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Voxelotor

Phase 3

Sickle Cell Disease | Small molecule | Hematology |Pfizer, Inc.|Last Updated: Nov 22, 2024

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials5
Total Enrollment548

FDA Designations

No designations recorded

Clinical trial landscape

Voxelotor · 5 trials · 1 indication

Phase 3 1Phase 2 1Phase 1 3
NCT03036813Study to Evaluate the Effect of Voxelotor Administered Orally to Patients With Sickle Cell Disease (GBT_HOPE)Sickle Cell Disease
COMPLETED449 Analytics
PHASE3COMPLETED
Study to Evaluate the Effect of Voxelotor Administered Orally to Patients With Sickle Cell Disease (GBT_HOPE)
Sickle Cell DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants With Increase in Hb >1 g/dL From Baseline to Week 24
Baseline to Week 24

Number of participants with increase in Hb \>1 g/dL from Baseline to Week 24

Part A: Maximum Observed Plasma Concentration (Cmax) for Bupropion
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively
Part A: Cmax for Repaglinide
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Period 1 Day 4 and Period 2 Day 6 for Treatment B and F, respectively
Part A: Cmax for Flurbiprofen
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively
Part A: Cmax for Omeprazole
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively
Part A: Cmax for Midazolam
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively
Part A: Area Under the Plasma Concentration-Time Curve From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUCt) for Bupropion
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

AUCt was calculated using the linear/log trapezoidal rule.

Part A: AUCt for Repaglinide
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Period 1 Day 4 and Period 2 Day 6 for Treatment B and F, respectively

AUCt was calculated using the linear/log trapezoid rule.

Part A: AUCt for Flurbiprofen
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

AUCt was calculated using the linear/log trapezoid rule.

Part A: AUCt for Omeprazole
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

AUCt was calculated using the linear/log trapezoid rule.

Part A: AUCt for Midazolam
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

AUCt was calculated using the linear/log trapezoid rule.

Part A: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) for Bupropion
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

Part A: AUCinf for Repaglinide
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Period 1 Day 4 and Period 2 Day 6 for Treatment B and F, respectively

AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

Part A: AUCinf for Flurbiprofen
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

Part A: AUCinf for Omeprazole
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

Part A: AUCinf for Midazolam
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

Part B: Cmax for Metformin
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively
Part B: Cmax for Furosemide
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively
Part B: Cmax for Rosuvastatin
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively
Part B: AUCt for Metformin
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

AUCt was calculated using the linear/log trapezoid rule.

Part B: AUCt for Furosemide
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

AUCt was calculated using the linear/log trapezoid rule.

Part B: AUCt for Rosuvastatin
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Day 1 and Day 4 for Treatment A and Treatment C, respectively

AUCt was calculated using the linear/log trapezoid rule.

Part B: AUCinf for Metformin
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

Part B: AUCinf for Furosemide
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

Part B: AUCinf for Rosuvastatin
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

Secondary Endpoints

Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate
Baseline to Week 72
Percentage Change From Baseline in Hemolysis Measures
Baseline to Week 24
Part A: Cmax for 6-Hydroxybupropion
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Dose 1ACTIVE_COMPARATORvoxelotor
Dose 2ACTIVE_COMPARATORvoxelotor
PlaceboPLACEBO_COMPARATORPlacebo
Part AEXPERIMENTALTo evaluate the effect of multiple doses of voxelotor on the plasma pharmacokinetics (PK) of a single dose of bupropion, repaglinide, flurbiprofen, omeprazole, and midazolam
Part BEXPERIMENTALTo evaluate the effect of multiple doses of voxelotor on the plasma PK of a single dose of metformin, furosemide, and rosuvastatin

Interventions

NameTypeDescription
voxelotorDRUG -
PlaceboOTHER -
GBT440DRUGOral drug
BupropionDRUGDrug drug interaction
RepaglinideDRUGDrug drug interaction
FlurbiprofenDRUGDrug drug interaction
OmeprazoleDRUGDrug drug interaction
MidazolamDRUGDrug drug interaction
MetforminDRUGDrug drug interaction
FurosemideDRUGDrug drug interaction
RosuvastatinDRUGDrug drug interaction
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Eligibility Criteria

Age Range12 Years to 65 Years
SexALL
Healthy VolunteersNo
Study Sites62

Inclusion Criteria: 1. Male or female study participants with sickle cell disease 2. Participants have had at least 1 episode of vaso-occlusive crisis (VOC) in the past 12 months. 3. Age 12 to 65 years 4. Hemoglobin (Hb) ≥5.5 and ≤10.5 g/dL during screening 5. For participants taking hydroxyurea (H...

Countries:United StatesCanadaEgyptFranceItalyJamaicaKenyaLebanonNetherlandsOmanTurkey (Türkiye)United Kingdom
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Frequently asked questions about Voxelotor

What is GBT440 used for?

GBT440 is an investigational small molecule being studied for sickle cell disease, anemia of sickle cell disease, and idiopathic pulmonary fibrosis with hypoxemia. It has also been evaluated in healthy subjects for pharmacokinetic studies. The drug is in clinical development and is not approved by the FDA.

Who makes GBT440?

GBT440 is being developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker PFE. Pfizer is the sponsor of the clinical trials for this investigational drug.

What phase is GBT440 in?

GBT440 has been studied in Phase 1 and Phase 2 clinical trials. The Phase 2 trial evaluated the drug in patients with idiopathic pulmonary fibrosis and hypoxemia. All five clinical trials for GBT440 have been completed, and the drug remains investigational.

What clinical trials is GBT440 in?

GBT440 has been studied in five completed clinical trials. These include NCT02497924, a study of absorption, metabolism, and excretion in healthy subjects; NCT02567695, a bioavailability study in healthy subjects; NCT02846324, a safety and tolerability study in patients with idiopathic pulmonary fibrosis; and NCT05981365, a drug interaction study in healthy subjects.

Is GBT440 the same as voxelotor?

GBT440 is also known as voxelotor. One of its clinical trials, NCT05981365, is titled "Voxelotor CYP and Transporter Cocktail Interaction Study," confirming that GBT440 and voxelotor refer to the same drug.