Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Glasdegib · 5 trials · 6 indications
AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if the event occurred during the on-treatment period (regardless of if it was seen prior to the start of treatment). An AE was considered treatment related as assigned by the investigator.
A SAE was defined as any untoward medical occurrence that, at any dose that resulted in death; was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or other medical events as per investigator's judgement. A SAE was considered treatment emergent if the event occurred during the on-treatment period (regardless of if it was seen prior to the start of treatment). A SAE was considered treatment related as assigned by the investigator.
OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact.
OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact.
| Arm | Type | Description |
|---|---|---|
| Participants from B1371019 and B1371012 | EXPERIMENTAL | Azacitidine will be administered 75 mg/m2/day for 7 days every 28 days on Days 1-7 (±3 days) per local label or per the IP Manual (or SPC). Azacitidine may be administered by SC injection or IV infusion. Alternate dosing schedules to administer the 7 doses to accommodate participant and treatment center availability are allowed. The starting dose regimen will be the same as the most recent regimen received on the B1371019 or B1371012 study. Glasdegib 50, 75 or 100 mg will be orally administered daily and continuously. The starting dose regimen will be the same as the most recent regimen received on the B1371012 or B1371019 study. |
| Arm A (Intensive Study) | EXPERIMENTAL | Glasdegib + '7+3' Induction(s) |
| Arm B (Intensive Study) | PLACEBO_COMPARATOR | Placebo + '7+3' Induction(s) |
| Arm A (Non-intensive study) | EXPERIMENTAL | Glasdegib + azacitidine |
| Arm B (Non-intensive study) | PLACEBO_COMPARATOR | Placebo + azacitidine |
| Glasdegib Oral tablet then IV | EXPERIMENTAL | Subjects will receive a single 100 mg oral tablet of glasdegib under fasted conditions in the first study period followed by washout. Then in the second period, a 50 mg IV solution will be infused over approximately 1.25 hours under fasted conditions. |
| Glasdegib IV solution followed by Oral tablet | EXPERIMENTAL | Subjects will receive a 50 mg IV solution will be infused over approximately 1.25 hours in the fasted condition followed by washout in the first study period . Then in the second period, a single 100 mg oral tablet of glasdegib will be administered under fasted conditions |
| Glasdegib BE and Food | EXPERIMENTAL | Subjects receive 100 mg single dose of ICH glasdegib under fasted condition with washout and then 100 mg single dose of Phase 2 tablet under fasted condition with washout in a randomized fashion. Finally subjects receive a 100 mg single dose ICH tablet after a high fat, high calorie meal. |
| Glasdegib BE and PPI Effect | EXPERIMENTAL | Subjects receive 100 mg single dose of ICH glasdegib under fasted condition with washout and then 100 mg single dose of Phase 2 tablet under fasted condition with washout in a randomized fashion. Finally subjects receive a 100 mg single dose ICH tablet in the fasted state after repeated daily dosing with rabeprazole. |
| Glasdegib, Rifampin | EXPERIMENTAL | Subjects receive a 100mg oral dose of glasdegib under fasted conditions with washout, then single 100mg oral dose of glasdegib under fasted following dosing to steady state with rifampin |
| Name | Type | Description |
|---|---|---|
| Glasdegib | DRUG | 25 mg or 100 mg tablet |
| Azacitidine | DRUG | 100 mg/vial powder for 25 mg/mL suspension for injection |
| daunorubicin + cytarabine | DRUG | '7+3' (cytarabine 100 mg/m2, IV for 7 days by continuous infusion and daunorubicin 60 mg/m2 for 3 days). If a second induction is needed, Investigators may choose either a 5 day cytarabine continuous infusion plus daunorubicin for 2 days ('5+2') or a 7 day cytarabine continuous infusion plus daunorubicin for 3 days ('7+3'); |
| Placebo | DRUG | Matching placebo (PO) given on Day 1 and is to continue up to 2 years post randomization. Following consolidation therapy, placebo will be administered daily for up to 2 years after randomization or until they have MRD negative disease, whichever comes first. Daily placebo will continue throughout Induction(s) and Consolidation therapies regardless of dose modifications/delays in the chemotherapy. |
| cytarabine | DRUG | Consolidation with single agent cytarabine 3 g/m2 IV for adults \<60 years and 1 g/m2 for adults 60 years over 3 BID on Days 1, 3, and 5, every 28 days for up to 4 cycles or alternative single agent cytarabine consolidation schedules may be used per local prescribing information. |
| HSCT | PROCEDURE | If required, and done per standard of care post Induction(s). |
| Glasdegib Oral Tablet | DRUG | Subjects will receive a single 100 mg oral tablet of glasdegib under fasted conditions, either in study period 1 or 2, depending on randomization. |
| Glasdegib IV infusion | DRUG | Subjects will receive a 50 mg IV infusion of glasdegib over approximately 1.25 hours, in the fasted state, in either period 1 or 2 based on randomization. |
| High Fat, High Calorie Meal | OTHER | A subset of subjects in the study will receive a high fat, high calorie meal prior to being administered a single 100 mg tablet ICH tablet of glasdegib. |
| Rabeprazole | DRUG | A subset of subjects will receive repeated daily dosing of 40 mg rabeprazole for 7 days with 100 mg single dose of ICH glasdegib being administered on Day 7. |
| Rifampin | DRUG | Subjects receive rifampin 600 mg oral dose daily \[Day -6 to day 4\] |
Inclusion Criteria: * Any participant who continues to demonstrate clinical benefit (as determined by the Principal Investigator) from study treatment with azacitidine with or without glasdegib in this Study or from Study B1371012. * Capable of giving signed informed consent as described in Appendi...
Glasdegib is an investigational small molecule being studied for the treatment of Acute Myeloid Leukemia (AML). It has also been evaluated in clinical trials involving healthy volunteers and patients with hepatic impairment. The drug is being developed by Pfizer, Inc. and is currently in Phase 3 clinical development.
Glasdegib is a small molecule that targets the Hedgehog signaling pathway. It works by inhibiting the Smoothened receptor, which is a key component of this pathway. By blocking this receptor, Glasdegib aims to disrupt signaling that can promote cancer cell growth and survival in conditions like Acute Myeloid Leukemia.
Glasdegib is being developed by Pfizer, Inc., a multinational pharmaceutical company. Pfizer is listed on the New York Stock Exchange under the ticker symbol PFE. The company is conducting clinical trials to evaluate the safety and efficacy of Glasdegib for the treatment of Acute Myeloid Leukemia and other conditions.
Glasdegib is currently in Phase 3 clinical development. It has completed two Phase 3 trials, including a study evaluating intensive chemotherapy with or without Glasdegib in patients with previously untreated Acute Myeloid Leukemia. The drug is investigational and has not yet been approved by regulatory authorities.
Glasdegib has been studied in several clinical trials, including NCT03416179, a Phase 3 study of intensive chemotherapy with or without Glasdegib in previously untreated Acute Myeloid Leukemia. Other trials include NCT02430545 and NCT03627754, which evaluated the drug's pharmacokinetics in healthy volunteers and patients with hepatic impairment, respectively.
Glasdegib is also known by the brand name Daurismo. This alternative name is used in some contexts to refer to the same drug. Both names refer to the investigational small molecule being developed by Pfizer for the treatment of Acute Myeloid Leukemia.