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A Study to Assess the Effect of Ketoconazole on the Metabolism of ABT-199

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ClinicalTrials.gov Identifier: NCT01969669
Recruitment Status : Completed
First Posted : October 25, 2013
Last Update Posted : November 20, 2017
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

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
Non-Hodgkin's Lymphoma Drug: ABT-199 Drug: Ketoconazole 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase 1 Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of ABT-199
Study Start Date : December 2013
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

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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 Name: GDC-0199

Drug: Ketoconazole
Subjects will be dosed with ABT-199, then dosed with ABT-199 in combination with ketoconazole




Primary Outcome Measures :
  1. 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 [ Time Frame: 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 :
  1. Number of subjects with adverse events [ Time Frame: 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

  2. Percentage of subjects with adverse events [ Time Frame: 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

  3. Change in physical exam finding, including vital signs [ Time Frame: Measured from Day 1 up to 30 days after the last dose of study drug ]
    Body temperature, weight, blood pressure, heart rate

  4. Change in clinical laboratory test results [ Time Frame: Measured from Day 1 up to 30 days after the last dose of study drug ]
    Chemistry, coagulation, hematology, urinalysis

  5. Change in cardiac assessment findings [ Time Frame: Measured from Day 1 up to Day 12 ]
    Electrocardiogram



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01969669


Locations
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United States, Arizona
Site Reference ID/Investigator# 97498
Tucson, Arizona, United States, 85724-5024
United States, New Hampshire
Site Reference ID/Investigator# 92593
Lebanon, New Hampshire, United States, 03756-0001
United States, New Jersey
Site Reference ID/Investigator# 101415
Hackensack, New Jersey, United States, 07601
Sponsors and Collaborators
AbbVie
Genentech, Inc.
Investigators
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Study Director: David Chien, MD AbbVie

Publications of Results:
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT01969669     History of Changes
Other Study ID Numbers: M13-364
First Posted: October 25, 2013    Key Record Dates
Last Update Posted: November 20, 2017
Last Verified: October 2014

Keywords provided by AbbVie:
non-Hodgkin's lymphoma
GDC-0199
Safety
Relapsed
Refractory
ABT-199
Pharmacokinetics
Cancer

Additional relevant MeSH terms:
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Venetoclax
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Ketoconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Antineoplastic Agents