Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Fedratinib · 7 trials · 5 indications
Percentage of participants who have ≥ 35% spleen volume reduction (SVR) at end of cycle 6 A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment). The RRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in RRs and 95% confidence interval of the difference for fedratinib to BAT.
Maximum observed plasma concentration
Area under the plasma concentration-time curve
is the highest dose that causes DLTs in not more than 33% of the subjects treated with fedratinib in the first cycle with at least 3 evaluable subjects treated at this dose.
is a recommended Phase 2 dose that is determined as safe and tolerable by the Safety Review Committee based on the data from the first cycle with at least 3 evaluable subjects treated at each dose of the Phase 1 part.
Proportion of subjects who have ≥ 35% SVR at end of Cycle 6 from baseline
Maximum observed plasma concentration
Area under the curve
Renal Clearance
Area under the curve
Estimation of AUC from time zero to the last measured time point
Estimation of AUC from time zero extrapolated to infinity
Estimation of maximum observed plasma concentration
Estimation of time to reach Cmax
Estimation of terminal elimination half-life
Estimation of apparent total plasma clearance when dosed orally
Estimation of apparent volume of distribution when dosed orally
Maximum observed plasma concentration
Time to maximum observed plasma concentration
Area under the curve from time zero to the last quantifiable concentration
Area under the curve from time zero extrapolated to infinity
Terminal elimination half-life
Apparent total plasma clearance when dosed orally
Apparent total volume of distribution when dosed orally
| Arm | Type | Description |
|---|---|---|
| Fedratinib 400mg/day | EXPERIMENTAL | Will include up to 128 subjects receiving fedratinib 400 mg self-administered Investigational Product (IP) on an outpatient basis, once daily preferably together with food during an evening meal at the same time each day in consecutive 4-week (28-day) cycles. |
| Best Available Therapy (BAT) | ACTIVE_COMPARATOR | Best-available Investigator-selected therapy included a number of available compounds to treat MF and/or its symptoms and was chosen by the investigator for each subject. Therapy changed at different times during the treatment period. No investigational agents (e.g. not approved for the treatment of any indication) were allowed. BAT also included the choice of no treatment. |
| Treatment 1A | EXPERIMENTAL | - |
| Treatment 1B | EXPERIMENTAL | - |
| Treatment 2A | EXPERIMENTAL | - |
| Treatment 2B | EXPERIMENTAL | - |
| Treatment 2C | EXPERIMENTAL | - |
| Treatment Administration | EXPERIMENTAL | * 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. |
| Fedratinib Administration | EXPERIMENTAL | The fedratinib dose is 300 or 400 mg/day PO (3 or 4 x 100 mg capsules) to be self-administered orally once daily continuously on an outpatient basis, preferably together with food during an evening meal, the same time each day. |
| Fedratinib in moderate hepatic impairment subjects | EXPERIMENTAL | A single oral dose of 300 mg of fedratinib will be given to subjects with moderate hepatic impairment |
| Fedratinib in severe hepatic impairment subjects | EXPERIMENTAL | A single dose of 200 mg of fedratinib will be given to subjects with severe hepatic impairment |
| Fedratinib in healthy vs moderate hepatic impairment subjects | EXPERIMENTAL | A single oral dose of 300 mg of fedratinib will be given to healthy subjects with normal hepatic function. |
| Fedratinib in healthy vs severe hepatic impairment subjects | EXPERIMENTAL | A single oral dose of 200 mg of fedratinib will be given to healthy subjects with normal hepatic function. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| FEDRATINIB | DRUG | A potent and selective inhibitor of JAK2 kinase activity |
| Best Available Therapy (BAT) | DRUG | Best available therapy (BAT) |
| Fluconazole | DRUG | Fluconazole |
| Digoxin | DRUG | Oral |
| Rosuvastatin | DRUG | Oral |
| Metformin | DRUG | Oral |
| Rifampin | DRUG | Rifampin |
| Efavirenz | DRUG | Efavirenz |
Inclusion Criteria: 1. Subject is at least 18 years of age at the time of signing the informed consent form (ICF) 2. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0, 1 or 2 3. Subject has diagnosis of primary myelofibrosis (PMF) according to the 2016 World Healt...
Fedratinib is being studied for use in primary myelofibrosis and in healthy volunteers. In clinical trials, it is evaluated as a treatment for primary myelofibrosis, while healthy volunteer studies assess its pharmacokinetics, tolerability, and drug interactions. It is an investigational small molecule in Phase 1 clinical development.
Fedratinib is a kinase inhibitor, belonging to the -tinib class of small molecules. It targets kinases, which are enzymes involved in cellular signaling. Its development focuses on conditions like primary myelofibrosis, where kinase activity plays a role in disease pathology.
Fedratinib is developed by Bristol-Myers Squibb Company, traded on the New York Stock Exchange under the ticker BMY. The company is conducting clinical trials to evaluate the drug's safety, tolerability, and pharmacokinetics in various patient populations.
Fedratinib is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities. The ongoing and completed trials focus on pharmacokinetics, tolerability, and drug interactions in healthy volunteers and subjects with hepatic impairment.
Fedratinib has been studied in several Phase 1 trials, including NCT03983161, which evaluated pharmacokinetics in subjects with moderate and severe hepatic impairment, and NCT04231435, which examined its effect on transporter probe substrates. Other completed trials include NCT04702464 and NCT05051553, both in healthy volunteers.
Fedratinib is a distinct small molecule kinase inhibitor developed by Bristol-Myers Squibb. It is not known to be the same as any other drug. Its unique chemical structure and target profile differentiate it from other kinase inhibitors in development.