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Interaction Study of Ibrutinib and Cytochrome P450 (CYP) 3A Inhibitors in Participants With B-cell Malignancy

Primary Purpose

B-Cell Chronic Lymphocytic Leukemia

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Ibrutinib
Erythromycin
Voriconazole
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-Cell Chronic Lymphocytic Leukemia focused on measuring B-Cell Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Waldenstrom's Macroglobulinemia, Ibrutinib, IMBRUVICA, PCI-32765, JNJ-54179060

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1: Ibrutinib+Erythromycin+Voriconazole

Part 2: Ibrutinib+ Erythromycin+Voriconazole

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
The Cmax is the maximum observed plasma concentration.
Minimum Observed Plasma Concentration (Cmin) of Ibrutinib
The Cmin is the minimum observed plasma concentration.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Ibrutinib
The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.
Metabolite to Parent (M/P) Ratio of Ibrutinib
Ratio of ibrutinib metabolite concentration to parent compound (ibrutinib) concentration will be assessed.

Secondary Outcome Measures

Partial Area Under the Plasma Concentration-Time Curve Between 2 Defined Timepoints (AUC [t1 and t2]) of Voriconazole
The AUC (t1 and t2) is the partial area under the plasma concentration-time curve from time 't1' to 't2' hours.
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.

Full Information

First Posted
March 2, 2015
Last Updated
June 23, 2017
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02381080
Brief Title
Interaction Study of Ibrutinib and Cytochrome P450 (CYP) 3A Inhibitors in Participants With B-cell Malignancy
Official Title
A Drug-drug Interaction Study of Ibrutinib With Moderate and Strong CYP3A Inhibitors in Patients With B-cell Malignancy
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
May 19, 2015 (Actual)
Primary Completion Date
June 24, 2016 (Actual)
Study Completion Date
June 24, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-Cell Chronic Lymphocytic Leukemia
Keywords
B-Cell Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Waldenstrom's Macroglobulinemia, Ibrutinib, IMBRUVICA, PCI-32765, JNJ-54179060

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Ibrutinib+Erythromycin+Voriconazole
Arm Type
Experimental
Arm Description
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).
Arm Title
Part 2: Ibrutinib+ Erythromycin+Voriconazole
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
Imbruvica, PCI-32765, JNJ-54179060
Intervention Description
Ibrutinib capsule (at dose level of 140 or 420 or 560 mg) will be taken orally QD up to six, 28-days cycles.
Intervention Type
Drug
Intervention Name(s)
Erythromycin
Other Intervention Name(s)
Erythrocin
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Voriconazole
Other Intervention Name(s)
VFEND
Intervention Description
Voriconazole 200 mg tablet will be taken orally BD (Part1 Cycle 1: on Days 19-25; Part2 Cycle 1: on Days 5-17).
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Description
The Cmax is the maximum observed plasma concentration.
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
Title
Minimum Observed Plasma Concentration (Cmin) of Ibrutinib
Description
The Cmin is the minimum observed plasma concentration.
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
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
Description
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
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
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Ibrutinib
Description
The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.
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
Title
Metabolite to Parent (M/P) Ratio of Ibrutinib
Description
Ratio of ibrutinib metabolite concentration to parent compound (ibrutinib) concentration will be assessed.
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
Secondary Outcome Measure Information:
Title
Partial Area Under the Plasma Concentration-Time Curve Between 2 Defined Timepoints (AUC [t1 and t2]) of Voriconazole
Description
The AUC (t1 and t2) is the partial area under the plasma concentration-time curve from time 't1' to 't2' hours.
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
Title
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Screening up to end of study (up to 8 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trials
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
N/a N/a
Country
Canada
City
Moscow
Country
Russian Federation
City
Petrozavodsk
Country
Russian Federation
City
St. Petersburg
Country
Russian Federation
City
Madrid
Country
Spain
City
Pamplona
Country
Spain

12. IPD Sharing Statement

Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_7051&studyid=9493&filename=CR106609_CSR.pdf
Description
A Drug-Drug Interaction Study of Ibrutinib With Moderate and Strong CYP3A Inhibitors in Patients With B-cell Malignancy

Learn more about this trial

Interaction Study of Ibrutinib and Cytochrome P450 (CYP) 3A Inhibitors in Participants With B-cell Malignancy

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