A Relative Bioavailability Study Evaluating Two New Encorafenib Formulations

Pfizer18 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

Encorafenib capsule formulation (CAP)DRUG

A single encorafenib dose of the CAP formulation

Encorafenib first formulationDRUG

first formulation

Encorafenib second formulationDRUG

second formulation

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

New Haven Clinical Research Unit

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinite Time (AUCinf) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole

AUCinf for encorafenib eMCC, eMCCL and CAP formulations (75 mg, single dose administration), and for encorafenib eMCC and eMCCL formulations (75 mg, single dose administration) following 5 days of rabeprazole 20 mg daily were calculated by AUClast + (Clast/kel), where AUClast was the area under the plasma concentration-time profile from time zero to last quantifiable concentration, Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was first-order elimination rate constant.

Time frame: Day 1 predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose

Maximum Observed Plasma Concentration (Cmax) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole

Cmax for encorafenib eMCC, eMCCL and CAP formulations (75 mg, single dose administration), and for encorafenib eMCC and eMCCL formulations (75 mg, single dose administration) following 5 days of rabeprazole 20 mg daily were observed directly from data.

Time frame: Day 1 predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose

Area Under the Plasma Concentration-Time Profile From Time Zero to Last Quantifiable Concentration (AUClast) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole

AUClast for encorafenib eMCC, eMCCL and CAP formulations (75 mg, single dose administration), and for encorafenib eMCC and eMCCL formulations (75 mg, single dose administration) following 5 days of rabeprazole 20 mg daily were calculated using Linear/Log trapezoidal method.

Time frame: Day 1 predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose

Secondary Outcomes

Time for Cmax (Tmax) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole

Tmax for encorafenib eMCC, eMCCL and CAP formulations (75 mg, single dose administration), and for encorafenib eMCC and eMCCL formulations (75 mg, single dose administration) following 5 days of rabeprazole 20 mg daily were observed directly from data as time of first occurrence.

Data from ClinicalTrials.gov

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