An Open-Label Study to Assess the Effect of CYP3A4 Induction on the Pharmacokinetics of VELCADE (Bortezomib)

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00608907
First received: January 23, 2008
Last updated: January 26, 2012
Last verified: January 2012
  Purpose

The primary purpose of this Phase I study is to evaluate the effect of the co-administration of CYP3A4 inducers on the pharmacokinetics profile of VELCADE (bortezomib). Rifampicin will be used to assess the effect of a strong CYP3A4 inducer and dexamethasone to assess the effect of a relatively weak inducer. This study is also to evaluate the impact of CYP3A4 inducers on the pharmacodynamics (PD) of VELCADE and the safety profile of VELCADE.


Condition Intervention Phase
Multiple Myeloma
Non-Hodgkin's Lymphoma
Drug: bortezomib
Drug: bortezomib, rifampicin
Drug: bortezomib, dexamethasone
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Study to Assess the Effect of CYP3A4 Induction on the Pharmacokinetics of VELCADE (Bortezomib)

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Area Under the Plasma Concentration-time Curve (AUC) 0-72 Hours [ Time Frame: Cycle 3 day 14 (72 hours post last dose) ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: September 2007
Study Completion Date: April 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VELCADE
Control arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle.
Drug: bortezomib
1.3 mg/m^3 on days 1, 4, 8, 11 over a 21-day treatment cycle
Other Name: VELCADE
Experimental: VELCADE + rifampicin
Treatment Arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg once daily days 4 to 10 in cycle 3.
Drug: bortezomib, rifampicin
bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg once daily days 4 to 10 in cycle 3
Other Names:
  • bortezomib
  • rifampicin
Experimental: VELCADE + dexamethasone
Treatment arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg once daily days 1 to 4, and 9 to 12 in cycle 3.
Drug: bortezomib, dexamethasone
bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg once daily days 1 to 4, and 9 to 12 in cycle 3
Other Names:
  • bortezomib
  • dexamethasone

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female of at least 18 years of age.
  • Has documented relapsed or refractory multiple myeloma or NHL following prior anti-neoplastic treatment.
  • Female patients must be post menopausal for at least 1 year (must not have had a natural menses for at least 12 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; have a negative serum β-HCG or a negative urine pregnancy test at screening. (an alternative to oral contraceptives should be used if the patient is randomized to Arm B with rifampicin).
  • Male patients must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study.
  • Must be able to swallow capsules/tablets whole (without chewing, crushing, or opening).
  • Agree to refrain from the use of any methylxanthine-containing products, including caffeine (e.g., chocolate bars or beverages, coffee, teas, or colas), on Day 11 of Cycles 2 and 3.
  • Agree to refrain from the use of any products containing nicotine, alcohol, quinine, grapefruit juice, or Seville oranges from 7 days before the first administration of VELCADE through completion of the 72-hour PK blood sample collection (post Day 11 VELCADE dose) in Cycle 3.

Exclusion Criteria:

  • Diagnosis or treatment of a malignancy other than multiple myeloma or NHL within 1 year of randomization, or who have previously been diagnosed with a malignancy other than multiple myeloma or NHL and have any radiographic or biochemical marker evidence of malignancy.
  • History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric, or metabolic disturbances.
  • Known or suspected hypersensitivity or intolerance to rifampicin and/or other antibiotics, corticosteroids, boron or mannitol.
  • Peripheral neuropathy or neuropathic pain Grade 2 or higher.
  • Preplanned surgery or procedures that would interfere with the conduct of the study or major surgery within 2 weeks before randomization.
  • History of disallowed therapies:

    • Prior treatment with VELCADE.
    • Any drugs or agents that inhibit (e.g., cimetidine, erythromycin, fluoxetine, ketoconazole, paroxetine) or induce (e.g., carbamazepine, glucocorticoids, phenobarbital, phenytoin, St. John's Wort) CYP2C19 or CYP3A4 within 28 days before the first administration of VELCADE.
    • Any exposure to rifampicin or corticosteroids within 28 days of screening.
    • Have received an investigational agent or used an investigational medical device within 28 days before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study.
  • Female patient who is pregnant or breastfeeding.
  • Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00608907

Locations
Israel
Hematology Institute - Davidoff Center - Rabin Medical Center
Petach Tikva, Israel, 49100
Italy
Divisione di Ematologia - Ospedale S Eugenio - P. le dell'Umanesimo
Rome, Italy, 10001
Poland
Medical Academy - Dept of Hematology and Transplantology
Gdansk, Poland, 80-952
Klinika Nowotworow Ukladu - Chlonnego - Centrum Onkologii - Instytut
Warszawa, Poland, 02-781
South Africa
Hematological Oncology
Parow, Cape Town, South Africa
Department of Hematology - University of the Free State
Bloemfontein, South Africa, 9300
Department of Medical Oncology - Ward 51 - Pretoria Academic Hospital
Pretoria, South Africa, 0001
United Kingdom
Plymouth Hospitals NHS Trust - Derriford Hospital
Derriford, Plymouth, United Kingdom, PL68DH
Hematology Department Combined Laboratories - Derriford Hospital
Plymouth, United Kingdom, PL6 8DH
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00608907     History of Changes
Other Study ID Numbers: 26866138-CAN-1006
Study First Received: January 23, 2008
Results First Received: March 29, 2011
Last Updated: January 26, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
BB 1101
Rifampin
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2014