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Healthy VolunteersPhase 1NCT04702464

A Study to Evaluate the Effect of a Dual CYP2C19 and CYP3A4 Inhibitor, Fluconazole, on the Pharmacokinetics of Fedratinib in Healthy Adult Subjects

A Phase 1 study testing Fedratinib and Fluconazole in people with Healthy Volunteers, run by Celgene at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is designed to test the effect of fluconazole (a dual CYP2C19 and CYP3A4 inhibitor) on the Pharmacokinetics (PK) of fedratinib. Knowledge of these effects can be used to determine if dose adjustments should be considered when fedratinib is coadministered with drugs that are dual CYP2C19 and CYP3A4… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Volunteers
What is being tested?
Fedratinib and Fluconazole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
12 Jan 2021to 13 May 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Subjects must satisfy the following criteria to be enrolled in the study:
  • Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
  • Subject must be willing and able to communicate with the Investigator and adhere to the study visit schedule and other protocol requirements.
  • Subject is male or female of any race ≥ 18 to ≤ 65 years of age at the time of signing the ICF.
  • Female subjects NOT of childbearing potential must:
  • 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).
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  • Females of childbearing potential (FCBP1) 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 and after end of study treatment. This applies even if the subject practices true abstinence2 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 starting investigational product (IP), during the study treatment, and for at least 30 days after the last dose of IP.
  • Intrauterine device (IUD; non-hormonal only); 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:
  • Practice true abstinence from heterosexual contact (which must be reviewed on a monthly basis, 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.
  • Must have a body mass index (BMI) ≥ 18 and ≤ 33 kg/m2 at screening.
  • Must be healthy, as determined by the Investigator on the basis of medical history, physical examination (PE), clinical laboratory test results, vital signs, and 12-lead electrocardiogram (ECG) at screening and check-in (Day -1), as applicable:
  • Aspartate aminotransferase (AST), ALT, and total bilirubin must be at or below the upper limit of the reference range on or before check-in (Day -1). Other clinical laboratory results must be either within normal range or deemed not clinically significant by the Investigator. Any out of range lab tests may be repeated up to 1 time during Screening and up to 1 time at check-in per Investigator discretion to confirm eligibility.
  • Must be afebrile (febrile is defined as ≥ 38°C or 100.3°F).
  • Supine systolic blood pressure (BP) must be in the range of 90 to 150 mmHg (inclusive), supine diastolic BP must be in the range of 50 to 90 mmHg (inclusive), and pulse rate must be in the range of 45 to 90 bpm (inclusive) at Screening. Any out of range vital sign measurements may be repeated up to 1 time during Screening and up to 1 time at check-in per Investigator discretion to confirm eligibility.
  • Subject has a normal or clinically acceptable 12-lead ECG at screening; male subjects must have a corrected QT interval using Fridericia's formula (QTcF) value ≤ 430 msec and females must have a QTcF value ≤ 450 msec. An ECG may be repeated up to 2 times, and the average of the QTcF values will be used to determine subject eligibility.

Who cannot join

  • The presence of any of the following will exclude a subject from enrollment:
  • History (within 3 years prior to Screening) of any clinically significant neurological, GI, hepatic, renal, respiratory, cardiovascular, metabolic, endocrine, hematological, dermatological, psychological, or other major disorders as determined by the Investigator.
  • Any condition, including the presence of laboratory abnormalities, that places the subject at unacceptable risk if he or she were to participate in the study or confounds the ability to interpret data from the study (congenital nonhemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is not acceptable).
  • Subject has prior history of Wernicke's Encephalopathy (WE).
  • Subject has signs or symptoms of WE (eg, ataxia, ocular paralysis, or cerebellar signs) without documented exclusion of WE by thiamine level and brain magnetic resonance imaging (MRI).
  • Subject has thiamine deficiency, defined as thiamine levels in whole blood below normal range according to institutional standard.
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  • Use of any prescribed systemic or topical medication, including vaccines, within 30 days of the first dose administration (with the exception of ondansetron administered for purposes of this study).
  • Use of any nonprescribed systemic or topical medication (including vitamin/mineral supplements and herbal medicines) within 14 days of the first dose administration (with the exception of acetaminophen up to 2 grams/day for no more than 3 consecutive days to treat minor illness or headache [per Investigator judgment]).
  • Use of any metabolic enzyme or relevant transporter inhibitors or inducers that would affect the relevant drugs within 30 days of the first dose administration unless determined by the Investigator that there will be no impact on the study integrity or subject safety.
  • The Indiana University "P450 Drug Interaction Table" should be used to determine inhibitors and/or inducers of metabolic enzymes (http://medicine.iupui.edu/clinpharm/ddis/table/aspx). The Sponsor should be contacted for questions about potential drug-drug interactions and exclusions/prohibitions when necessary.
  • Exposure 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 is longer).
  • Presence of any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism, and excretion (eg, bariatric procedure, cholecystectomy). Appendectomy is acceptable.
  • Donated blood or plasma within 8 weeks before the first dose administration.
  • History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual [DSM]) within 2 years before dosing or positive drug screening test reflecting consumption of illicit drugs.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • PPD Phase 1 Clinic

