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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT01401933
First received: April 29, 2011
Last updated: October 31, 2011
Last verified: October 2011
  Purpose

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


Condition Intervention Phase
Advanced Solid Tumors
Drug: Linifanib
Drug: Rifampin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase 1 Study To Assess the Effect of Rifampin on the Pharmacokinetics of Linifanib in Subjects With Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • To investigate the effect of rifampin on the pharmacokinetic of linifanib in subjects with advanced or metastatic solid tumors. [ Time Frame: Blood samples for the PK of linifanib will be collected at various time points from Day 1 through Day 17. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Safety: Adverse Events - The number of participants with adverse events will be reported as a measure of Safety. [ Time Frame: Through out the study ] [ Designated as safety issue: Yes ]
    The investigators will monitor each subject for clinical and lab evidence of adverse events on a routine basis 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. [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
    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.

  • Safety: Clinical Lab Tests will be performed for each participant as a safety measure. [ Time Frame: Screening, Day 1, Day 13, Day 17/Final Visit and 30 day safety follow up visit. ] [ Designated as safety issue: Yes ]
    Chemistry, hematology, urinalysis lab tests.


Enrollment: 14
Study Start Date: May 2011
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Linifanib Drug: Linifanib
QD on Days 1 and 13
Other Name: ABT-869
Drug: Rifampin
QD on Days 5-16
Other Name: Rifadin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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..
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01401933

Locations
United States, Arizona
Site Reference ID/Investigator# 49953
Tucson, Arizona, United States, 85724-5024
United States, Wisconsin
Site Reference ID/Investigator# 49952
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Abbott
Investigators
Study Director: Mark D. McKee, MD Abbott
  More Information

No publications provided

Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT01401933     History of Changes
Other Study ID Numbers: M11-307
Study First Received: April 29, 2011
Last Updated: October 31, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Rifampin
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antitubercular
Antitubercular Agents
Enzyme Inhibitors
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014