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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01149720
• Other study ID #: ARQ197-A-U157
• Status: Completed
• Phase: Phase 1
• Start date: July 2010
• Est. completion date: March 2011

Study information

• Verified date: February 2018
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• Tivantinib (ARQ 197) Capsule
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
• Tivantinib (ARQ 197) Tablet
Oral BID 360 mg dose (Tablet: 3 x 120 mg) of ARQ 197 under fed conditions for 7 days
• Tivantinib (ARQ 197) Capsule D, oral
Oral BID 360 mg dose (Capsule D: 3 x 120 mg) of ARQ 197 under fed conditions in the extension phase

Locations

Country	Name	City	State
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Sarah Cannon Research Institute (SCRI)	Nashville	Tennessee
United States	START - South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	Premiere Oncology	Santa Monica	California

Sponsors (3)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.	ArQule, ICON Clinical Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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