Healthy VolunteersPhase 1NCT03983239
Effect of Rifampin and Efavirenz on the Pharmacokinetics of Fedratinib in Healthy Adult Subjects
A Phase 1 study testing Fedratinib, Rifampin and Efavirenz in people with Healthy Volunteers, run by Celgene at 1 site in United States.
Trial summary
This is a 2-part study to evaluate the effect of multiple doses of rifampin or efavirenz on the PK, safety, and tolerability of single doses of fedratinib in healthy subjects. Each study part will consist of a nonrandomized, fixed-sequence, open-label design. The study parts can be run in any order or in parallel. 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, Rifampin and Efavirenz
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jun 2019to 6 Nov 2019
- 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 to adhere to the study visit schedule and other protocol requirements.
- Subject must be a male or female of any race from ≥ 18 and ≤ 65 years of age at the time of signing the informed Consent Form (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 (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 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:
- 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, during any dose interruptions, 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 ECG at screening and check-in (Day -1), as applicable:
- Aspartate aminotransferase (AST), alanine aminotransferase (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 one time during the screening period and up to one 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 140 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 40 to 100 bpm (inclusive) at screening. Repeat vital signs may be measured at investigator discretion.
- 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 two 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 (ie, within 3 years) 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, severe ataxia, ocular paralysis, or cerebellar signs) without documented exclusion of WE by thiamine level and brain MRI.
- Subject has thiamine deficiency, defined as thiamine levels in whole blood below normal range according to institutional standard.
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- Subject has active tuberculosis or another disease caused by mycobacteria.
- Use of any prescribed systemic or topical medication, including vaccines, within 30 days of the first dose administration (with the exception of any odansetron 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 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. 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). Appendectomy and cholecystectomy are 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.
- History of alcohol abuse (as defined by the current version of the DSM) within 2 years before dosing or positive alcohol screen.
- Known to have serum hepatitis; known to be a carrier of the hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), or hepatitis C antibody (HCV Ab); have a positive result to the test for hepatitis B or hepatitis C virus at screening or have a positive result to the test for human immunodeficiency virus (HIV) antibodies at screening. Subjects whose results are compatible with prior immunization (including natural and vaccination) against hepatitis B may be included at the discretion of the investigator.
- Use of tobacco- or nicotine-containing products within 3 months prior to check-in.
- Subject has received live vaccination (excluding seasonal flu vaccination) within 90 days of first dosing.
- History of multiple drug allergies (ie, two or more).
- Allergic to or hypersensitive to any of the drugs used in the part of the study in which the subject will participate.
- Has any medical condition, medical history, or use of concomitant medication that is contraindicated in the applicable drug labeling.
- Female subject who is pregnant or breastfeeding.
- Subject is part of the clinical staff personnel or a family member of the clinical site staff.
- Subject has a hypersensitivity to ondansetron.
- History of severe or serious psychiatric disease ever requiring hospitalization or use of antipsychotic/neuroleptic medications, history of suicidal ideation or suicidal attempt, or undergoing psychiatric treatment will be excluded from study participation.
- Subject deemed by the investigator or medical professional to be a fall risk.
Trial locations and contacts
1 site in 1 country.
United States1 site
Covance Clinical Research Unit Inc - Dallas
Dallas, Texas, 75247
About this study
Official title: A Phase 1, Open-label, 2-part Study to Evaluate the Effect of Rifampin and Efavirenz on the Pharmacokinetics of Fedratinib in Healthy Adult Subjects
This is a 2-part study to evaluate the effect of multiple doses of rifampin or efavirenz on the PK, safety, and tolerability of single doses of fedratinib in healthy subjects. Each study part will consist of a nonrandomized, fixed-sequence, open-label design. The study parts can be run in any order or in parallel. Subjects may participate in one part only. For each part, subjects will participate as follows:
- Screening
- Treatment period (includes baseline)
- Follow-up telephone call (4 days [± 2 days] after discharge) During the study, blood samples will be collected at prespecified times for PK. Subject safety will be monitored throughout the study.
