A Performance and Bioavailability Study of Entrectinib in Healthy Volunteers.
Condition: Solid Tumor
Intervention: Entrectinib 600 mg (T1); Entrectinib 600 mg (T2); Entrectinib 200 mg (R); Entrectinib 200 mg (T)
Intervention description: Test formulation 1 (T1): Multi-particulate formulation 1: entrectinib film-coated mini-tablets; Test formulation 2 (T2): Multi-particulate formulation 2: entrectinib film-coated mini-tablets; Reference formulation (R): entrectinib hard capsules; Test formulation (T): entrectinib HPMC capsules
Intervention MeSH terms: Entrectinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study will evaluate the bioavailability, palatability, safety and tolerability of
      entrectinib in healthy volunteers. Part 1 of the study will explore the performance of
      entrectinib multi-particle formulation. Part 2 will evaluate the effect of drug substance
      particle size on entrectinib bioavailability.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A body mass index (BMI) between 18.0 and 32.0 kilogram per square meter (kg/m2),
             inclusive, and weighing >/=50 kg.

          -  Agreement to comply with measures to prevent pregnancy and restrictions on egg and
             sperm donation

        Exclusion Criteria:

          -  Women of childbearing potential, women who are pregnant or breastfeeding, or intending
             to become pregnant during the study or within 14 days after the final dose of
             entrectinib or have a pregnant partner

          -  A clinical significant medical history of gastrointestinal surgery (e.g., gastric
             bypass) or other gastrointestinal disorder (e.g., malabsorption syndrome) that might
             affect absorption of medicines from the gastrointestinal tract

          -  Presence of a clinically significant disease, illness, medical condition or disorder,
             or any other medical history determined by the investigator to be clinically
             significant and relevant

          -  Clinically significant change in health status, or any major illness, or clinically
             significant acute infection or febrile illness

          -  Use of moderate or potent inhibitors or inducers of CYP P450 3A4 enzyme or P-gp
             transporter, or use of other prohibited medications

          -  Participation in any other clinical study involving an investigational medicinal
             product (IMP) or device

          -  A positive test result for hepatitis B, hepatitis C (HCV), or human immunodeficiency
             virus (HIV)

          -  Current smokers and those who have smoked, or users of e-cigarettes and nicotine
             replacement products within the last 12 months

          -  Known history of clinically significant hypersensitivity, or severe allergic reaction,
             to entrectinib or related compounds