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

Registration Number
NCT01149720
Lead Sponsor
Daiichi Sankyo
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
ARQ 197 Tablet, oralTivantinib (ARQ 197) TabletOral BID 360 mg dose (Tablet: 3 x 120 mg) of ARQ 197 under fed conditions for 7 days
ARQ 197 Capsule D, oralTivantinib (ARQ 197) Capsule D, oralOral BID 360 mg dose (Capsule D: 3 x 120 mg) of ARQ 197 under fed conditions in the extension phase
ARQ 197 Capsule, oralTivantinib (ARQ 197) CapsuleOral 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
Primary Outcome Measures
NameTimeMethod
Determination of the relative bioavailability of ARQ 197 tablet formulation with capsule C formulation14 days

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).

Secondary Outcome Measures
NameTimeMethod
Assessment of additional pharmacokinetic parameters of ARQ 197 tablet formulation and capsule C formulation14 days

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)

Trial Locations

Locations (4)

Florida Cancer Specialists

🇺🇸

Fort Myers, Florida, United States

Premiere Oncology

🇺🇸

Santa Monica, California, United States

Sarah Cannon Research Institute (SCRI)

🇺🇸

Nashville, Tennessee, United States

START - South Texas Accelerated Research Therapeutics, LLC

🇺🇸

San Antonio, Texas, United States

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