- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02381080
Interaction Study of Ibrutinib and Cytochrome P450 (CYP) 3A Inhibitors in Participants With B-cell Malignancy
June 23, 2017 updated by: Janssen Research & Development, LLC
A Drug-drug Interaction Study of Ibrutinib With Moderate and Strong CYP3A Inhibitors in Patients With B-cell Malignancy
The purpose of this study is to assess the effect of a moderate Cytochrome P450 (CYP) 3A inhibitor (erythromycin) and a strong CYP3A inhibitor (voriconazole) on the steady-state pharmacokinetics (PK [the study of the way a drug enters and leaves the blood and tissues over time]) of repeated oral doses of ibrutinib in participants with B-cell malignancy (cancer or other progressively enlarging and spreading tumors).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This is an open-label (participants and researchers are aware about the treatment participants are receiving), multi-center (when more than 1 hospital or medical school team work on a medical research study), drug-drug interaction (DDI) study of ibrutinib with the moderate and the strong CYP3A inhibitors (erythromycin and voriconazole respectively) in participants with B-cell malignancies (including Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma [CLL/SLL], Follicular Lymphoma [FL], Marginal Zone Lymphoma [MZL], Waldenstrom's Macroglobulinemia [WM] or Mantle Cell Lymphoma [MCL]).
The study will consist of a Screening Phase (28 days), a Treatment Phase (consisting of six 28-days cycles), and an End-of-Treatment (EoT) Visit (within 30 days after the last dose of study drug).
The study will consist of 2 Parts.
In Part 1, extent of the DDI between ibrutinib at dose level of 140 milligram (mg) and CYP3A inhibitors will be assessed.
After completion of Part 1 of the study, an interim analysis of all available PK and safety data will be conducted and Part 2 will only be performed if the observed drug interaction is less than anticipated based on current information.
In Part 2, safety and PK of ibrutinib at dose level of 560 mg administered with CYP3A inhibitors will be assessed.
Participants who continue to derive clinical benefit from ibrutinib treatment at the end of this study, and who are eligible to continue in the PCI-32765CAN3001 study (NCT01804686) will end their participation in this trial, have an EoT visit completed, and will continue receiving ibrutinib as a part of the PCI-32765CAN3001 protocol.
Participants' safety will be monitored throughout the study.
Study Type
Interventional
Enrollment (Actual)
26
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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N/a N/a, Canada
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Moscow, Russian Federation
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Petrozavodsk, Russian Federation
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St. Petersburg, Russian Federation
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Madrid, Spain
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Pamplona, Spain
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically or cytologically confirmed Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone Lymphoma (MZL), Mantle Cell Lymphoma (MCL), Follicular Lymphoma (FL), or Waldenstrom's Macroglobulinemia (WM)
- Relapsed or refractory disease after at least 1 prior line of systemic therapy (participants with FL or MZL must have failed anti-CD20 monoclonal antibody containing chemotherapy regimen)
- Eastern Cooperative Oncology Group Performance Status score of 0 or 1
- Hematology values within the following limits: a) Absolute neutrophil count (ANC) greater than and equal to (>=) 1.0*10^9 per liter (L); b) Platelets >=50*10^9/L without transfusion support within 7 days; c) Hemoglobin >=8 gram per deciliter (g/dL) without transfusion support within 7 days; d) Prothrombin time /International normalized ratio (PT/INR) less than equal to (<=) 1.5*Upper Limit of Normal (ULN) and activated partial thromboplastin time (aPTT) <=1.5*ULN
- Biochemical values within the following limits: a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3.0*ULN; b) Total bilirubin <=1.5*ULN (unless due to Gilbert's syndrome); c) Serum creatinine <=1.5*ULN or a calculated creatinine clearance of >=50 milliliter per minute per 1.73 square meter
Exclusion Criteria:
- Major surgery within 4 weeks of the first dose of ibrutinib
- Diagnosed or treated for malignancy other than the indication under study except for: a) Adequately treated non-melanoma skin cancer or lentigo maligna, curatively treated in-situ cancer without evidence of disease; b) Malignancy treated with curative intent and with no known active disease present for >=3 years before the first dose of ibrutinib
- History of stroke or intracranial hemorrhage within 6 months prior to the first dose of ibrutinib
- History of galactose intolerance
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists (for example, phenprocoumon)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Part 1: Ibrutinib+Erythromycin+Voriconazole
Participants will receive oral treatment in six, 28-days cycles.
