CTRI/2015/05/005758 [Registered on: 08/05/2015] Trial Registered Prospectively
Last Modified On:
27/04/2016
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study of Bortezomib for Injection 3.5 mg/vial in previously
untreated Multiple Myeloma and/or Relapsed/Refractory Multiple Myeloma patients.
Scientific Title of Study
A Multicentre, Open label, Balanced, Randomized, Two-treatment, Two-period, Single dose,
Crossover, Bioequivalence study of Bortezomib for Injection 3.5 mg/vial of Dr. Reddy’s
Laboratories Limited, India and VELCADE® (bortezomib) for Injection 3.5 mg/vial (Distributed
by: Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, MA 02139) in previously
untreated Multiple Myeloma and/or Relapsed/Refractory Multiple Myeloma patients.
Patients will receive a single subcutaneous (SC) dose, 1.3 mg/m2 of Bortezomib, either
Test or Reference Product as per the randomization schedule on Day 32 (Period 1) in abdominal region by trained staff. Patients will receive an alternate treatment (either
Test or Reference) on Day 53 (Period 2) in abdominal region by trained staff.
The time of administration of dose on Day 1should be similar for all subsequent dosing.Thirty minutes deviation will be allowed.
Comparator Agent
VELCADE® (bortezomib) for Injection 3.5 mg/vial
Patients will receive a single subcutaneous (SC) dose, 1.3 mg/m2 of Bortezomib, either Test or Reference Product as per the randomization schedule on Day 32 (Period 1) in abdominal region by trained staff. Patients will receive an alternate treatment (either Test or Reference) on Day 53 (Period 2) in abdominal region by trained staff. The time of administration of dose on Day 1should be similar for all subsequent dosing.Thirty minutes deviation will be allowed.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1.Patients with histopathologically/cytologically confirmed multiple myeloma.
2.Adult patients with previously untreated Multiple Myeloma or Relapsed/Refractory
Multiple Myeloma for whom Bortezomib is considered as suitable treatment as per the
Principal Investigator judgement.
3.Patient with an ECOG performance status of 0-2.
4.Patient must have an adequate bone marrow, renal and hepatic function
5.Life expectancy should be ≥3 months.
ExclusionCriteria
Details
1.Known hypersensitivity to Bortezomib, Boron, Tromethamine, Citric acid or to any of
the excipients, Melphalan and Prednisone (for previously untreated Multiple Myeloma
patients)
2.If the patient had undergone prior surgery, radiation, chemotherapy, or other anticancer
therapy within 4 weeks (28 days) prior to the start of Bortezomib therapyin the
study
3.Patients with positive human immunodeficiency virus (HIV) infection.
4.A positive hepatitis screen including hepatitis B surface antigen, HCV and HAV
antibodies.
5.Use of any recreational drugs or history of drug addiction.
6.A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a
QTc interval >450 milliseconds (ms)).
7.A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family
history of Long QT Syndrome)
8.The use of concomitant medications that prolong the QT/QTc interval
9.Acute diffuse infiltrative pulmonary and pericardial disease.
10.Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of
investigational medicinal product for the current study.
11.Patients who are receiving strong CYP3A4/CYP2C19/CYP1A2 – inhibitors and/or
inducers and in whom these drugs are unable to be restricted for the entire study period.
12.Peripheral Neuropathy Grade 1 with pain or Grade 2 and above.
13.End Stage Renal Disease
To assess the Bioequivalence between Bortezomib for Injection 3.5 mg/vial of Dr. Reddy’s Laboratories Limited, India and VELCADE® (bortezomib) for Injection 3.5 mg/vial (Distributed by: Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, MA 02139) in previously untreated Multiple Myeloma and/or Relapsed/Refractory Multiple Myeloma patients.
PK assessment Pre-dose (0.000) and at 0.083, 0.167, 0.333, 0.500, 0.667, 0.833, 1.000, 1.500, 3.000,6.000, 9.000, 12.000, 24.000, 48.000 and 72.000 hrs post dose.
PD assessment:Pre-dose (0.000) and 0.333, 0.500, 1.000, 2.000, 4.000, 12.000, 24.000, 48.000 and 72.000 hrs post-dose.
Secondary Outcome
Outcome
TimePoints
1.To monitor the safety and tolerability of the patients exposed to the Investigational
Medicinal Product.
2.To characterize the Pharmacodynamics (20S Proteasome inhibition) in patients for exploratory purposes
PK assessment Pre-dose (0.000) and at 0.083, 0.167, 0.333, 0.500, 0.667, 0.833, 1.000, 1.500, 3.000,
6.000, 9.000, 12.000, 24.000, 48.000 and 72.000 hrs post dose. PD assessment:Pre-dose (0.000) and 0.333, 0.500, 1.000, 2.000, 4.000, 12.000, 24.000, 48.000 and 72.000 hrs post-dose.
Target Sample Size
Total Sample Size="64" Sample Size from India="64" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
This is a Multicentre, Open label, Balanced, Randomized, Two-Treatement, Two-Period, Single dose, Crossover bioequivalence of the Test Product (Bortezomib for Injection 3.5 mg/vial of Dr. Reddy’s Laboratories Limited, India) relative to that of Reference Product (VELCADE® (bortezomib) for Injection 3.5 mg/vial (Distributed by: Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, MA 02139)) in previously untreated Multiple Myeloma and/or Relapsed/Refractory Multiple Myeloma patients. Reconstitution Procedure: Add 1.4 mL of sterile 0.9% sodium chloride solution to theBortezomib powder contained in the vial. The final reconstituted concentration will be 2.5 mg/mL. The reconstituted product should be a clear and colourless solution free of particulate matter. Reconstitution will be done within 1 hr prior to dosing. Bortezomib 3.5 mg/vial reconstituted solution (with final Bortezomib concentration of 2.5 mg/mL) will be administered subcutaneously in abdomen (right or left). The solution should be injected subcutaneously, at a 45-90° angle. A total of 32 blood samples each of 4 mL will be collected from each patient for PK assessment and 20 samples, each of 3mL for PD assessment during the study. Venous blood samples will be withdrawn for each patient on Day 32 (Period 1) and Day 53 (Period 2) for PK and PD assessments.