A Study to Compare the Relative Bioavailability of Brigatinib When Swallowed as a Solution Versus When Swallowed as a Tablet in Healthy Adults

Study Overview
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Brief Summary
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The main aim of this study is to compare the amount of brigatinib in the blood of healthy adults after they have swallowed one dose either as a solution or as a tablet.

Detailed Description
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The drug being tested in this study is called brigatinib. Brigatinib is being tested to assess its relative bioavailability when administered as an oral solution versus as an immediate-release tablet in healthy participants. The study will enroll approximately 12 participants. Participants will be randomly assigned to one of the treatment sequences: Sequence 1: Treatment A followed by Treatment B Sequence 2: Treatment B followed by Treatment A wherein Treatment A is a 90 mg oral solution dose and Treatment B is a 90 mg tablet dose. There will be a washout period of at least 14 days between brigatinib administration in each study period. The follow-up contact will occur 14 (±2) days post the last dose of study drug. This single-center trial will be conducted in the United States. The overall study duration is approximately 56 days.

Official Title
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A Phase 1, Open-Label, Randomized, Single-Dose, 2-Period, Crossover Study to Evaluate the Relative Bioavailability of Brigatinib Administered as an Oral Solution Versus an Immediate-Release Tablet in Adult Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Brigatinib
* Drug: Brigatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Continuous nonsmoker who has not used nicotine-containing products for at least 3 months prior to the first dosing and throughout the study. Body mass index (BMI) ≥18.0 and ˂32.0 kilograms per meters squared (kg/m2) at screening. Pulse rate between 60 and 100 beats per minute (bpm) and a blood pressure between 90 to 140 millimeters of mercury (mmHg) systolic and 40 to 90 mmHg diastolic at screening and prior to dosing of Period 1. Creatine phosphokinase is ≤1.1x upper limit of normal [ULN]; lipase, amylase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, glucose, and activated partial thromboplastin time (aPTT) are ≤ULN at screening and check-in of Period 1. Exclusion Criteria: Any history of major surgery. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds. Unable to refrain from or anticipates the use of any drug, including prescription and nonprescription medications, herbal remedies, or vitamin supplements within 28 days prior to the first dosing and throughout the study. Positive results at screening for Human Immunodeficiency Virus (HIV), Hepatitis B surface Antigen (HBsAg), or Hepatitis C Virus (HCV). Positive coronavirus disease 2019 (COVID-19) results at first check-in. Donation of blood or significant blood loss within 56 days prior to the first dosing. Plasma donation within 7 days prior to the first dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A followed by Treatment B<br>Participants will receive 90 mg oral solution of brigatinib in a fasted state on Day 1 of Period 1 (Treatment A) followed by a washout period of at least 14 days and will receive 90 mg tablet of brigatinib in a fasted state on Day 1 of Period 2 (Treatment B). | Drug: Brigatinib<br>* Brigatinib oral solution<br>Drug: Brigatinib<br>* Brigatinib tablet<br>* Other names: ALUNBRIG®;|
| Experimental: Treatment B followed by Treatment A<br>Participants will receive 90 mg tablet of brigatinib in a fasted state on Day 1 of Period 1 (Treatment B) followed by a washout period of at least 14 days and will receive 90 mg oral solution of brigatinib in a fasted state on Day 1 of Period 2 (Treatment A). | Drug: Brigatinib<br>* Brigatinib oral solution<br>Drug: Brigatinib<br>* Brigatinib tablet<br>* Other names: ALUNBRIG®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax: Maximum Observed Plasma Concentration for Brigatinib |  | Predose at Day 1 and multiple times (up to 168 hours) post dose up to Day 8 of Period 1 and Period 2 (Each Period length= 8 days) | 
| AUClast: Area Under the Plasma Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Brigatinib |  | Predose at Day 1 and multiple times (up to 168 hours) post dose up to Day 8 of Period 1 and Period 2 (Each Period length= 8 days) | 
| AUC∞: Area Under the Plasma Concentration-Time Curve from Time 0 to Infinity for Brigatinib |  | Predose at Day 1 and multiple times (up to 168 hours) post dose up to Day 8 of Period 1 and Period 2 (Each Period length= 8 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent form (ICF) to participate in a study. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a study intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the study intervention or medicinal product. An SAE is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or is an important medical event. | From signing of informed consent to 14 (±2) days after last dose (up to 56 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy