A Pharmacokinetics and Tolerability Study of Fedratinib in Subjects With Moderate and Severe Hepatic Impairment

NCT03983161 | Completed Phase 1 FDA Drug

• 2 other identifiers: FEDR-CP-001U1111-1233-7820
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1, multicenter, nonrandomized, open-label, single oral dose study to assess the PK of fedratinib in subjects with moderate and severe hepatic impairment, and in matched subjects with normal hepatic function. Degrees of hepatic impairment will be determined during screening by the subject's score according to Pugh's Modification of Child's Classification of Severity of Liver Disease.

Conditions

Healthy Volunteers; Hepatic Impairment

Keywords

Healthy Subjects; Fedratinib; Hepatic impairment; Pharmacokinetics

Outcome Measures

Primary Outcomes (7)

• Fedratinib Pharmacokinetic (PK): AUC0-t

  Estimation of AUC from time zero to the last measured time point

  Up to approximately 8 days.

• Fedratinib Pharmacokinetic (PK): AUC0-∞

  Estimation of AUC from time zero extrapolated to infinity

  Up to approximately 8 days.

• Fedratinib Pharmacokinetic (PK): Cmax

  Estimation of maximum observed plasma concentration

  Up to approximately 8 days.

• Fedratinib Pharmacokinetic (PK): Tmax

  Estimation of time to reach Cmax

  Up to approximately 8 days.

• Fedratinib Pharmacokinetic (PK): t1/2

  Estimation of terminal elimination half-life

  Up to approximately 8 days.

• Fedratinib Pharmacokinetic (PK): CL/F

  Estimation of apparent total plasma clearance when dosed orally

  Up to approximately 8 days.

• Fedratinib Pharmacokinetic (PK): Vz/F

  Estimation of apparent volume of distribution when dosed orally

  Up to approximately 8 days.

Secondary Outcomes (1)

• Adverse Events (AEs)

  From enrollment until at least 30 days after completion of study treatment

Study Arms (4)

Fedratinib in moderate hepatic impairment subjects

EXPERIMENTAL

A single oral dose of 300 mg of fedratinib will be given to subjects with moderate hepatic impairment

Drug: Fedratinib

Fedratinib in severe hepatic impairment subjects

EXPERIMENTAL

A single dose of 200 mg of fedratinib will be given to subjects with severe hepatic impairment

Drug: Fedratinib

Fedratinib in healthy vs moderate hepatic impairment subjects

EXPERIMENTAL

A single oral dose of 300 mg of fedratinib will be given to healthy subjects with normal hepatic function.

Drug: Fedratinib

Fedratinib in healthy vs severe hepatic impairment subjects

EXPERIMENTAL

A single oral dose of 200 mg of fedratinib will be given to healthy subjects with normal hepatic function.

Drug: Fedratinib

Interventions

Fedratinib DRUG

Fedratinib

Fedratinib in healthy vs moderate hepatic impairment subjects; Fedratinib in healthy vs severe hepatic impairment subjects; Fedratinib in moderate hepatic impairment subjects; Fedratinib in severe hepatic impairment subjects