- Conditions
- Healthy Volunteers
- Being tested
- Fedratinib, Rifampin, Efavirenz
- Keywords
- Healthy Subject, Fedratinib, Rifampin, Efavirenz, Drug Interaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FedratinibDrug
Fedratinib
RifampinDrug
Rifampin
EfavirenzDrug
Efavirenz
| Study group | Role | What they receive |
|---|---|---|
| Fedratinib plus Rifampin | Experimental | A single dose of fedratinib on Day 1. On Days 9 through 18, once-daily (QD) doses of rifampin. On Day 17, a single dose of fedratinib will be concomitantly administered with rifampin. Receives: Drug: Fedratinib; Drug: Rifampin; Drug: Efavirenz |
| Fedratinib plus Efavirenz | Experimental | A single dose of fedratinib on Day 1. On Days 9 through 18, once-daily (QD) doses of efavirenz. On Day 17, a single dose of fedratinib will be concomitantly administered with efavirenz. Receives: Drug: Fedratinib; Drug: Rifampin; Drug: Efavirenz |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fedratinib Pharmacokinetic - Cmax
Maximum observed plasma concentration
Measured: Up to approximately 8 days.
Fedratinib Pharmacokinetic - Tmax
Time to maximum observed plasma concentration
Measured: Up to approximately 8 days.
Fedratinib Pharmacokinetic - AUC0-t
Area under the curve from time zero to the last quantifiable concentration
Measured: Up to approximately 8 days.
Fedratinib Pharmacokinetic - AUC0-∞
Area under the curve from time zero extrapolated to infinity
Measured: Up to approximately 8 days.
Fedratinib Pharmacokinetic - t1/2
Terminal elimination half-life
Measured: Up to approximately 8 days.
Fedratinib Pharmacokinetic - CL/F
Apparent total plasma clearance when dosed orally
Measured: Up to approximately 8 days.
Fedratinib Pharmacokinetic - Vz/F
Apparent total volume of distribution when dosed orally
Measured: Up to approximately 8 days.
Secondary outcomes (1)
Adverse Events (AEs)
Number of participants with an adverse event.
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.
- First posted12 Jun 2019
- Study start21 Jun 2019
- Primary completion2 Nov 2019
- Study completion6 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Leon Carayannopoulos, MD, Study director, Celgene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03983239
- Sponsor's protocol ID
- FEDR-CP-002
- Other IDs
- U1111-1233-7946
- Status last verified
- Aug 2020
- First submitted
- 3 Jun 2019
- Last updated
- 21 Aug 2020
- 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
Ogasawara K, Kam J, Thomas M, Liu L, Liu M, Xue Y, Surapaneni S, Carayannopoulos LN, Zhou S, Palmisano M, Krishna G. Effects of strong and moderate CYP3A4 inducers on the pharmacokinetics of fedratinib in healthy adult participants. Cancer Chemother Pharmacol. 2021 Sep;88(3):369-377. doi: 10.1007/s00280-021-04292-4. Epub 2021 May 21.
