A Phase 1, Open-label Study to Evaluate the Influence of Fedratinib on the Pharmacokinetics of Transporter Probe Substrates (Digoxin, Rosuvastatin, and Metformin) in Healthy Adult Subjects

Celgene1 site in 1 country24 target enrollmentDecember 18, 2019

ConditionsHealthy Volunteers

InterventionsFedratinib Digoxin Rosuvastatin Metformin

DrugsFedratinib Digoxin Rosuvastatin Metformin

Overview

Phase: Phase 1
Intervention: Fedratinib
Conditions: Healthy Volunteers
Sponsor: Celgene
Enrollment: 24
Locations: 1
Primary Endpoint: Pharmacokinetic - CLr
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a nonrandomized, fixed-sequence, open-label study to evaluate the effect of a single dose of fedratinib on the PK, safety, and tolerability of single doses of digoxin, rosuvastatin, and metformin in healthy subjects. The subjects will participate as follows:

Screening phase
Treatment phase (includes baseline)
Follow-up telephone call Subjects will be screened for eligibility during the screening phase. 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 through the morning of Day 22.

During the study, blood samples will be collected at prespecified times for PK and PD. Urine samples will be collected at prespecified times for urinary PK evaluation of metformin. Subject safety will be monitored throughout the study.

Registry

clinicaltrials.gov

Start Date

December 18, 2019

End Date

February 21, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Celgene

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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:
•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).
•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, as applicable, and after 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 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:

Exclusion Criteria

•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.
•Subject has an estimated glomerular filtration rate (GFR) of \<90 mL/min/1.73 m2 based on the 4-variable Modification of Diet in Renal Disease (MDRD) equation.
•Use of any prescribed systemic or topical medication, including vaccines, within 30 days of the first dose administration (with the exception of any palonosetron 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.

Arms & Interventions

Treatment Administration

All subjects will receive the following oral doses of IP following an overnight fast in the fixed-sequence below: * Day 1 (Period 1): 1 × 0.25-mg digoxin tablet, 1 × 10-mg rosuvastatin tablet, and 1 × 1000-mg metformin tablet. * Day 7 (Period 2): 6 × 100-mg fedratinib capsules PLUS (after approximately 1 hour from the time of fedratinib administration) 1 × 0.25 mg digoxin tablet, 1 × 10-mg rosuvastatin tablet, and 1 × 1000-mg metformin tablet.

Intervention: Fedratinib