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.
Condition or disease | Intervention/treatment | Phase |
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Healthy Volunteers Hepatic Impairment | Drug: Fedratinib | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 32 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1 Open-label, Single-dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Fedratinib in Subjects With Moderate and Severe Hepatic Impairment Compared With Healthy Subjects |
Actual Study Start Date : | July 15, 2019 |
Estimated Primary Completion Date : | December 31, 2021 |
Estimated Study Completion Date : | December 31, 2021 |
Arm | Intervention/treatment |
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Experimental: Fedratinib in moderate hepatic impairment subjects
A single oral dose of 300 mg of fedratinib will be given to subjects with moderate hepatic impairment
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Drug: Fedratinib
Fedratinib
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Experimental: Fedratinib in severe hepatic impairment subjects
A single dose of 200 mg of fedratinib will be given to subjects with severe hepatic impairment
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Drug: Fedratinib
Fedratinib
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Experimental: Fedratinib in healthy vs moderate hepatic impairment subjects
A single oral dose of 300 mg of fedratinib will be given to healthy subjects with normal hepatic function.
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Drug: Fedratinib
Fedratinib
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Experimental: Fedratinib in healthy vs severe hepatic impairment subjects
A single oral dose of 200 mg of fedratinib will be given to healthy subjects with normal hepatic function.
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Drug: Fedratinib
Fedratinib
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Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Inclusion Criteria for all subjects (Groups 1 through 4)
Subjects must satisfy the following criteria to be enrolled in the study:
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:
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.
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 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.
Inclusion Criteria for Subjects with Moderate or Severe Hepatic Impairment (Groups 1 and 3)
Each subject with moderate or severe hepatic impairment must also meet all the criteria listed below for entry:
Subject has moderate (Group 1) or severe (Group 3) hepatic impairment as defined by Child-Pugh Score.
If biopsy or laparoscopy is not performed prior to Screening, subjects can be included only if they have chronic liver disease and objective evidence of portal hypertension (ascites diagnosis by imaging or varices), or current medication for consequences of portal hypertension.
Subjects should be enrolled into the group corresponding to the Child-Pugh classification score that most accurately reflects the most severe hepatic disease classification within the past 6 months (based on past medical history or physical examination observation).
*Note: If a Child-Pugh score was previously calculated and documented in the last 6 months, and it is more severe than the one calculated at Screening, then that previous value will be used for study entry purposes. If the Screening Child-Pugh score is more severe, then it will be used. If no score was calculated in the 6 months prior to Screening, then the score obtained at Screening will be used. Adequate documentation should be provided to substantiate the Child-Pugh score assigned to each subject.
Subject must have estimated creatinine clearance ≥ 60 mL/min at Screening as calculated by the Cockcroft-Gault formula.
Inclusion Criteria for a Matched Healthy Subjects (Groups 2 and 4) Each matched healthy subject must meet all the criteria listed below for entry:
Subject has a normal or clinically acceptable 12-lead ECG at Screening. In addition:
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
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 incipient/planned liver transplantation within 6 months of Screening or has received a liver transplant.
Exclusion Criteria for a Matched Healthy Subject (Groups 2 and 4) Each matched healthy subject will be excluded from entry if any of the criteria listed below are met:
Subject has used any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 30 days or 5 drug half-lives (whichever is longer) prior to the first dose administration of fedratinib.
a. A subject who has used (or will have used) a prescribed medication less than 30 days prior to (but at least 5 half-lives prior to) fedratinib dosing may be admitted into the study if such usage is not expected by the Investigator to have persistent PK effects at the time of fedratinib dosing. Such effects may include, but are not limited to, cytochrome induction or covalent cytochrome inhibition. These cases must be approved by Sponsor's Medical Monitor. The decision and its rationale will be documented in the Trial Master File.
Subject has used any nonprescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days or 5 drug half-lives (whichever is longer) prior to the first dose administration of fedratinib.
a. A subject who has used (or will have used) a nonprescribed medication less than 14 days prior to (but at least 5 half-lives prior to) fedratinib dosing may be admitted into the study if such usage is not expected by the Investigator to have persistent PK effects at the time of fedratinib dosing. Such effects may include, but are not limited to, cytochrome induction or covalent cytochrome inhibition. These cases must be approved by Sponsor's Medical Monitor. The decision and its rationale will be documented in the Trial Master File.
Contact: Associate Director Clinical Trial Disclosure | 1-888-260-1599 | clinicaltrialdisclosure@celgene.com |
United States, Florida | |
University of Miami Miller School of Medicine | Recruiting |
Miami, Florida, United States, 33136 | |
Orlando Clinical Research Center OCRC | Recruiting |
Orlando, Florida, United States, 32809 | |
United States, Tennessee | |
Volunteer Research Group and New Orleans Center for Clinical Research - Knoxville | Recruiting |
Knoxville, Tennessee, United States, 37920 |
Study Director: | Leon Carayannopoulos, MD | Celgene Corporation |
Tracking Information | |||||||||||||||||||||
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First Submitted Date ICMJE | June 10, 2019 | ||||||||||||||||||||
First Posted Date ICMJE | June 12, 2019 | ||||||||||||||||||||
Last Update Posted Date | December 3, 2020 | ||||||||||||||||||||
Actual Study Start Date ICMJE | July 15, 2019 | ||||||||||||||||||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||||||||||||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||||||||||||||
Change History | |||||||||||||||||||||
Current Secondary Outcome Measures ICMJE |
Adverse Events (AEs) [ Time Frame: From enrollment until at least 30 days after completion of study treatment ] Number of participants with adverse event
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||||||||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||||||||
Descriptive Information | |||||||||||||||||||||
Brief Title ICMJE | A Pharmacokinetics and Tolerability Study of Fedratinib in Subjects With Moderate and Severe Hepatic Impairment | ||||||||||||||||||||
Official Title ICMJE | A Phase 1 Open-label, Single-dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Fedratinib in Subjects With Moderate and Severe Hepatic Impairment Compared With Healthy Subjects | ||||||||||||||||||||
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. |
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Detailed Description | Not Provided | ||||||||||||||||||||
Study Type ICMJE | Interventional | ||||||||||||||||||||
Study Phase ICMJE | Phase 1 | ||||||||||||||||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE | Drug: Fedratinib
Fedratinib
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||||||||||
Recruitment Status ICMJE | Recruiting | ||||||||||||||||||||
Estimated Enrollment ICMJE |
32 | ||||||||||||||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||||||||||||||
Estimated Study Completion Date ICMJE | December 31, 2021 | ||||||||||||||||||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||||||||||||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria: Inclusion Criteria for all subjects (Groups 1 through 4) Subjects must satisfy the following criteria to be enrolled in the study:
Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 75 Years (Adult, Older Adult) | ||||||||||||||||||||
Accepts Healthy Volunteers ICMJE | Yes | ||||||||||||||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||||||||||||||||
Removed Location Countries | |||||||||||||||||||||
Administrative Information | |||||||||||||||||||||
NCT Number ICMJE | NCT03983161 | ||||||||||||||||||||
Other Study ID Numbers ICMJE | FEDR-CP-001 U1111-1233-7820 ( Other Identifier: WHO ) |
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Has Data Monitoring Committee | No | ||||||||||||||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Celgene | ||||||||||||||||||||
Study Sponsor ICMJE | Celgene | ||||||||||||||||||||
Collaborators ICMJE | Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation | ||||||||||||||||||||
Investigators ICMJE |
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PRS Account | Celgene | ||||||||||||||||||||
Verification Date | December 2020 | ||||||||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |