Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Talazoparib in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03070548
Recruitment Status : Completed
First Posted : March 3, 2017
Results First Posted : December 17, 2018
Last Update Posted : December 17, 2018
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This study will evaluate the mass balance of talazoparib after a single dose of talazoparib.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: Talazoparib Phase 1

Detailed Description:
Patients participating in this study with no clinically significant toxicities may be eligible to continue treatment on a separate extension protocol after discussion with the Principal Investigator and obtaining Sponsor permission..

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-label Study Of 14c-labeled Talazoparib In Patients With Advanced Solid Tumors
Actual Study Start Date : September 2016
Actual Primary Completion Date : June 2017
Actual Study Completion Date : June 2017

Arm Intervention/treatment
Experimental: ADME
1 mg talazoparib containing100 μCi of 14C-radiolabeled talazoparib
Drug: Talazoparib
1 mg of talazoparib containing100 μCi of 14C-radiolabeled talazoparib
Other Names:
  • MDV3800
  • BMN673




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of Talazoparib [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
  2. Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
  3. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Talazoparib [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf).

  4. Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration.

  5. Terminal Elimination Half-Life (t1/2) of Talazoparib [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half.

  6. Apparent Total Plasma Clearance (CL/F) of Talazoparib [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

  7. Apparent Volume of Distribution (Vd/F) of Talazoparib [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of the drug.

  8. Maximum Observed Plasma Concentration (Cmax) of 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  9. Time to Attain Maximum Observed Plasma Concentration (Tmax) of 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  10. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  11. Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  12. Terminal Elimination Half-Life (t1/2) of 14C- Radioactivity in Plasma [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    Terminal elimination half-life was defined as the time measured for the plasma radioactivity concentration to decrease by one half. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  13. Apparent Total Plasma Clearance (CL/F) of 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  14. Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Plasma [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  15. Maximum Observed Whole Blood Concentration (Cmax) of 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  16. Time to Attain Maximum Observed Whole Blood Concentration (Tmax) of 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  17. Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  18. Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  19. Apparent Total Whole Blood Clearance (CL/F) of 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  20. Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Whole Blood [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of the drug. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  21. Amount of Talazoparib Excreted in Urine During Each Collection Interval (Ae t1-t2) [ Time Frame: Pre-dose, 0 to 8 hours (hrs), 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose ]
    Ae t1-t2 was defined as the amount of talazoparib excreted into urine during each collection interval (t1-t2).

  22. Percentage of Dose of Talazoparib Excreted During Each Collection Interval (Aet1-t2%) of Talazoparib [ Time Frame: Pre-dose, 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose ]
    Aet1-t2% was the percentage of Aet1-t2, where Aet1-t2 was defined as the amount of talazoparib excreted into urine during each collection interval (t1-t2).

  23. Renal Clearance (CLr) of Talazoparib [ Time Frame: Pre-dose, 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose ]
    Renal clearance was calculated as cumulative amount of drug excreted in urine divided by AUC(0-last) (area under the plasma concentration-time curve from zero to the time of the last measurable concentration).

  24. The Recovery of 14C-Radioactivity as a Percentage of the Administered Dose [ Time Frame: From 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs and then after every 24 hrs until up to 504 hrs post-dose ]
    Recovery of 14C-radioactivity in urine and feces was calculated in terms of percentage of administered dose after administration of a single 1 mg dose of oral solution (containing 100 micro-curie 14C-labeled talazoparib).


Secondary Outcome Measures :
  1. Ratio of Maximum Observed Plasma Concentration to Maximum Observed Whole Blood Concentration for 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    100 micro-curie of 14C radiolabeled talazoparib was present in 1 mg of talazoparib.

  2. Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity to Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity for 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  3. Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration to Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable for 14C- Radioactivity [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose ]
    AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

  4. Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: Day 1 to 14 days after last day of mass balance phase and at least 30 days after Day1/before initiation of new cytotoxic chemotherapy, new investigational treatment/first day of extension protocol, whichever occurs first(up to maximum duration of 8 weeks) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug through 14 days after the last day of mass balance phase and at least 30 days after Day 1 or before initiation of new cytotoxic chemotherapy, new investigational treatment, or the first day of extension protocol, whichever occurs first (up to maximum duration of 8 weeks from screening to follow-up for each participant) or before initiation of new cytotoxic chemotherapy, new investigational treatment, or the first day of extension protocol, whichever occurs first, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both non-serious (AEs) and serious adverse events (SAEs).

  5. Number of Participants With Clinically Significant Vital Signs Parameters [ Time Frame: Baseline up to Day 22 ]
    Vital Signs included heart rate, respiratory rate, body temperature, systolic blood pressure and diastolic blood pressure. clinical significance of vital signs was determined at the investigator's discretion.

