Determination of the Relative Bioavailability of ARQ 197 Tablet Formulation With Capsule C Formulation as a Reference in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1, randomized, open label, 2 treatment, 2 period, 2-way crossover study, with an extension phase design in which the steady state PK of ARQ 197 will be investigated using the tablet administered in fed state (test treatment) and capsule administered at least 1 hour before or 2 hours after a meal (reference treatment) in subjects with advanced solid tumors.

Official Title
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An Open-Label, Phase 1, Randomized, Two-Treatment, Two-Period, Two-Way Crossover, Relative Bioavailability Study Of A Capsule And A Tablet Formulation Of ARQ 197 In Subjects With Advanced Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Tivantinib (ARQ 197) Capsule
* Drug: Tivantinib (ARQ 197) Tablet
* Drug: Tivantinib (ARQ 197) Capsule D, oral


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a histologically or cytologically confirmed advanced solid tumor at screening. Male or female equal or greater than 18 years of age. All female subjects of childbearing potential must each have a negative serum pregnancy test result before initiating study treatment. An Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 2 Adequate bone marrow, liver, and renal function, defined as: Platelet count equal or greater than 75 x 10(9)/L Hemoglobin (Hb) equal or greater than 9.0 g/dL Absolute neutrophil count (ANC) equal or greater than 1.5 x 10(9)/L Total bilirubin equal or less than 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) equal or less than 3 x ULN (equal or less than 5 x ULN for subjects with liver metastases) Serum creatinine equal or less than 1.5 x ULN Exclusion Criteria: History of cardiac disease: Active coronary artery disease (CAD), defined as myocardial infarction (MI), unstable angina, coronary bypass graft (CABG), or stenting within 6 months prior to study entry (an MI that occurred > 6 months prior to study entry is permitted) Evidence of uncontrolled bradycardia or other cardiac arrhythmia defined as equal or greater than Grade 2 according to NCI CTCAE, version 4.0, or uncontrolled hypertension Active, clinically serious infection(s) defined as equal or greater than Grade 2 according to NCI CTCAE, version 4.0. Known metastatic brain or meningeal tumors, unless the subject is > 3 months from definitive therapy and clinically stable (supportive therapy with steroids or anticonvulsant medications is allowed) with respect to the tumor at the time of first dose of study drug. Prior therapy with mesenchymal-epithelial transition factor (c-MET) inhibitors, including ARQ 197.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARQ 197 Capsule, oral<br>Oral BID 360 mg dose (Capsule C: 6 X 60 mg) of ARQ 197 at least 1 hour before or 2 hours after a meal for 7 days | Drug: Tivantinib (ARQ 197) Capsule<br>* Oral BID 360 mg dose (Capsule C: 6 X 60 mg) of ARQ 197 at least 1 hour before or 2 hours after a meal for 7 days<br>* Other names: Tivantinib;|
| Experimental: ARQ 197 Tablet, oral<br>Oral BID 360 mg dose (Tablet: 3 x 120 mg) of ARQ 197 under fed conditions for 7 days | Drug: Tivantinib (ARQ 197) Tablet<br>* Oral BID 360 mg dose (Tablet: 3 x 120 mg) of ARQ 197 under fed conditions for 7 days<br>* Other names: Tivantinib;|
| Experimental: ARQ 197 Capsule D, oral<br>Oral BID 360 mg dose (Capsule D: 3 x 120 mg) of ARQ 197 under fed conditions in the extension phase | Drug: Tivantinib (ARQ 197) Capsule D, oral<br>* Oral BID 360 mg dose (Capsule D: 3 x 120 mg) of ARQ 197 under fed conditions in the extension phase<br>* Other names: Tivantinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the relative bioavailability of ARQ 197 tablet formulation with capsule C formulation | The primary endpoints are the area under the concentration time curve from time of dosing until 12 hours post-dose (AUC0-12) and maximum observed concentration in plasma (Cmax) of ARQ 197 following the administration of the tablet (fed conditions) and capsule formulation (at least 1 hour before or 2 hours after a meal). | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of additional pharmacokinetic parameters of ARQ 197 tablet formulation and capsule C formulation | Time until Cmax (tmax), apparent oral clearance (CL/F), and apparent volume of distribution (V/F) of ARQ 197, and if possible, minimum observed concentration (Cmin) and average observed concentration (Cavg) following the administration of the tablet (fed conditions) and capsule formulation (at least 1 hour before or 2 hours after a meal) | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relative bioavailability, ARQ 197