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

NCT ID: NCT01969669

Last Updated: 2017-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-31

Study Completion Date

2014-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non-Hodgkin's Lymphoma

Keywords

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non-Hodgkin's lymphoma GDC-0199 Safety Relapsed Refractory ABT-199 Pharmacokinetics Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Arm A (ABT-199 and ketoconazole)

Group Type EXPERIMENTAL

ABT-199

Intervention Type DRUG

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

Ketoconazole

Intervention Type DRUG

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

Interventions

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ABT-199

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

Intervention Type DRUG

Ketoconazole

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

Intervention Type DRUG

Other Intervention Names

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GDC-0199

Eligibility Criteria

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Inclusion Criteria

* Subject must have relapsed or refractory non-Hodgkin's lymphoma.

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.


* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Chien, MD

Role: STUDY_DIRECTOR

AbbVie

Locations

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Site Reference ID/Investigator# 97498

Tucson, Arizona, United States

Site Status

Site Reference ID/Investigator# 92593

Lebanon, New Hampshire, United States

Site Status

Site Reference ID/Investigator# 101415

Hackensack, New Jersey, United States

Site Status

Countries

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United States

References

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Agarwal SK, Salem AH, Danilov AV, Hu B, Puvvada S, Gutierrez M, Chien D, Lewis LD, Wong SL. Effect of ketoconazole, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax, a BCL-2 inhibitor, in patients with non-Hodgkin lymphoma. Br J Clin Pharmacol. 2017 Apr;83(4):846-854. doi: 10.1111/bcp.13175. Epub 2017 Jan 18.

Reference Type RESULT
PMID: 27859472 (View on PubMed)

Other Identifiers

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M13-364

Identifier Type: -

Identifier Source: org_study_id