A Study Evaluating the Bioavailability of Two Formulations of Linifanib and Food Effect on Pharmacokinetics of Linifanib in Subjects With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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A pharmacokinetic study to compare 2 clinical formulations of linifanib and the effect of food on the pharmacokinetics of linifanib.

Detailed Description
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This study is designed to evaluate the bioavailability of linifanib from two formulations and the effect of food on the pharmacokinetics of the linifanib formulation intended for commercialization. Subjects may enroll in a separate extension study to continue receiving linifanib after completion of this study.

Official Title
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A Phase 1, Open Label, Randomized, Adaptive, Cross-Over Study Evaluating the Bioavailability of Two Formulations of Linifanib and Food Effect on Pharmacokinetics of Linifanib in Subjects With Advanced or Metastatic Solid Tumors

Conditions
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Advanced or Metastatic Solid Tumors

Intervention / Treatment
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* Drug: linifanib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age is greater than or equal to 18 years. Subject must have a histologically or cytologically confirmed non-hematologic malignancy other than Hepatocellular Carcinoma (HCC). Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2. Subject must have adequate bone marrow, renal and hepatic function as follows: Bone Marrow: Absolute neutrophil count (ANC) >= 1,500/mm3 (1.5 X 109/L); Platelets >= 75,000/mm3 (75 X 109/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. Exclusion Criteria 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 Period 1, 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, Period 1). Current enrollment in another clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: linifanib<br>Single Doses | Drug: linifanib<br>* Single Dose on Day 1 of Periods 1, 2 and 3 (Bioavailability Portion) Single Dose on Day 1 of Periods 1 and 2 (Food Effect Portion)<br>* Other names: ABT-869;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calculate the Cmax and Tmax of participating subjects |  | PK parameters will be measured: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose in each study period. | 

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 on Days 1 through 7 of Periods 1, 2 and 3. The investigators will question each subject regarding any adverse effects that they have experienced and record any events on the case report forms. All adverse events will be followed to a satisfactory clinical resolution. | All adverse events occuring from Day 1 of Period 1 through the Final Visit will be reported. | 
| 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 at Screening, Day 1 of Periods 1, 2 and 3 and Day 5, Period 2 (FE portion), Day 5, Period 3 (BA Portion)/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, Periods 1 and 2, Day 5, Period 2 (FE portion), Day 5, Period 3 (BA portion)/Final Visit and 30 day safety follow-up. |