A Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of Linifanib (ABT-869)

NCT01114191 | Completed Phase 1

• 1 other identifier: M11-306
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase 1, open-label study designed to determine the interaction of ketoconazole with ABT-869.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• To investigate the effect of ketoconazole on the pharmacokinetics of ABT-869 in subjects with advanced or metastatic solid tumors.

  Blood samples for the PK of ABT-869 and ketoconazole will be collected at designated time points throughout the study.

  Different timepoints on Days 1-12

Secondary Outcomes (1)

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

  Throughout the study

Study Arms (1)

Arm 1

EXPERIMENTAL

Drug: ABT-869; Drug: ketoconazole

Interventions

ABT-869 DRUG

2.5mg \[5 mg days 1, 8 and 12. 17.5 mg on days 13 and after\]

Also known as: linifanib, ABT-869

Arm 1

ketoconazole DRUG

400 mg days 6-11

Arm 1

Eligibility Criteria

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

You may qualify if:

• Male or female and age is \>= 18 years.
• Must have a histologically or cytologically confirmed non-hematologic malignancy.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
• Must have adequate bone marrow, renal and hepatic function as follows:
• Bone Marrow: Absolute neutrophil count (ANC) \>= 1,500/mm3; Platelets \>= 100,000/mm3 ; Hemoglobin \>= 9.0 g/dL
• Renal function: serum creatinine \<= 2.0 mg/dL;
• 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
• Must have PTT \<= 1.5 x ULN and/or INR \<= 1.5.
• Women of childbearing potential and men must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and up to 90 days following completion of therapy. Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to initiation of treatment and/or post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Total abstinence from sexual intercourse (minimum one complete menstrual cycle);
• Vasectomized male subjects or vasectomized partner of female subjects;
• Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration; if the subject is currently using a hormonal contraceptive, she should also use a barrier method during this study and for 1 month after study completion;
• Intrauterine device (IUD);
• Double barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or creams);
• Additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 90 days following completion of therapy.

You may not qualify if:

• 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.
• Has undergone major surgery within 21 days of Study Day 1.
• 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).
• Has a central thoracic tumor lesion as defined by location involving or abutting the hilar structures. The presence of central nodal disease is allowed.
• Female subjects who are pregnant or breastfeeding.
• Has received potential inhibitors of the metabolism of linifanib within 21 days prior to initial study drug administration. Such drugs include CYP3A inhibitors e.g., triazole, itraconazole, ketoconazole, fluconazole, grapefruit juice, verapamil, diltiazem, aprepitant, clarithromycin and erythromycin; CYP1A2 inhibitors e.g., fluvoxamine, ciprofloxacin, mexiletine, propafenone and zileuton; CYP2C19 inhibitors e.g., omeprazole; CYP2C8 substrates e.g., repaglinide, paclitaxel and rosiglitazone and CYP3A inducers e.g., rifampin and carbamazepine.
• Has proteinuria defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade \> 1 at baseline as measured by a urine dipstick (2+ or greater) and confirmed by a 24 hour urine collection (\> 1 g/24 hrs). Subjects may be re-screened if proteinuria is shown to be controlled with or without intervention.
• Currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure (BP) \> 100 mmHg; or systolic blood pressure (BP) \> 150 mmHg. Subjects may be re-screened if BP is shown to be controlled with or without intervention.
• Clinically significant uncontrolled condition(s) including but not limited to:
• Active uncontrolled infection
• Class III or IV heart failure as defined by the New York Heart Association functional classification system
• Unstable angina pectoris or cardiac arrhythmia
• Myocardial infarction within last 6 months
• History of adrenal insufficiency
• History of cerebral vascular accident within last 6 months

Sponsors & Collaborators

• Abbott: lead

Study Sites (2)

Site Reference ID/Investigator# 35784

Detroit, Michigan, 48201, United States

Location

Site Reference ID/Investigator# 36527

Lebanon, New Hampshire, 03756-0001, United States

Location

MeSH Terms

Interventions

linifanib; Ketoconazole

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic 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: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 29, 2010
• First Posted: May 3, 2010
• Study Start: May 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: July 26, 2011

Record last verified: 2011-07

Locations

US (2)