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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00608907
• Other study ID #: 26866138-CAN-1006
• Status: Completed
• Phase: Phase 1
• First received: January 23, 2008
• Last updated: January 26, 2012
• Start date: September 2007
• Est. completion date: April 2010

Study information

• Verified date: January 2012
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: April 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ß-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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• bortezomib
1.3 mg/m^3 on days 1, 4, 8, 11 over a 21-day treatment cycle
• 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
• 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

Locations

Country	Name	City	State
Israel	Hematology Institute - Davidoff Center - Rabin Medical Center	Petach Tikva
Italy	Divisione di Ematologia - Ospedale S Eugenio - P. le dell'Umanesimo	Rome
Poland	Medical Academy - Dept of Hematology and Transplantology	Gdansk
Poland	Klinika Nowotworow Ukladu - Chlonnego - Centrum Onkologii - Instytut	Warszawa
South Africa	Department of Hematology - University of the Free State	Bloemfontein
South Africa	Hematological Oncology	Parow	Cape Town
South Africa	Department of Medical Oncology - Ward 51 - Pretoria Academic Hospital	Pretoria
United Kingdom	Plymouth Hospitals NHS Trust - Derriford Hospital	Derriford	Plymouth
United Kingdom	Hematology Department Combined Laboratories - Derriford Hospital	Plymouth

Sponsors (2)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Countries where clinical trial is conducted

Israel,  Italy,  Poland,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration-time Curve (AUC) 0-72 Hours		Cycle 3 day 14 (72 hours post last dose)	No