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements, including the restrictions
• Subject is male, or non-pregnant and non-nursing female ≥ 18 and ≤ 75 years of age at the time of signing the Informed Consent Form (ICF).
• Subject has body mass index (BMI) ≥ 18 and ≤ 40 kg/m2 at screening.
• Female subjects NOT of childbearing potential must:
• a. Have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper documentation required) at least 6 months before Screening, or postmenopausal (defined as 24 consecutive months without menses before Screening, with a follicle-stimulating hormone \[FSH\] level in the post-menopausal range according to the laboratory used at Screening); FSH to be performed at the discretion of the Investigator in consultation with the Sponsor's Medical Monitor.
• A female of childbearing potential (FCBP) must:
• Have a negative pregnancy test as verified by the Investigator at Screening and Baseline (prior to starting study treatment). She must agree to ongoing pregnancy testing during the course of the study, as applicable, and after the end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
• Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis, as applicable, and source documented) or agree to use, and be able to comply with, any one of the following highly effective contraception methods without interruption, beginning at least 14 days prior to dosing, during the study treatment, and for at least 30 days after the last dose of IP.
• Hormonal contraception (eg, birth control pills, intravaginal ring, transdermal patch, injection, implant); intrauterine device (IUD); tubal ligation; or a partner with a vasectomy. The chosen form of birth control must be effective by the time the subject receives the first dose of IP.
• Male subjects must:
• a. Practice true abstinence (which must be reviewed monthly, as applicable, and source documented) or agree to use a barrier method of birth control (condoms not made from natural \[animal\] membrane \[latex condoms are recommended\]) during sexual contact with a pregnant female or FCBP while receiving study treatment, and for at least 30 days after the last dose of IP, even if he has undergone a successful vasectomy.
• Subject has clinical laboratory safety test results that are within normal limits or acceptable to the Investigator.
• Subject is afebrile (febrile is defined as ≥ 38°C or 100.3°F), with supine systolic blood pressure (BP) ≥ 90 and ≤ 160 mm Hg, supine diastolic BP ≥ 50 and ≤ 100 mm Hg, and pulse rate ≥ 40 and ≤ 100 beats per minute at Screening.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject has prior history of Wernicke's encephalopathy (WE).
• Subject has thiamine deficiency, defined as thiamine levels in whole blood below normal range according to institutional standard and not demonstrated to be corrected prior to enrollment into the study.
• Subject has any significant and relevant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study at the Investigator's discretion.
• Subject has any condition that places the subject at an unacceptable risk if he or she were to participate in the study.
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject is pregnant or breastfeeding.
• Subject was exposed to an investigational drug (new chemical entity) within 30 days preceding the first dose administration, or 5 half-lives of that investigational drug, if known (whichever was longer).
• Subject has used moderate or strong CYP3A4 and/or CYP2C19 inducers and/or inhibitors (including St. John's wort) within 14 days or 5 half-lives, whichever is longer, prior to the first dose administration. The Indiana University "Cytochrome P450 Drug Interaction Table" should be utilized to determine inhibitors and/or inducers of CYP3A4 (http://medicine.iupui.edu/clinpharm/ddis/table.aspx).
• Subject has any surgical or medical condition(s) possibly affecting drug absorption, distribution, metabolism, and excretion, eg, bariatric procedure. Subjects with appendectomy and cholecystectomy may be included.
• Subject donated blood or plasma within 2 weeks before dose administration to a blood bank or blood donation center.
• Subject has a history of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual) within 2 years before dose administration, or positive drug screening test reflecting consumption of illicit drugs.
• a. If positive drug screen in a subject with hepatic impairment is due to prescription drug use, the specific drug and dosing regimen of the prescription drug must be reviewed with the Sponsor's Medical Monitor to ensure lack of interference with the PK assessments of this study, according to the protocol. The decision and its rationale will be documented in the Trial Master File.
• Subject has a history of alcohol abuse (as defined by the current version of the Diagnostic and Statistical Manual) within 1 year before dose administration, or a positive alcohol screen.
• Subject has had a positive result to the test for human immunodeficiency virus (HIV) antibodies at Screening.

Sponsors & Collaborators

• Celgene: lead
• Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation: collaborator

Study Sites (3)

University Of Miami Miller School Of Medicine

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center OCRC

Orlando, Florida, 32809, United States

Location

Volunteer Research Group and New Orleans Center for Clinical Research - Knoxville

Knoxville, Tennessee, 37920, United States

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

MeSH Terms

Interventions

fedratinib

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 10, 2019
• First Posted: June 12, 2019
• Study Start: September 4, 2019
• Primary Completion: January 5, 2023
• Study Completion: January 5, 2023
• Last Updated: March 17, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (3)