PubMed 34019108
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, 2-part Study to Evaluate the Effect of Rifampin and Efavirenz on the Pharmacokinetics of Fedratinib in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT03983239
- Acronym / sponsor ID
- FEDR-CP-002
- Conditions
- Healthy Volunteers
- Keywords
- Healthy Subject, Fedratinib, Rifampin, Efavirenz, Drug Interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Collaborators
- Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation
- Study start
- 21 Jun 2019 (actual)
- Primary completion
- 2 Nov 2019 (actual)
- Study completion
- 6 Nov 2019 (actual)
- First posted
- 12 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 2-part study to evaluate the effect of multiple doses of rifampin or efavirenz on the PK, safety, and tolerability of single doses of fedratinib in healthy subjects. Each study part will consist of a nonrandomized, fixed-sequence, open-label design. The study parts can be run in any order or in parallel. Subjects may participate in one part only. For each part, subjects will participate as follows:
- Screening
- Treatment period (includes baseline)
- Follow-up telephone call (4 days [± 2 days] after discharge) During the study, blood samples will be collected at prespecified times for PK. Subject safety will be monitored throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fedratinib plus Rifampin | Experimental | Drug: Fedratinib, Drug: Rifampin, Drug: EfavirenzA single dose of fedratinib on Day 1. On Days 9 through 18, once-daily (QD) doses of rifampin. On Day 17, a single dose of fedratinib will be concomitantly administered with rifampin. |
| Fedratinib plus Efavirenz | Experimental | Drug: Fedratinib, Drug: Rifampin, Drug: EfavirenzA single dose of fedratinib on Day 1. On Days 9 through 18, once-daily (QD) doses of efavirenz. On Day 17, a single dose of fedratinib will be concomitantly administered with efavirenz. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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 to adhere to the study visit schedule and other protocol requirements.
- Subject must be a male or female of any race from ≥ 18 and ≤ 65 years of age at the time of signing the informed Consent Form (ICF).
- Female subjects NOT of childbearing potential must:
- Females of childbearing potential (FCBP) must:
Key exclusion criteria (26 listed)
- History (ie, within 3 years) 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, severe ataxia, ocular paralysis, or cerebellar signs) without documented exclusion of WE by thiamine level and brain MRI.
- Subject has thiamine deficiency, defined as thiamine levels in whole blood below normal range according to institutional standard.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FedratinibFedratinib | Drug | Fedratinib plus Efavirenz, Fedratinib plus Rifampin |
| RifampinRifampin | Drug | Fedratinib plus Efavirenz, Fedratinib plus Rifampin |
| EfavirenzEfavirenz | Drug | Fedratinib plus Efavirenz, Fedratinib plus Rifampin |
Primary outcome
Fedratinib Pharmacokinetic - Cmax
Time frame: Up to approximately 8 days.
Maximum observed plasma concentration
Fedratinib Pharmacokinetic - Tmax
Time frame: Up to approximately 8 days.
Time to maximum observed plasma concentration
Fedratinib Pharmacokinetic - AUC0-t
Time frame: Up to approximately 8 days.
Area under the curve from time zero to the last quantifiable concentration
Fedratinib Pharmacokinetic - AUC0-∞
Time frame: Up to approximately 8 days.
Area under the curve from time zero extrapolated to infinity
Fedratinib Pharmacokinetic - t1/2
Time frame: Up to approximately 8 days.
Terminal elimination half-life
Fedratinib Pharmacokinetic - CL/F
Time frame: Up to approximately 8 days.
Apparent total plasma clearance when dosed orally
Fedratinib Pharmacokinetic - Vz/F
Time frame: Up to approximately 8 days.
Apparent total volume of distribution when dosed orally
1 secondary outcome
Adverse Events (AEs)
Time frame: From enrollment until at least 30 days after completion of study treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2020.
- Derived from this study: PubMed 34019108Ogasawara K, Kam J, Thomas M, Liu L, Liu M, Xue Y, Surapaneni S, Carayannopoulos LN, Zhou S, Palmisano M, Krishna G. Effects of strong and moderate CYP3A4 inducers on the pharmacokinetics of fedratinib in healthy adult participants. Cancer Chemother Pharmacol. 2021 Sep;88(3):369-377. doi: 10.1007/s00280-021-04292-4. Epub 2021 May 21.
- Individual participant dataSharing planned: 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/
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Screening Protocol
Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leon Carayannopoulos, MD study director
Celgene
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fedratinib, Rifampin and Efavirenz 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 26 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 21 Aug 2020. 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?
Fedratinib Pharmacokinetic - Cmax (time frame: Up to approximately 8 days.). The study lists 7 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 NCT03983239, 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 21 Aug 2020.