An Open-Label Pharmacokinetics and Safety Study of Talazoparib

NCT02997163 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: MDV3800-01C34410012016-002536-33
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 10

Brief Summary

This trial will investigate the pharmacokinetics (PK) and safety of talazoparib in patients with advanced solid tumors and impaired renal function.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib

  AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose.

  Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

• Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib

  Cmax was defined as the maximum observed plasma concentration of talazoparib.

  Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

• Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib

  AUC0-24u for unbound talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose.

  Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

• Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib

  Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib.

  Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

Secondary Outcomes (27)

• Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib

  Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

• Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib

  Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

• Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib

  Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

• Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib

  Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

• Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib

  Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

Study Arms (4)

Group A (control, normal renal function)

EXPERIMENTAL

Drug: Talazoparib

Group B (mild renal impairment)

EXPERIMENTAL

Drug: Talazoparib

Group C (moderate renal impairment)

EXPERIMENTAL

Drug: Talazoparib

Group D (severe renal impairment)

EXPERIMENTAL

Drug: Talazoparib

Interventions

Talazoparib DRUG

Daily oral doses of talazoparib 0.5 mg

Also known as: MDV3800, BMN673

Group A (control, normal renal function); Group B (mild renal impairment); Group C (moderate renal impairment); Group D (severe renal impairment)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent form (by the patient or a legally acceptable representative as per the local regulations) obtained prior to initiation of any study-specific procedure and treatment.
• Female or male of at least 18 years of age.
• Histologically or cytologically confirmed advanced solid tumor with no available standard approved treatment options in the opinion of the Investigator
• Eastern Cooperative Oncology Group (ECOG) Performance status (PS) ≤ 2.
• Expected life expectancy of ≥ 3 months.
• Able to swallow the study drug (no contra indication to oral agents).
• Renal function at screening and enrollment as defined by the Modification of Diet in Renal Disease (MDRD) equation.
• Patient has had no clinically significant change in renal status within 3 months prior to screening, according to Investigator's review of clinical patient records.
• Patient is not currently on hemodialysis and/or peritoneal dialysis for management of chronic kidney disease or acute failure/conditions.
• Patient has no unstable renal function, defined as a change in estimated glomerular filtration rate (eGFR) (calculated with the MDRD equation) of \> 25% for patients with mild and moderate renal impaired or as a change in eGFR \> 30% for patients with severe renal impaired, from screening to enrollment.
• Adequate other organ function at screening and enrollment.
• Female patients of childbearing potential must have a negative serum pregnancy test at screening, and must agree to use a highly effective birth control method from the time of the first dose of study drug through 45 days after the last dose of study drug.
• Male patients must agree to use a condom when having sex with a pregnant woman or with a non-pregnant female partner of childbearing potential, from 21 days before the first dose of study drug through 105 days after last dose of study drug.
• Female patients must not be breastfeeding at screening nor during the study participation until 45 days after the last dose of study drug.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

You may not qualify if:

• Treatment within 14 days or five half lives prior to enrollment with any type of systemic anticancer-therapy or any investigational drug, whichever is longer.
• Have not recovered (recovery is defined as CTCAE grade ≤ 1) from the acute toxicities of previous anticancer standard or investigational therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
• Major surgery within 28 days prior to enrollment.
• Serious accompanying cardiac disorder.
• Active known or suspected brain metastasis or active leptomeningeal disease undergoing or requiring treatment.
• Symptomatic or impending spinal cord compression or cauda equina syndrome.
• Has undergone a liver transplant, kidney transplant or nephrectomy.
• Prior allergic reaction or severe intolerance (meeting the criteria for a serious adverse event, a grade 3 or 4 AE, or permanent treatment discontinuation) to a poly ADP ribose polymerase (PARP) inhibitor.
• Known myelodysplastic syndrome.
• Seropositive for human immunodeficiency virus (HIV).
• Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
• Gastrointestinal disorder affecting absorption.
• Known or suspected hypersensitivity to any of the talazoparib capsule components.
• Any condition or reason that interferes with ability to participate in the study, tolerate treatment or assessments associated with the protocol, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator or Medical Monitor.

Sponsors & Collaborators

• Pfizer: lead
• Medivation, Inc.: collaborator

Study Sites (10)

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, 46804, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, 46845, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Karmanos Cancer Institute Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

Location

Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08901, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (1)

• Durairaj C, Chakrabarti J, Ferrario C, Hirte HW, Babu S, Piha-Paul SA, Plotka A, Hoffman J, Shi H, Wang DD. The Effect of Renal Impairment on the Pharmacokinetics and Safety of Talazoparib in Patients with Advanced Solid Tumors. Clin Pharmacokinet. 2021 Jul;60(7):921-930. doi: 10.1007/s40262-020-00983-y. Epub 2021 Mar 9.

  PMID: 33686631 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

talazoparib

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2016
• First Posted: December 19, 2016
• Study Start: February 21, 2017
• Primary Completion: January 30, 2019
• Study Completion: January 30, 2019
• Last Updated: January 5, 2021
• Results First Posted: February 20, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); US (7)