A study to assess the distribution of entrectinib capsule in the blood of healthy adults compared to nasogastric and oral suspension of entrectinib

INTERVENTION:

The study will consist of two parts where participants will be randomly assigned to receive the study treatments in a cross‐over manner. Part 1: The treatments administered to participants in Part 1 of the study will be as follows: Treatment A: Nasogastric administration of 600 mg entrectinib, delivered as a suspension in water on Day 1 following an 8‐hour fast Treatment B: Oral administration of 600 mg entrectinib delivered as a suspension in milk on Day 1 following an 8‐hour fast Treatment C: Oral administration of 600 mg entrectinib capsules on Day 1 following an 8‐hour fast. Part 1 – Sequence

ABC:

Participants will receive three treatments in sequence ABC on Day 1 of Periods 1, 2, and 3 respectively. There will be a 14‐day washout period between each treatment period. Participants will be monitored up to Day 14 after the last dose of the study drug. Part 1 – Sequence

BCA:

Participants will receive three treatments in sequence BCA on Day 1 of Periods 1, 2, and 3 respectively. There will be a 14‐day washout period between each treatment period. Participants will be monitored up to Day 14 after the last dose of the study drug. Part 1 ‐ Sequence

CAB:

Participants will receive treatments in sequence CAB on Day 1 of Periods 1, 2, and 3 respectively. There will be a 14‐day washout period between each treatment period. Participants will be monitored up to Day 14 after the last dose of the study drug. Part 2: The treatments administered to participants in Part 2 of the study will be as follows: Treatment C: Oral administration of 600 mg entrectinib capsules on Day 1 following an 8‐hour fast Treatment D: Oral administration of 600 mg entrectinib delivered as a suspension in water on Day 1 following an 8‐hour fast Treatment E: Oral administration of 30 mg lansoprazol

CONDITION:

Bioavailability of entrectinib in healthy participants ; Not Applicable

PRIMARY OUTCOME:

1. Maximum observed plasma concentration (Cmax) of entrectinib and M5 (its metabolite) measured from blood samples collected at pre‐dose and multiple timepoints up to 96 hours post entrectinib administration in each of the three periods (1, 2 and 3) in both Part 1 and Part 2; 2. Area under the plasma concentration versus time curve from time zero extrapolated to infinity (AUC0‐inf) of entrectinib and M5 (its metabolite) measured from blood samples collected at pre‐dose and multiple timepoints up to 96 hours post entrectinib administration in each of the three periods (1, 2 and 3) in both Part 1 and Part 2

SECONDARY OUTCOME:

1. Time to maximum observed plasma concentration (Tmax) of entrectinib and its metabolite, M5 (as appropriate) measured from blood samples collected at pre‐dose and multiple timepoints up to 96 hours post entrectinib administration in each of the three periods (1, 2 and 3) in both Part 1 and Part 2; 2. Area under the plasma concentration versus time curve from hour zero to the last measurable concentration (AUC0‐t) of entrectinib and its metabolite, M5 (as appropriate) measured from blood samples collected at pre‐dose and multiple timepoints up to 96 hours post entrectinib administration in each of the three periods (1, 2 and 3) in both Part 1 and Part 2 ; 3. Apparent terminal elimination half‐life (t1/2) of entrectinib and its metabolite, M5 (as appropriate) measured from blood samples collected at pre‐dose and multiple timepoints up to 96 hours post entrectinib administration in each of the three periods (1, 2 and 3) in both Part 1 and Part 2; 4. Relative bioavailability for AUCinf (Frel) of entrectinib and its metabolite, M5 (as appropriate) measured from blood samples collected at pre‐dose and multiple timepoints up to 96 hours post entrectinib administration in each of the three periods (1, 2 and 3) in both Part 1 and Part 2; 5. Metabolite (M5) to parent (entrectinib) ratio for AUCinf (MPR) measured from blood samples collected at pre‐dose and multiple timepoints up to 96 hours post entrectinib administration in each of the three periods (1, 2 and 3) in both Part 1 and Part 2; 6. Percentage of participants with adverse events (AEs) and severity of AEs determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) collected from screening up to 14 days after the final dose of entrectinib (up to approximately 70 days)

INCLUSION CRITERIA:

1. Female of non‐childbearing potential or male, between 18 and 55 years of age, inclusive, at Screening 2. Within body mass inde X(BMI) range of 18.0 to 32.0 kg/m², inclusive, and weighing at least 50 kg at Screening 3. Healthy in the opinion of the investigator. Healthy is defined by the absence of evidence of any active disease or clinically significant medical condition based on a detailed medical history, physical examination, vital signs and 12‐lead ECG assessment, and clinical laboratory evaluation results 4. Negative hepatitis panel (hepatitis B surface antigen and hepatitis C virus antibody) and negative human immunodeficiency virus (HIV) antibody screens 5. Females must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at each Check‐in (Day ‐1)