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

Daiichi Sankyo

Status and phase: Completed; Phase 1

Conditions: Solid Tumors

Treatments: Drug: Tivantinib (ARQ 197) Tablet; Drug: Tivantinib (ARQ 197) Capsule D, oral; Drug: Tivantinib (ARQ 197) Capsule

Study type: Interventional

Funder types: Industry

Identifiers

NCT01149720

ARQ197-A-U157

Details and patient eligibility

About

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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

ARQ 197 Capsule, oral

Experimental group

Description:

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

Treatment:

Drug: Tivantinib (ARQ 197) Capsule

ARQ 197 Tablet, oral

Experimental group

Description:

Oral BID 360 mg dose (Tablet: 3 x 120 mg) of ARQ 197 under fed conditions for 7 days

Treatment:

Drug: Tivantinib (ARQ 197) Tablet

ARQ 197 Capsule D, oral

Experimental group

Description:

Oral BID 360 mg dose (Capsule D: 3 x 120 mg) of ARQ 197 under fed conditions in the extension phase

Treatment:

Drug: Tivantinib (ARQ 197) Capsule D, oral