Clinical trial NCT05446142: A Relative Bioavailability Study Evaluating Two New Encorafenib Formulations
Official title: A PHASE 1, RANDOMIZED, OPEN-LABEL STUDY IN HEALTHY PARTICIPANTS TO ESTIMATE THE BIOAVAILABILITY OF TWO NEW ENCORAFENIB FORMULATIONS RELATIVE TO THE CURRENT FORMULATION AND TO EVALUATE THE EFFECT OF A PROTON-PUMP INHIBITOR ON ENCORAFENIB PLASMA PHARMACOKINETICS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Encorafenib
Rabeprazole
Healthy adult participants
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
name: Pierre Fabre Laboratories
First posted: 2022-07-06
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Day 1 predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose
measure: Maximum Observed Plasma Concentration (Cmax) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole
timeFrame: Day 1 predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose
measure: 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
timeFrame: 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:
measure: Time for Cmax (Tmax) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole
timeFrame: Day 1 predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose
measure: Terminal Half-Life (t½) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole
timeFrame: Day 1 predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose
measure: Apparent Clearance (CL/F) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole
timeFrame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose
measure: Apparent Volume of Distribution (Vz/F) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole
timeFrame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 28 after the last encorafenib dose (the total duration of the study was approximately 60 days from baseline)
measure: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
timeFrame: Baseline, and at early discontinuation or at the discretion of the investigator (the total duration of the study was approximately 60 days from baseline)
measure: Number of Participants Meeting Vital Signs Categorical Criteria
timeFrame: Baseline, 0 and 2 hours postdose in each period, and at early discontinuation (the total duration of the study was approximately 60 days from baseline)
measure: Number of Participnts With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline, 0 and 2 hours postdose in each period, and at early discontinuation (the total duration of the study was approximately 60 days from baseline)
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: