Healthy VolunteersPhase 1NCT04231435
Influence of Fedratinib on the Pharmacokinetics of the Transporter Probe Substrates Digoxin, Rosuvastatin, and Metformin
A Phase 1 study testing Fedratinib, Digoxin and Rosuvastatin in people with Healthy Volunteers, run by Celgene at 1 site in United States.
Trial 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. 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, Digoxin and Rosuvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Dec 2019to 21 Feb 2020
- 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, 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, 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 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 45 to 100 bpm (inclusive) at screening.
- 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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- 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.
- 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.
- 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 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.
- Subject smokes > 10 cigarettes per day, or equivalent in other tobacco products, more frequently than 8 weeks prior to Screening (self-reported).
- History of multiple drug allergies (ie, 2 or more).
- Allergic to or hypersensitive to any of the drugs used in the study.
- Has any medical condition, medical history, or use of concomitant medication that is contraindicated in the applicable drug labeling.
- Note: Subjects having a history of intolerability or hypersensitivity to selective serotonin reuptake inhibitors, monoamine oxidase-B inhibitors, or serotonin-norepinephrine reuptake inhibitors that are suggestive of serotonin syndrome or related AE are not eligible for study participation.
- 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 palonosetron.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
- Conditions
- Healthy Volunteers
- Being tested
- Fedratinib, Digoxin, Rosuvastatin, Metformin
- Keywords
- Healthy Adult Subjects, Fedratinib, Drug Interactions, Transporters
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FedratinibDrug
Oral
DigoxinDrug
Oral
RosuvastatinDrug
Oral
MetforminDrug
Oral
| Study group | Role | What they receive |
|---|---|---|
| Treatment Administration | Experimental | 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. Receives: Drug: Fedratinib; Drug: Digoxin; Drug: Rosuvastatin; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic - Cmax (Digoxin, Rosuvastatin and Metformin
Maximum observed plasma concentration
Measured: 96 hours
Pharmacokinetic - AUC (Digoxin, Rosuvastatin and Metformin
Area under the curve
Measured: 96 hours
Pharmacokinetic - CLr
Renal Clearance
Measured: 48 hours
Analysis of Glucose AUC after OGTT using linear trapezoidal method
Area under the curve
Measured: 3 hours
Secondary outcomes (1)
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 the time the ICF is signed until study completion and up to 30 days after the last dose of IP
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start18 Dec 2019
- Primary completion19 Feb 2020
- Study completion21 Feb 2020
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
- Sequential
- Masking
- None (open label)
- Enrolment
- 24 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 Carayannopolous, M.D., Study director, Celgene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04231435
- Sponsor's protocol ID
- FEDR-CP-003
- Other IDs
- U1111-1245-6233
- Status last verified
- May 2020
- First submitted
- 14 Jan 2020
- Last updated
- 21 May 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, Wood-Horrall RN, Thomas M, Thomas M, Liu L, Liu M, Xue Y, Surapaneni S, Carayannopoulos LN, Zhou S, Palmisano M, Krishna G. Impact of fedratinib on the pharmacokinetics of transporter probe substrates using a cocktail approach. Cancer Chemother Pharmacol. 2021 Dec;88(6):941-952. doi: 10.1007/s00280-021-04346-7. Epub 2021 Sep 3.
PubMed 34477937
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04231435
- Acronym / sponsor ID
- FEDR-CP-003
- Conditions
- Healthy Volunteers
- Keywords
- Healthy Adult Subjects, Fedratinib, Drug Interactions, Transporters
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Collaborators
- Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation
- Study start
- 18 Dec 2019 (actual)
- Primary completion
- 19 Feb 2020 (actual)
- Study completion
- 21 Feb 2020 (actual)
- First posted
- 18 Jan 2020 (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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Administration | Experimental | Drug: Fedratinib, Drug: Digoxin, Drug: Rosuvastatin, Drug: MetforminAll 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 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 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:
- Females of childbearing potential (FCBP1) must:
Key exclusion criteria (26 listed)
- 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.
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 |
|---|---|---|
| FedratinibOral | Drug | Treatment Administration |
| DigoxinOral | Drug | Treatment Administration |
| RosuvastatinOral | Drug | Treatment Administration |
| MetforminOral | Drug | Treatment Administration |
Primary outcome
Pharmacokinetic - Cmax (Digoxin, Rosuvastatin and Metformin
Time frame: 96 hours
Maximum observed plasma concentration
Pharmacokinetic - AUC (Digoxin, Rosuvastatin and Metformin
Time frame: 96 hours
Area under the curve
Pharmacokinetic - CLr
Time frame: 48 hours
Renal Clearance
Analysis of Glucose AUC after OGTT using linear trapezoidal method
Time frame: 3 hours
Area under the curve
1 secondary outcome
Adverse Events (AEs)
Time frame: From the time the ICF is signed until study completion and up to 30 days after the last dose of IP
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 May 2020.
- Derived from this study: PubMed 34477937Ogasawara K, Wood-Horrall RN, Thomas M, Thomas M, Liu L, Liu M, Xue Y, Surapaneni S, Carayannopoulos LN, Zhou S, Palmisano M, Krishna G. Impact of fedratinib on the pharmacokinetics of transporter probe substrates using a cocktail approach. Cancer Chemother Pharmacol. 2021 Dec;88(6):941-952. doi: 10.1007/s00280-021-04346-7. Epub 2021 Sep 3.
- 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 Carayannopolous, M.D. 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, Digoxin and Rosuvastatin 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 17 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 May 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?
Pharmacokinetic - Cmax (Digoxin, Rosuvastatin and Metformin (time frame: 96 hours). The study lists 4 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 NCT04231435, 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 May 2020.