  6. Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities [ Time Frame: Baseline up to Day 22 ]
    Criteria for clinically significant ECG abnormalities : Heart Rate; increase from baseline greater than (>)25 %and to a value >100, decrease from baseline >25% and to a value < 50; PR Interval: increase from baseline >25% and to a value >200; QRS Duration: increase from baseline >25% and to a value >100; QT interval using Fridericia's correction (QTcF): ranges >450 msec, >480 msec, >500 msec, Increase from baseline >30 msec and >60 msec; QT Interval: ranges >450 msec, >480 msec, >500 msec, Increase from baseline >30 msec and >60 msec.

  7. Number of Participants With Clinically Significant Laboratory Abnormalities [ Time Frame: Baseline up to Day 22 ]
    Haematological, biochemistry and urinalysis parameters. Biochemistry parameters:alkaline phosphatase 30-120units per liter(U/L), creatinine 53-110micromole/L(micromol/L), gamma glutamyl transferase 7-50U/L, glucose 3.3-5.5millimoles/L(mmol/L), lactate dehydrogenase 200-460U/L, triglycerides 0.4-1.7mmol/L, cholesterol 2.6-5.2mmol/L, phosphate 0.8-1.45mmol/L, sodium 135-146mmol/L, urea 2.8-7.2mmol/L, chloride 95-109mmol/L, creatine kinase 24-170U/L, aspartate aminotransferase 4-46U/L, potassium 3.5-5.5mmol/L. Haematology parameters:haemoglobin 120-155 gram/L(g/L), erythrocytes 4-5.2 10^12/L, haematocrit 0.35-0.45, prothrombin time 13.7-15.6 second(sec), lymphocytes 1-3.7 10^9/L, platelets 150-400 10^9/L, prothrombin intl. normalized ratio 0.89-1.1, activated partial thromboplastin time 25-43 sec, basophils 0-0.09 10^9/L, neutrophils 1.5-7 10^9/L, and leukocytes 4-10 10^9/L. Urinalysis parameters:urinalysis specific gravity 1.012-1.03, urinalysis pH 4.8-7.8.

  8. Number of Participants With Change From Baseline in Physical Examination Findings [ Time Frame: Baseline up to Day 22 ]
    Physical examination included examination of abdomen, cardiovascular, eyes, ears, nose, throat, general appearance, head, neck, thyroid, lymph nodes, musculoskeletal, neurological, skin/subcutaneous tissue and thorax/lungs.

  9. Amount of Any Significant Metabolites of Talazoparib in Urine and Feces [ Time Frame: From 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs and then after every 24 hrs until up to 504 hrs post-dose ]
    M4 (M481/1, cysteine conjugate of mono-desfluoro-talazoparib) metabolite was found in urine. MDV10595 (M1, dehydrogenated talazoparib (PF-07052386), M556/1 (glucuronide conjugate of talazoparib), and M2 (M396/1, mono-oxidative talazoparib) metabolites were calculated together and were also found in urine. Three metabolites named as: MDV10595 (M1)/M556/1 and M2 (M396/1) which were calculated together were detected in feces. Amount of metabolite in this outcome measure was measured in terms of percentage of dose of talazoparib.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. At least 18 years of age 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. Eastern Co-Operative Oncology Group (ECOG) performance status ≤ 2 at screening and Day -1.
  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 of childbearing potential using a highly effective form of contraception, and female subjects should not donate eggs from the time point of 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 from 21 days before the first dose of study drug through 105 days after the last dose of study drug, and males should not donate sperm from the time point of study drug administration until at least 105 days thereafter.
  8. Female patients 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 weeks or five half-live 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. Patients 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 solution components.
  11. Use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BRCP within 7 days or 5 half-lives, whichever is longer, before Day 1.
  12. 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]).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03070548


Locations
Layout table for location information
Hungary
PRA Magyarorszag Kft, Fazis I-es Klinikai Farmakologiai Vizsgalohely
Budapest, Hungary, 1077
Sponsors and Collaborators
Pfizer
Medivation, Inc.
Investigators
Layout table for investigator information
Study Director: Pfizer Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] October 7, 2016
Statistical Analysis Plan  [PDF] July 16, 2017

Additional Information:
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03070548    
Other Study ID Numbers: MDV3800-03
C3441003 ( Other Identifier: Alias Study Number )
2016-001394-33 ( EudraCT Number )
First Posted: March 3, 2017    Key Record Dates
Results First Posted: December 17, 2018
Last Update Posted: December 17, 2018
Last Verified: May 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents