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

NCT01401933 | Completed Phase 1

• 1 other identifier: M11-307
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Safety: Adverse Events - The number of participants with adverse events will be reported as a measure of Safety.

  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.

  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.

  Screening, Day 1, Day 13, Day 17/Final Visit and 30 day safety follow up visit.

Study Arms (1)

Linifanib

EXPERIMENTAL

Drug: Linifanib; Drug: Rifampin

Interventions

Linifanib DRUG

QD on Days 1 and 13

Also known as: ABT-869

Linifanib

Rifampin DRUG

QD on Days 5-16

Also known as: Rifadin

Linifanib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age is greater than or equal to 18 years.
• Subject must have a histologically or cytologically confirmed non-hematologic malignancy other than HCC.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
• 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).
• Subject must have Partial Thromboplastin Time (PTT) \</= 1.5 X Upper Limit of Normal ( ULN) and International Normalized Ratio (INR) \</= 1.5.

You may not qualify if:

• 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.
• Subject has undergone major surgery within 21 days of Study Day 1.
• 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).
• 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.
• Current enrollment in another clinical trial..

Sponsors & Collaborators

• Abbott: lead

Study Sites (2)

Site Reference ID/Investigator# 49953

Tucson, Arizona, 85724-5024, United States

Location

Site Reference ID/Investigator# 49952

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

linifanib; Rifampin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Mark D. McKee, MD

  Abbott

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2011
• First Posted: July 26, 2011
• Study Start: May 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: November 2, 2011

Record last verified: 2011-10

Locations

US (2)