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

• ClinicalTrials.gov Identifier: NCT05446142
• Recruitment Status: Completed
• First Posted: July 6, 2022
• Results First Posted: February 23, 2024
• Last Update Posted: February 23, 2024
• Sponsor: Pfizer
• Collaborators: Ono Pharmaceutical Co. Ltd; Pierre Fabre Laboratories
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: July 1, 2022
• First Posted Date: July 6, 2022
• Results First Submitted Date: July 24, 2023
• Results First Posted Date: February 23, 2024
• Last Update Posted Date: February 23, 2024
• Actual Study Start Date: July 1, 2022
• Actual Primary Completion Date: September 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 24, 2023)

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

Original Primary Outcome Measures (submitted: July 1, 2022)

• Plasma AUCinf after administration of the first formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
  Area under the plasma concentration-time profile from time zero extrapolated to infinite time
• Plasma Cmax after administration of the first formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
  Maximum plasma concentration
• Plasma AUClast after administration of the first formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
  Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (Clast)
• Plasma AUCinf of the second formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
  Area under the plasma concentration-time profile from time zero extrapolated to infinite time
• Plasma Cmax after administration of the second formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
  Maximum plasma concentration
• Plasma AUClast after administration of the second formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
  Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (Clast)
• Plasma AUCinf after administration of the CAP (encorafenib formulated capsule) formulation [ Time Frame: Day 1, Pre-dose, hour 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
  Area under the plasma concentration-time profile from time zero extrapolated to infinite time
• Plasma Cmax after administration of the CAP formulation [ Time Frame: Day 1, Pre-dose, hour 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
  Maximum plasma concentration
• Plasma AUClast after administration of the CAP formulation [ Time Frame: Day 1, Pre-dose, hour 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
  Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (Clast)
• Plasma AUCinf of the first formulation after 5 days of 20 mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hour 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
  Area under the plasma concentration-time profile from time zero extrapolated to infinite time
• Plasma Cmax of the first formulation after 5 days of 20 mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hour 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
  Maximum plasma concentration
• Plasma AUClast of the first formulation after 5 days of 20 mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hour 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
  Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (Clast)
• Plasma AUCinf of the second formulation after 5 days of 20 mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hour 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
  Area under the plasma concentration-time profile from time zero extrapolated to infinite time
• Plasma Cmax of the second formulation after 5 days of 20 mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hour 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
  Maximum plasma concentration
• Plasma AUClast of the second formulation after 5 days of 20 mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hour 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
  Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (Clast)

Current Secondary Outcome Measures (submitted: July 24, 2023)

• Time for Cmax (Tmax) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole [ 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 ]
  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.
• Terminal Half-Life (t½) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole [ 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 ]
  t½ 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 Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
• Apparent Clearance (CL/F) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole [ Time Frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose ]
  CL/F 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 Dose/AUCinf after oral dose.
• Apparent Volume of Distribution (Vz/F) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole [ Time Frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose ]
  Vz/F 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 Dose/(AUCinf * kel) after oral dose.
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Day 28 after the last encorafenib dose (the total duration of the study was approximately 60 days from baseline) ]
  An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Any AEs occurring following start of treatment were considered as treatment emergent adverse event (TEAE). Events that occurred during follow-up within the lag time of up to 28 days after the last encorafenib dose were counted as treatment emergent and attributed to the last treatment taken. Events that occurred during the washout period (up to 28 days from the last treatment) between study periods were counted as treatment emergent and attributed to the previous treatment taken.
• Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality [ Time Frame: Baseline, and at early discontinuation or at the discretion of the investigator (the total duration of the study was approximately 60 days from baseline) ]
  Haematological, clinical chemistry (serum) and urinalysis safety tests were assessed against the criteria specified in the sponsor reporting standards. The assessment did not take into account whether each participants's baseline test result was within or outside the laboratory reference range for the particular laboratory parameter. The baseline measurement for safety laboratory tests for all periods was the predose measurement on Day -1 of Period 1. Only those categories in which at least 1 participant had data were reported.
• Number of Participants Meeting Vital Signs Categorical Criteria [ Time Frame: 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) ]
  Supine blood pressure (BP) and pulse rate (PR) were measured at times specified. For Periods 1 to 3, the baseline measurement was the predose measurement on Day -1 of each period. For Period 4, the baseline measurement was the predose measurement on Day -1 of Period 3. The reported categories included: systolic blood pressure (SBP)>=90mmHg; change from baseline (CFB) in SBP>=30mmHg; diastolic blood pressure (DBP)<50mmHg; CFB in DBP>=20mmHg; PR<40 beats per minute (bpm) or PR>120bpm. Only those categories in which at least 1 participant had data were provided.
• Number of Participnts With Clinically Significant Electrocardiogram (ECG) Abnormalities [ Time Frame: 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) ]
  Absolute values and changes from baseline in PR, QT, QRS, heart rate and QTcF were summarized by protocol pre-defined categorization criterion. QTcF were derived using Fridericia's heart rate correction formula. For each period, triplicate ECGs were conducted predose on Day 1; all other ECG measurements were single ECGs. The baseline ECG value was the average of the triplicate ECG measurements collected before dose administration on Day 1. Changes from baseline were defined as the change between the postdose ECG measurement and the derived baseline ECG.