In Cycle 1, participants will take ibrutinib 560 milligram (mg) (4*140 mg capsules) once daily (QD) from Days 1- 4; on Days 5-11 ibrutinib 140 mg capsule QD in combination with erythromycin 500 mg tablet 3 times daily (TID); on Days 12-13 ibrutinib 140 mg capsule QD; on Days 14-18 ibrutinib 560 mg (4*140 mg capsules) QD; on Days 19-25 ibrutinib 140 mg capsule QD in combination with voriconazole 200 mg tablet twice daily (BD); on Days 26-27 ibrutinib 140 mg capsule orally QD; and on Day 28 and in subsequent treatment Cycles (2-6) participants will continue oral treatment with ibrutinib 420 mg or 560 mg QD (depending on the subtype of B-cell malignancy).
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Ibrutinib capsule (at dose level of 140 or 420 or 560 mg) will be taken orally QD up to six, 28-days cycles.
Other Names:
Erythromycin 500 mg tablet will be taken orally TID (Part1 Cycle 1: on Days 5-10 and morning dose on Day 11; Part2 Cycle 1: on Days 5-17 and morning dose on Day 18).
Other Names:
Voriconazole 200 mg tablet will be taken orally BD (Part1 Cycle 1: on Days 19-25; Part2 Cycle 1: on Days 5-17).
Other Names:
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Experimental: Part 2: Ibrutinib+ Erythromycin+Voriconazole
Participants will receive oral treatment in six, 28-days cycles.
In Cycle 1, participants will take ibrutinib 560 mg (4*140 mg capsules) QD from Days 1- 4; on Days 5-18 ibrutinib 560 mg (4*140 mg capsules) QD in combination with either erythromycin 500 mg tablet TID (Group 1) or voriconazole 200 mg tablet BD (Group 2); on Day 19 and in subsequent treatment Cycles (2-6) participants will continue oral treatment with ibrutinib 420 mg or 560 mg QD (depending on the subtype of B-cell malignancy).
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Ibrutinib capsule (at dose level of 140 or 420 or 560 mg) will be taken orally QD up to six, 28-days cycles.
Other Names:
Erythromycin 500 mg tablet will be taken orally TID (Part1 Cycle 1: on Days 5-10 and morning dose on Day 11; Part2 Cycle 1: on Days 5-17 and morning dose on Day 18).
Other Names:
Voriconazole 200 mg tablet will be taken orally BD (Part1 Cycle 1: on Days 19-25; Part2 Cycle 1: on Days 5-17).
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Time Frame: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
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The Cmax is the maximum observed plasma concentration.
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Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
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Minimum Observed Plasma Concentration (Cmin) of Ibrutinib
Time Frame: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
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The Cmin is the minimum observed plasma concentration.
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Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
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Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
Time Frame: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
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The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
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Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
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Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Ibrutinib
Time Frame: Cycle 1: 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
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The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.
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Cycle 1: 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
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Metabolite to Parent (M/P) Ratio of Ibrutinib
Time Frame: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
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Ratio of ibrutinib metabolite concentration to parent compound (ibrutinib) concentration will be assessed.
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Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Partial Area Under the Plasma Concentration-Time Curve Between 2 Defined Timepoints (AUC [t1 and t2]) of Voriconazole
Time Frame: Cycle 1: 0 hour (hr) pre-dose on Day 5; 0 hr pre-dose, 0.5,1,2,3,4,6 and 24 hrs post-dose on Day 18 and 25
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The AUC (t1 and t2) is the partial area under the plasma concentration-time curve from time 't1' to 't2' hours.
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Cycle 1: 0 hour (hr) pre-dose on Day 5; 0 hr pre-dose, 0.5,1,2,3,4,6 and 24 hrs post-dose on Day 18 and 25
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Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Screening up to end of study (up to 8 months)
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An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
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Screening up to end of study (up to 8 months)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 19, 2015
Primary Completion (Actual)
June 24, 2016
Study Completion (Actual)
June 24, 2016
Study Registration Dates
First Submitted
March 2, 2015
First Submitted That Met QC Criteria
March 2, 2015
First Posted (Estimate)
March 6, 2015
Study Record Updates
Last Update Posted (Actual)
June 26, 2017
Last Update Submitted That Met QC Criteria
June 23, 2017
Last Verified
June 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, B-Cell
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Gastrointestinal Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Anti-Bacterial Agents
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Protein Synthesis Inhibitors
- Hormone Antagonists
- Antifungal Agents
- Steroid Synthesis Inhibitors
- 14-alpha Demethylase Inhibitors
- Erythromycin
- Erythromycin Estolate
- Erythromycin Ethylsuccinate
- Erythromycin stearate
- Voriconazole
Other Study ID Numbers
- CR106609
- PCI-32765LYM1003 (Other Identifier: Janssen Research & Development, LLC)
- 2015-000325-36 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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