50 mmHg, 2) change from baseline maximum decrease \>=20 mmHg, 3) change from baseline maximum increase \>=20 mmHg; c) supine pulse rate: 1) minimum \<40 beats per minute (bpm), 2) maximum \>120 bpm; d) standing pulse rate: 1) minimum \<40 bpm and 2) maximum \>140 bpm. Clinical significance of vital signs abnormalities was judged by investigator.
Time frame: Baseline up to end of study (up to 61 days)
Population: Safety analysis set included all participants who received at least 1 dose of talazoparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib 0.5 mg Alone | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 1 Participants |
| Talazoparib 1.0 mg Alone | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Rifampin 600 mg QD Alone | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 1 Participants |
Secondary
Number of Participants With Clinically Significant Physical Examination Findings
Physical examination included examination of abdomen, cardiovascular, eyes, ears, nose, throat, general appearance, head, neck, thyroid, lymph nodes, musculoskeletal, neurological, skin / subcutaneous tissue, thorax / lungs, abdomen including spleen size, breasts (female only) and respiratory. Clinical significance of physical examination was judged by investigator.
Time frame: Baseline up to end of study (up to 61 days)
Population: Safety analysis set included all participants who received at least 1 dose of talazoparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib 0.5 mg Alone | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Clinically Significant Physical Examination Findings | 1 Participants |
| Talazoparib 1.0 mg Alone | Number of Participants With Clinically Significant Physical Examination Findings | 1 Participants |
| Rifampin 600 mg QD Alone | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
Secondary
Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters
Chemistry:(sodium135-146,potassium3.5-5.5,chloride95-109,glucose3.3-5.5,urea2.8-7.2,calcium2.2-2.65,phosphate0.8-1.45,triglyceride0.4-1.7,cholesterol2.6-5.2)millimoles/L, (bilirubin\[direct0-3,total2-21\],creatinine53- 110)micromole/L, (albumin35-52,protein65-83)g/L,(alkaline phosphatase30-120, aspartate amino\[A\]transferase\[T\]4-46, alanine AT4-49, lactic acid dehydrogenase200-460, gammaglutamylT7-50,creatinine kinase24-170)U/L. Hematology: hemoglobin(Hb)120-177, hematocrit0.35-0.49L/L, RBC4-5.9T/L, (platelet150- 400,WBC4-10,basophil\<0.10,eosinophil\<0.40, neutrophil1.50-7.00,monocyte\<1.20,lymphocyte1.0 -3.70)G/L. Urine:(glucose,protein,ketone,Hb:negative/positive), specific gravity1.010-1.030g/cm\^3, pH4.8-7.8, pale yellow-deep amber, microscopy\[WBC0-5,leukocyte0-5,Hb0-3,cast0-1,bacteria0-500,epithelial0-6\])Pcs/area. Coagulation:(activated partial thromboplastine time25-43,prothrombin time13.7-15.6) seconds,international normalized ratio0.89-1.1. Investigator judged clinical significance.
Time frame: Baseline up to end of study (up to 61 days)
Population: Safety analysis set included all participants who received at least 1 dose of talazoparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib 0.5 mg Alone | Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters | 3 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters | 0 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters | 1 Participants |
| Talazoparib 1.0 mg Alone | Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters | 2 Participants |
| Rifampin 600 mg QD Alone | Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters | 1 Participants |
| Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD | Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters | 1 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 study treatment without regard to possibility of causal relationship. An 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 or incapacity, congenital anomaly. A TEAE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pre-treatment state. AEs included both serious and non-serious adverse events.
Time frame: Baseline up to end of study (up to 61 days)
Population: Safety analysis set included all participants who received at least 1 dose of talazoparib. Here, 1 participant received 2 doses of rifampin and the SAE anastomotic stenosis took place in the rifampin period. Originally, this SAE was attributed to the talazoparib only period under the assumption that the participant did not receive any dose of rifampin. This SAE was shifted from the talazoparib only period to the rifampin period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 12 Participants |
| Talazoparib 0.5 mg Alone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 3 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 5 Participants |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Talazoparib 1.0 mg Alone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| Talazoparib 1.0 mg Alone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Rifampin 600 mg QD Alone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 9 Participants |
| Rifampin 600 mg QD Alone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
| Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 5 Participants |
| Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Secondary
Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Itraconazole
Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half. T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID.
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Itraconazole | 101.26 Hours | Standard Deviation 26.315 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Itraconazole | 118.47 Hours | Standard Deviation 23.6 |
Secondary
Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Rifampin
Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half. T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD.
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 0.5 mg Alone | Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Rifampin | 92.05 Hours | Standard Deviation 17.679 |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Rifampin | 80.61 Hours | Standard Deviation 16.54 |
Secondary
Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Itraconazole
T1= Time frame for Talazoparib 0.5 mg Alone and T2= time frame for Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID.
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib 0.5 mg Alone | Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Itraconazole | 1.00 Hours |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Itraconazole | 1.02 Hours |
Secondary
Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Rifampin
T3= Time frame for Talazoparib 1.0 mg Alone and T4= time frame for Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD.
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Population: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib 0.5 mg Alone | Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Rifampin | 1.00 Hours |
| Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID | Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Rifampin | 1.00 Hours |