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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01401933
• Other study ID #: M11-307
• Status: Completed
• Phase: Phase 1
• First received: April 29, 2011
• Last updated: October 31, 2011
• Start date: May 2011
• Est. completion date: October 2011

Study information

• Verified date: October 2011
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Drug:
• Linifanib
QD on Days 1 and 13
• Rifampin
QD on Days 5-16

Locations

Country	Name	City	State
United States	Site Reference ID/Investigator# 49952	Madison	Wisconsin
United States	Site Reference ID/Investigator# 49953	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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	Yes
Secondary	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.	Yes
Secondary	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.	Yes