A Relative Bioavailability Study Evaluating Two New Encorafenib Formulations

NCT05446142 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C4221024
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Encorafenib; Rabeprazole; Healthy adult participants

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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 (8)

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

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

• Terminal Half-Life (t½) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole

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

• Apparent Clearance (CL/F) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole

  0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose

• Apparent Volume of Distribution (Vz/F) Following Single Oral Doses of Encorafenib 75 mg Alone and With Rabeprazole

  0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 48 hours postdose

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Baseline up to Day 28 after the last encorafenib dose (the total duration of the study was approximately 60 days from baseline)

Study Arms (2)

Four Period Treatment Sequence: PPI Effect

EXPERIMENTAL

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.

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

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.

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

Interventions

Encorafenib capsule formulation (CAP) DRUG

A single encorafenib dose of the CAP formulation

Four Period Treatment Sequence: PPI Effect; Four Period Treatment Sequence: PPI Effect Second Formulation

Encorafenib first formulation DRUG

first formulation

Four Period Treatment Sequence: PPI Effect; Four Period Treatment Sequence: PPI Effect Second Formulation

Encorafenib second formulation DRUG

second formulation

Four Period Treatment Sequence: PPI Effect; Four Period Treatment Sequence: PPI Effect Second Formulation

Rabeprazole tablet DRUG

Proton-pump inhibitor

Four Period Treatment Sequence: PPI Effect; Four Period Treatment Sequence: PPI Effect Second Formulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead
• Ono Pharmaceutical Co. Ltd: collaborator
• Pierre Fabre Laboratories: collaborator

Study Sites (1)

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

encorafenib; Dosage Forms; Rabeprazole

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2022
• First Posted: July 6, 2022
• Study Start: July 1, 2022
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: February 23, 2024
• Results First Posted: February 23, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)