A Relative Bioavailability Study Evaluating Two New Encorafenib Formulations (ERBA)

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Encorafenib capsule formulation (CAP); Drug: Encorafenib first formulation; Drug: Encorafenib second formulation; Drug: Rabeprazole tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT05446142

C4221024

Details and patient eligibility

About

Relative bioavailability study to evaluate the pharmacokinetics of two new encorafenib formulations

Full description

In order to decrease the size of the current formulated encorafenib capsule and improve the physical stability, 2 new encorafenib tablet formulations have been developed.

This study is intended to select the optimal tablet formulation for commercialization based on the tablet pharmacokinetics.

A preliminary assessment of the effect of a proton-pump inhibitor on the pharmacokinetics of the 2 encorafenib tablet formulations will also be conducted to assist in the formulation selection.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Participants must be male or female of non-childbearing potential of 18 years of age or older, inclusive, at the time of signing the informed consent document.
• Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Body Mass Index of 17.5 to 30.5 kg/meters squared; and a body weight >50 kg (110 lb).
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent document and the protocol.

Exclusion criteria

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease. Evidence of any active and uncontrolled bacterial or viral infection.
• Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
• History of human immunodeficiency virus infection, hepatitis B, or hepatitis C; positive testing for human immunodeficiency virus, Hepatitis B surface antigen, Hepatitis B core antibody or hepatitis C virus antibody. Hepatitis B vaccination is allowed.
• Positive COVID-19 test at first admission.
• Other medical or psychiatric conditions, laboratory test abnormalities, other conditions or situations related to COVID-19 pandemic or, in the investigator's judgment, make the participant inappropriate for the study.
• Use of prescription or non-prescription medications within 7 days prior to the first dose of encorafenib with the exception of moderate/potent CYP3A inducers which are prohibited within 14 days plus 5 half-lives prior to the first dose.
• History of known sensitivity to rabeprazole, substituted benzimidazoles or to any component of the rabeprazole formulation.
• Previous administration with an investigational product (drug or vaccine) within 30 days.
• Known hypersensitivity to encorafenib or its excipients.
• A positive urine drug or cotinine test.
• Screening supine blood pressure ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest.
• Baseline standard 12 lead electrocardiogram that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
• Aspartate transaminase or alanine aminotransferase level ≥ 1.5 × upper limit of normal.
• Total bilirubin level ≥1.5 × upper limit of normal.
• Estimated glomerular filtration rate <60 ml/min/1.73 m2

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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18 participants in 2 patient groups

Four Period Treatment Sequence: PPI Effect

Experimental group

Description:

Participants will receive a single encorafenib dose formulation, a single encorafenib dose of the formulated capsule (CAP), and a single encorafenib dose of the formulation after administration of 20 mg rabeprazole every evening for 5 days.

Treatment:

Drug: Encorafenib capsule formulation (CAP)

Drug: Encorafenib first formulation

Drug: Encorafenib second formulation

Drug: Rabeprazole tablet

Four Period Treatment Sequence: PPI Effect Second Formulation

Experimental group

Description:

Participants will receive a single encorafenib dose of the second formulation, a single encorafenib dose of the second formulation, a single encorafenib dose of the formulated capsule (CAP), and a single encorafenib dose of the second formulation after administration of 20 mg rabeprazole every evening for 5 days.

Treatment:

Drug: Encorafenib capsule formulation (CAP)

Drug: Encorafenib first formulation

Drug: Encorafenib second formulation

Drug: Rabeprazole tablet