A Study to Assess the Effect of Ketoconazole on the Metabolism of ABT-199
Study Details
Study Description
Brief Summary
This is an open-label multicenter, study to assess the pharmacokinetic interaction of ketoconazole with ABT-199 in up to 12 subjects with relapsed or refractory non-Hodgkin's lymphoma.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Detailed Description
This is a Phase 1 study designed to assess how the body processes the study drug ABT-199 when taken alone and in combination with ketoconazole and to assess the safety of ABT-199 in combination with ketoconazole. Subjects may enroll in a separate extension study to continue receiving ABT-199 after completion of this study.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm A (ABT-199 and ketoconazole)
|
Drug: ABT-199
Subjects will be dosed with ABT-199, then dosed with ABT-199 in combination with ketoconazole
Other Names:
Drug: Ketoconazole
Subjects will be dosed with ABT-199, then dosed with ABT-199 in combination with ketoconazole
|
Outcome Measures
Primary Outcome Measures
- Determination of maximum observed plasma concentration (Cmax), time to Cmax (peak time, Tmax), terminal phase elimination rate constant (beta), terminal phase elimination half-life (t1/2), & area under the plasma concentration-time curve (AUC) of ABT-199 [Measured pre-dose and up to 96 hours post-dose ABT-199]
Blood samples for pharmacokinetic (PK) analysis of ABT-199 will be collected at designated timepoints to assess the PK parameters for ABT-199 alone relative to ABT-199 with ketoconazole
Secondary Outcome Measures
- Number of subjects with adverse events [Measured up to 30 days after the last dose of study drug]
Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study
- Percentage of subjects with adverse events [Measured up to 30 days after the last dose of study drug]
Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study
- Change in physical exam finding, including vital signs [Measured from Day 1 up to 30 days after the last dose of study drug]
Body temperature, weight, blood pressure, heart rate
- Change in clinical laboratory test results [Measured from Day 1 up to 30 days after the last dose of study drug]
Chemistry, coagulation, hematology, urinalysis
- Change in cardiac assessment findings [Measured from Day 1 up to Day 12]
Electrocardiogram
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subject must have relapsed or refractory non-Hodgkin's lymphoma.
-
Subject must have histologically documented diagnosis of non-Hodgkin's lymphoma as defined by a B-cell neoplasm in the World Health Organization (WHO) classification scheme except as noted in the exclusion criteria.
-
Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.
-
Subject must have adequate bone marrow (independent of growth factor support per local laboratory reference range), coagulation, renal and hepatic function:
-
Absolute Neutrophil Count (ANC) greater than or equal to 1000/µL (without growth factor support unless neutropenia is clearly due to underlying disease);
-
Platelets greater than or equal to 75,000/mm3 (unless thrombocytopenia is clearly due to disease-related immune thrombocytopenia or to underlying disease; entry platelet count must be independent of transfusion within 14 days of Screening);
-
Hemoglobin greater than or equal to 9.0 g/dL (unless anemia is clearly due to underlying disease; entry hemoglobin must be independent of transfusion within 14 days of Screening);
-
If cytopenias are present, no evidence of myelodysplastic syndrome or hypoplastic bone marrow;
-
Subject must have activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × the upper normal limit (ULN);
-
Calculated creatinine clearance greater than or equal to 50 mL/min using a 24-hour urine collection for creatinine clearance or per the Cockcroft-Gault equation;
-
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3.0 × ULN of institution's normal range;
-
Bilirubin less than or equal to 1.5 × ULN. Subjects with Gilbert's Syndrome may have a bilirubin greater than 1.5 × ULN per discussion with the AbbVie medical monitor.
Exclusion Criteria:
-
Subject has been diagnosed with Post-Transplant Lymphoproliferative Disease (PTLD), Burkitt's lymphoma, Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or mantle cell lymphoma (MCL).
-
Subject is receiving combination anti-retroviral therapy for HIV (due to potential drug-drug interactions between anti-retroviral medications and ABT-199, as well as anticipated ABT-199 mechanism based lymphopenia that may potentially increase the risk of opportunistic infections).
-
Subject has hypersensitivity to ketoconazole.
-
Subject has a cardiovascular disability status of New York Heart Association Class greater than or equal to 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea or anginal pain.
-
Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease within the past 6 months that in the opinion of the investigator would adversely affect his/her participating in this study.
-
Subject has malabsorption syndrome or other condition which precludes enteral route of administration (e.g., prior surgical resection).
-
Subject has undergone an allogeneic stem cell transplant.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Site Reference ID/Investigator# 97498 | Tucson | Arizona | United States | 85724-5024 |
2 | Site Reference ID/Investigator# 92593 | Lebanon | New Hampshire | United States | 03756-0001 |
3 | Site Reference ID/Investigator# 101415 | Hackensack | New Jersey | United States | 07601 |
Sponsors and Collaborators
- AbbVie
- Genentech, Inc.
Investigators
- Study Director: David Chien, MD, AbbVie
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- M13-364