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

NCT02381080 | Completed Phase 1

• 3 other identifiers: CR106609PCI-32765LYM10032015-000325-36
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 6

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).

Conditions

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

Outcome Measures

Primary Outcomes (5)

• Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

  The Cmax is the maximum observed plasma concentration.

  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

• Minimum Observed Plasma Concentration (Cmin) of Ibrutinib

  The Cmin is the minimum observed plasma concentration.

  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

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib

  The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

  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

• 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.

  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

• Metabolite to Parent (M/P) Ratio of Ibrutinib

  Ratio of ibrutinib metabolite concentration to parent compound (ibrutinib) concentration will be assessed.

  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 Outcomes (2)

• Partial Area Under the Plasma Concentration-Time Curve Between 2 Defined Timepoints (AUC [t1 and t2]) of Voriconazole

  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

• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Screening up to end of study (up to 8 months)

Study Arms (2)

Part 1: Ibrutinib+Erythromycin+Voriconazole

EXPERIMENTAL

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).

Drug: Ibrutinib; Drug: Erythromycin; Drug: Voriconazole

Part 2: Ibrutinib+ Erythromycin+Voriconazole

EXPERIMENTAL

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).

Drug: Ibrutinib; Drug: Erythromycin; Drug: Voriconazole

Interventions

Ibrutinib DRUG

Ibrutinib capsule (at dose level of 140 or 420 or 560 mg) will be taken orally QD up to six, 28-days cycles.

Also known as: Imbruvica, PCI-32765, JNJ-54179060

Part 1: Ibrutinib+Erythromycin+Voriconazole; Part 2: Ibrutinib+ Erythromycin+Voriconazole

Erythromycin DRUG

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).

Also known as: Erythrocin

Part 1: Ibrutinib+Erythromycin+Voriconazole; Part 2: Ibrutinib+ Erythromycin+Voriconazole

Voriconazole DRUG

Voriconazole 200 mg tablet will be taken orally BD (Part1 Cycle 1: on Days 19-25; Part2 Cycle 1: on Days 5-17).

Also known as: VFEND

Part 1: Ibrutinib+Erythromycin+Voriconazole; Part 2: Ibrutinib+ Erythromycin+Voriconazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (6)

Unknown Facility

N/a N/a, Canada

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Petrozavodsk, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Pamplona, Spain

Location

Related Links

• A Drug-Drug Interaction Study of Ibrutinib With Moderate and Strong CYP3A Inhibitors in Patients With B-cell Malignancy

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Waldenstrom Macroglobulinemia

Interventions

ibrutinib; Erythromycin; Voriconazole

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trials

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 6, 2015
• Study Start: May 19, 2015
• Primary Completion: June 24, 2016
• Study Completion: June 24, 2016
• Last Updated: June 26, 2017

Record last verified: 2017-06

Locations

ES (2); CA (1); RU (3)