Original Secondary Outcome Measures (submitted: July 1, 2022)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Time the participant provides informed consent through and including a minimum of 28 calendar days after the last administration of the study intervention. ]
  An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. SAE is defined as one of the following: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant; requires inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AE is defined as an AE with onset date occurring during the on-treatment period. AEs include all SAEs and non-SAEs.
• Number of Participants With Clinically Significant Change From Baseline in Vital Signs [ Time Frame: Baseline through Period 4 ]
  Vital signs (body temperature, respiratory rate, radial pulse, systolic and diastolic blood pressure) will be obtained with participant in the seated position, after having sat calmly for at least 5 minutes.
• Number of Participants With Electrocardiogram (ECG) Abnormalities [ Time Frame: Baseline through Period 4 (period 4 is defined as Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48) ]
  ECG abnormalities criteria include a) a postdose QTcF is increased by ≥60 ms from the baseline and is >450 ms; or b) an absolute QTcF value is ≥500 ms for any scheduled ECG
• Number of Participants With Laboratory Test Abnormalities [ Time Frame: ≤ 28 days pre-dose, screening and discharge Period 1-4 ]
  Following parameters will be analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein); urinalysis.
• Time to Reach Maximum Observed Plasma Concentration (Tmax) after administration of the first formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
• Plasma Decay Half-Life (t1/2) after administration of the first formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
• Apparent Oral Clearance (CL/F) after administration of the first formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
• Apparent Volume of Distribution (Vz/F) after administration of the first formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) after administration of the second formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
• Plasma Decay Half-Life (t1/2) after administration of the second formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
• Apparent Oral Clearance (CL/F) after administration of the second formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
• Apparent Volume of Distribution (Vz/F) after administration of the second formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Periods 1-3) ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) after administration of the first formulation after 5 days of 20mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
• Plasma Decay Half-Life (t1/2) after administration of the first formulation after 5 days of 20mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
• Apparent Oral Clearance (CL/F) after administration of the first formulation after 5 days of 20mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
• Apparent Volume of Distribution (Vz/F) after administration of the first formulation after 5 days of 20mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
• Time to Reach Maximum Observed Plasma Concentration Plasma after administration of the second formulation after 5 days of 20mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
• Plasma Decay Half-Life (t1/2) after administration of the second formulation after 5 days of 20mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
• Apparent Oral Clearance (CL/F) after administration of the second formulation after 5 days of 20mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
• Apparent Volume of Distribution (Vz/F) after administration of the second formulation after 5 days of 20mg daily rabeprazole dosing [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 4) ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) after administration of the CAP formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 1-3) ]
• Plasma Decay Half-Life (t1/2) after administration of the CAP formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 1-3) ]
• Apparent Oral Clearance (CL/F) after administration of the CAP formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 1-3) ]
• Apparent Volume of Distribution (Vz/F) after administration of the CAP formulation [ Time Frame: Day 1, Pre-dose, hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 (Period 1-3) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Healthy

Intervention

• Drug: Encorafenib capsule formulation (CAP)
  A single encorafenib dose of the CAP formulation
• Drug: Encorafenib first formulation
  first formulation
• Drug: Encorafenib second formulation
  second formulation
• Drug: Rabeprazole tablet
  Proton-pump inhibitor

Study Arms

• Experimental: Four Period Treatment Sequence: PPI Effect
  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.
  Interventions:

  • Drug: Encorafenib capsule formulation (CAP)
  • Drug: Encorafenib first formulation
  • Drug: Encorafenib second formulation
  • Drug: Rabeprazole tablet
• Experimental: Four Period Treatment Sequence: PPI Effect Second Formulation
  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.
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 1, 2022): 18
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: September 30, 2022
• Actual Primary Completion Date: September 30, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05446142
• Other Study ID Numbers: C4221024
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current

Collaborators

• Ono Pharmaceutical Co. Ltd
• Pierre Fabre Laboratories

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: July 2023