    Austin, Texas, 78744

Other trials in United States

About this study

Official title: A Phase 1, Open-label Study to Evaluate the Effect of a Dual CYP2C19 and CYP3A4 Inhibitor, Fluconazole, on the Pharmacokinetics of Fedratinib in Healthy Adult Subjects

This study is designed to test the effect of fluconazole (a dual CYP2C19 and CYP3A4 inhibitor) on the Pharmacokinetics (PK) of fedratinib. Knowledge of these effects can be used to determine if dose adjustments should be considered when fedratinib is coadministered with drugs that are dual CYP2C19 and CYP3A4 inhibitors.

Subjects will be screened for eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will return to the clinical site on Day -1 for protocol-specified assessments, and will be domiciled at the clinical site from Day -1 to Day 27.

Being tested
Fedratinib, Fluconazole
Keywords
Healthy adult subjects, Fedratinib, CYP2C19, CYP3A4

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FedratinibDrug

    Fedratinib

  • FluconazoleDrug

    Fluconazole

Study groups in NCT04702464
Study groupRoleWhat they receive
Treatment AdministrationExperimental* Day 1: Single dose of 100 mg fedratinib * Days 10 to 23, inclusive: Single dose of 400 mg fluconazole on Day 10 and once daily (QD) doses of 200 mg fluconazole on Days 11 to 23, inclusive * Day 18: Single dose of 100 mg fedratinib coadministered with the 200-mg fluconazole dose.
Receives: Drug: Fedratinib; Drug: Fluconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetic - Maximum observed plasma concentration (Cmax) for Fedratinib

    Maximum observed plasma concentration

    Measured: Up to 216 hours following the last dose of fedratinib

  2. Pharmacokinetic - Area under the plasma concentration-time curve (AUC) for Fedratinib

    Area under the plasma concentration-time curve

    Measured: Up to 216 hours following the last dose of fedratinib

Secondary outcomes (1)

  1. Incidence of Adverse Events (AEs)

    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-existing condition) should be considered an AE.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jan 2021
  2. Study start12 Jan 2021
  3. Primary completion9 May 2021
  4. Study completion13 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04702464
Sponsor's protocol ID
FEDR-CP-004
Other IDs
U1111-1261-2721
Status last verified
Nov 2021
First submitted
23 Dec 2020
Last updated
29 Nov 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Expanded access
Available

Publications

  • Chen Y, Ogasawara K, Wood-Horrall R, Thomas M, Thomas M, He B, Liu L, Xue Y, Surapaneni S, Carayannopoulos LN, Zhou S, Palmisano M, Krishna G. Effect of fluconazole on the pharmacokinetics of a single dose of fedratinib in healthy adults. Cancer Chemother Pharmacol. 2022 Oct;90(4):325-334. doi: 10.1007/s00280-022-04464-w. Epub 2022 Aug 24.

    PubMed 36001108

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Fedratinib and Fluconazole in people with Healthy Volunteers, run by Celgene at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic - Maximum observed plasma concentration (Cmax) for Fedratinib (time frame: Up to 216 hours following the last dose of fedratinib). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04702464, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2021.

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