Phase 1
Completed N=36
A Study to Evaluate the Effect of Itraconazole and Rifampin on the Pharmacokinetics of Talazoparib in Patients With Advanced Solid Tumors
Source: ClinicalTrials.gov NCT03077607 ↗Enrolled (actual)
36
Serious AEs
6.1%
Results posted
Mar 2019
Primary outcomePrimary: Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole — 2092.00; 2936.82 Picogram per milliliter (pg/mL)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole |
2092.00; 2936.82 | — |
| 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 |
98532.30; 145944.59 | — |
| PRIMARY 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; 151919.63 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Rifampin |
6007.01; 8336.83 | — |
| 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 |
196631.34; 196100.69 | — |
| 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 |
209521.62; 194307.67 | — |
| SECONDARY Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Itraconazole |
1.00; 1.02 | — |
| SECONDARY Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Itraconazole |
101.26; 118.47 | — |
| SECONDARY Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Itraconazole |
4.55; 3.29 | — |
| SECONDARY Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Itraconazole |
644.81; 552.01 | — |
| SECONDARY Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Rifampin |
1.00; 1.00 | — |
| SECONDARY Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Rifampin |
92.05; 80.61 | — |
| SECONDARY Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Rifampin |
623.89; 588.14 | — |
| SECONDARY Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Rifampin |
4.77; 5.15 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
12; 3; 5; 6; 9; 5 | — |
| SECONDARY Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters |
3; 0; 1; 2; 1; 1 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormalities in Vital Signs |
0; 0; 1; 0; 0; 1 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Physical Examination Findings |
0; 0; 1; 1; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- 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.
- 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.
- ECOG performance status ≤ 2 at screening and at time of enrollment.
- Expected life expectancy of ≥ 3 months.
- Able to swallow the study drug and comply with study requirements.
- 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.
- 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.
- Female subjects must not be breastfeeding at screening and during the study participation until 45 days after the last dose of the study drug.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Exclusion Criteria
- 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
- Major surgery within 8 weeks before screening.
- Serious accompanying disorder or impaired organ function.
- Symptomatic or impending spinal cord compression or cauda equina syndrome.
- Non-healing wound, ulcer, or bone fracture, not including a pathological bone fracture caused by a pre-existent pathological bone lesion.
- Known myelodysplastic syndrome.
- Subjects with the following serologies should be excluded: HBsAg+ or anti-HBc+;HCV+; HIV+.
- Serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
- Gastrointestinal disorder affecting absorption.
- Known hypersensitivity to any of the talazoparib capsule components.
- 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].
Data sourced from ClinicalTrials.gov (NCT03077607). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.