Effect of Rifampin on the Pharmacokinetics of Linifanib in Subjects With Advanced or Metastatic Solid Tumors

A Phase 1 Study To Assess the Effect of Rifampin on the Pharmacokinetics of Linifanib in Subjects With Advanced or Metastatic Solid Tumors

This is a phase 1, open-label study designed to determine the interaction of rifampin with linifanib.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Linifanib; Drug: Rifampin

Detailed Description

This study is designed to explore the drug interaction between rifampin and linifanib to determine the potential effect of rifampin on the metabolism of linifanib. Linifanib will be taken alone or in combination with rifampin. The safety of a single dose administration of linifanib when administered alone and in combination with rifampin will be assessed. Subjects may enroll in a separate extension study to continue receiving linifanib after completion of this study.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • Site Reference ID/Investigator# 49953
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Site Reference ID/Investigator# 49952

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Age is greater than or equal to 18 years.
2. Subject must have a histologically or cytologically confirmed non-hematologic malignancy other than HCC.
3. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.

4. Subject must have adequate bone marrow, renal and hepatic function.

   • Bone Marrow: Absolute neutrophil count (ANC) >= 1,500/mm^3 (1.5 X 10^9/L); Platelets >= 75,000/mm^3 (75 X 10^9/L); Hemoglobin >= 9.0 g/dL (1.4 mmol/L)
   • Renal function: serum creatinine <= 2.0 mg/dL (0.81 mmol/L);
   • Hepatic function: AST and ALT <= 1.5 X ULN unless liver metastases are present, then AST and ALT <= 5.0 X ULN; bilirubin <= 1.5 mg/dL (0.026 mmol/L).
5. Subject must have Partial Thromboplastin Time (PTT) </= 1.5 X Upper Limit of Normal ( ULN) and International Normalized Ratio (INR) </= 1.5.

Exclusion Criteria

1. Subject has received anti-cancer therapy including investigational agents, cytotoxic chemotherapy, radiation therapy or biologic therapy within 21 days or within a period defined by 5 half lives, whichever is shorter, prior to study drug administration. In addition subject has not recovered to less than or equal to Grade 1 clinically significant adverse effects/toxicities of the previous therapy.
2. Subject has undergone major surgery within 21 days of Study Day 1.
3. Subject has untreated brain or meningeal metastases. Subjects with treated brain metastases that are radiographically or clinically stable (for at least 4 weeks after therapy) and who have no evidence of cavitation or hemorrhage in the brain lesion, are eligible provided that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to Study Day 1).
4. Subject has received potential inhibitors of the metabolism of linifanib within 21 days prior to initial study drug administration. Such drugs include CYP3A inhibitors, CYP1A2 inhibitors, CYP2C19 inhibitors, CYP2C8 substrates and CYP3A inducers.
5. Current enrollment in another clinical trial..

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Linifanib	Drug: Linifanib; QD on Days 1 and 13; Other Names: ABT-869; Drug: Rifampin; QD on Days 5-16; Other Names: Rifadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the effect of rifampin on the pharmacokinetic of linifanib in subjects with advanced or metastatic solid tumors.	To assess the effect of rifampin on the pharmacokinetics of linifanib and metabolite(s), an analysis will be performed for the natural logarithms of Cmax and AUC of linifanib and metabolite(s) with concentrations that permit confident determination of values of the pharmacokinetic variables. A paired t-test will be performed to compare the central value on Study Day 13 (with rifampin) to that on Study Day 1 (without rifampin). Point estimates and 90% confidence intervals will also be provided.	Blood samples for the PK of linifanib will be collected at various time points from Day 1 through Day 17.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Adverse Events - The number of participants with adverse events will be reported as a measure of Safety.	The investigators will monitor each subject for clinical and lab evidence of adverse events on a routine basis through out the study.	Through out the study
Safety: Physical Examination and Vital Signs - Physical examination will be performed and vital signs will be assessed for participants as a measure of safety.	Complete physical exam, including body weight, will be done at Screening and Day 1. A symptom-directed physical exam, including weight, will be done at Day 13, Day 17/Final Visit and 30 day safety follow-up.	Physical exam will be done at Screening, Day1, Day 13, Day 17/Final Visit and 30 day safety follow-up. Vital Signs (blood pressure, heart rate, body temperature) will be done at all visits.
Safety: Clinical Lab Tests will be performed for each participant as a safety measure.	Chemistry, hematology, urinalysis lab tests.	Screening, Day 1, Day 13, Day 17/Final Visit and 30 day safety follow up visit.

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Mark D. McKee, MD, Abbott

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: April 29, 2011
• First Submitted That Met QC Criteria: July 22, 2011
• First Posted (Estimate): July 26, 2011

Study Record Updates

• Last Update Posted (Estimate): November 2, 2011
• Last Update Submitted That Met QC Criteria: October 31, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin
• Other Study ID Numbers: M11-307