Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Itraconazole

Rifampin

Hydroxyitraconazole

Talazoparib

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Poly(ADP-ribose) Polymerase Inhibitors

Subjects will receive a 0.5 mg talazoparib and 100 mg itraconazole.

Subjects will receive 1 mg talazoparib and 600 mg rifampin.

Arm A: 0.5 mg oral dose Arm B: 1 mg oral dose

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This is a study in patients with advanced solid tumors for the investigation of P-gp inhibition and induction on the PK of talazoparib.

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).

A Study to Evaluate the Effect of Itraconazole and Rifampin on the Pharmacokinetics of Talazoparib in Patients With Advanced Solid Tumors

A PHASE 1 OPEN-LABEL, TWO-ARM,DRUG-DRUG INTERACTION STUDY TO EVALUATE THE EFFECT OF ITRACONAZOLE AND RIFAMPIN ON THE PHARMACOKINETICS OF TALAZOPARIB IN PATIENTS WITH ADVANCED SOLID TUMORS

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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".

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 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".

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 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".

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 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".

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".

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.

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.

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.

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.

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.

Medivation, Inc.

Pfizer

One 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.

Participant received a single oral dose of talazoparib 0.5 mg on Day 1 followed by washout of 14 days in Period 1.

Talazoparib 0.5 mg Alone

Participants those who had received single oral dose of talazoparib 0.5 mg on Day 1 in Period 1, received oral dose of itraconazole 200 mg (100 mg BID) from Day 16 to Day 22 in Period 2.

Itraconazole 100 mg BID Alone

Participants received a single oral dose of talazoparib 0.5 mg on Day 23 and oral dose of itraconazole 200 mg (100 mg BID) from Day 23 onwards to Day 36 in Period 2.

Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID

Participant received a single oral dose of talazoparib 1.0 mg on Day 1 followed by washout of 14 days in Period 1.

Talazoparib 1.0 mg

Participants those who had received a single oral dose of talazoparib 1.0 mg on Day 1 in Period 1, received oral dose of rifampin 600 mg QD from Day 16 to Day 24 in Period 2.

Rifampin 600 mg QD Alone

Participants received a single oral dose of talazoparib 1.0 mg on Day 25 and oral dose of rifampin 600 mg QD from Day 25 onwards to Day 38 in Period 2.

Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD

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.

A: Talazoparib 0.5 mg + Itraconazole 100 mg BID

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.

B: Talazoparib 1 mg + Rifampin 600 mg QD

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Safety population included all participants who had received at least 1 dose of talazoparib.

In this study 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.

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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)

Pharmacokinetic (PK) analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.

Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole

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.

PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Itraconazole

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.

Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf) of Talazoparib: Alone and in Combination With Itraconazole

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.

Talazoparib 1.0 mg Alone

Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Rifampin

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.

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Rifampin

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.

Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Talazoparib: Alone and in Combination With Rifampin

Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Itraconazole

Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Itraconazole

Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Itraconazole

Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Itraconazole

Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Rifampin

Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Rifampin

Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Rifampin

Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Rifampin

SAEs

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.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Safety analysis set included all participants who received at least 1 dose of talazoparib.

Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters

Number of Participants With Clinically Significant Abnormalities in Vital Signs

Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)

Number of Participants With Clinically Significant Physical Examination Findings

Participants received a single oral dose of talazoparib 0.5 milligram (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 twice daily \[BID\]) 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.

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 once daily (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.

Spots Global Cancer Trial Database for A Study to Evaluate the Effect of Itraconazole and Rifampin on the Pharmacokinetics of Talazoparib in Patients With Advanced Solid Tumors

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