An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800)

NCT02997176 | Completed Phase 1 Results

• 2 other identifiers: MDV3800-02C3441002
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 11

Brief Summary

This is a trial to investigate the pharmacokinetics (PK) and the safety of talazoparib in patients with advanced solid tumors and impaired hepatic function.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22

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

  Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22

• Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22

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

  Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22

• Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22

  AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu\*AUC0-24. fu= Fraction of Unbound (fu) Plasma.

  Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22

• Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22

  Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu\*Cmax.

  Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22

Secondary Outcomes (24)

• Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1

  Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1

• Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1

  Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1

  Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1

• Fraction of Unbound (fu) Plasma Talazoparib on Day 1

  Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1

• Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1

  Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1

Other Outcomes (4)

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

  Baseline up to 30 days after last dose of study drug (up to 52 days)

• Number of Participants With TEAEs Leading to Study Drug Discontinuation

  Baseline up to 30 days after last dose of study drug (up to 52 days)

• Number of Participants With TEAEs Resulting in Death

  Baseline up to 30 days after last dose of study drug (up to 52 days)

Study Arms (4)

Group A (control, normal hepatic function)

EXPERIMENTAL

Drug: Talazoparib

Group B (mild hepatic dysfunction)

EXPERIMENTAL

Drug: Talazoparib

Group C (moderate hepatic dysfunction)

EXPERIMENTAL

Drug: Talazoparib

Group D (severe hepatic dysfunction)

EXPERIMENTAL

Drug: Talazoparib

Interventions

Talazoparib DRUG

Daily oral doses of talazoparib 0.5 mg

Also known as: MDV3800, BMN673

Group A (control, normal hepatic function); Group B (mild hepatic dysfunction); Group C (moderate hepatic dysfunction); Group D (severe hepatic dysfunction)

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).
• Female or male at least 18 years of age.
• Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the Investigator
• Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.
• Expected life expectancy of ≥ 3 months.
• Able to swallow the study drug (no contraindication to oral agents).
• Hepatic function at screening and enrollment as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria.
• 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 form of contraception from the time of the first dose of study drug through 7 months 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 4 months after last dose of study drug.
• Female patients must not be breastfeeding at screening nor during the study participation until 7 months after the last dose of the 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 whichever is longer with any type of systemic anticancer-therapy or any investigational drug
• 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 needing treatment
• Symptomatic or impending spinal cord compression or cauda equine 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 (11)

UCLA Hematology/Oncology - Alhambra

Alhambra, California, 91801, United States

Location

CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

St. Joseph Heritage Healthcare

Fullerton, California, 92835, United States

Location

St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare

Fullerton, California, 92835, United States

Location

UCLA Hematology/Oncology

Los Angeles, California, 90095, United States

Location

UCLA Hematology/Oncology - Porter Ranch

Porter Ranch, California, 91326, United States

Location

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

UCLA Torrance Oncology

Torrance, California, 90505, United States

Location

UCLA Hematology/Oncology - Santa Clarita

Valencia, California, 91355, United States

Location

Orlando Health, Inc.

Orlando, Florida, 32806, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

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 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: September 30, 2016
• Primary Completion: February 12, 2020
• Study Completion: February 12, 2020
• Last Updated: February 25, 2021
• Results First Posted: February 25, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)