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Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02260544
Recruitment Status : Completed
First Posted : October 9, 2014
Last Update Posted : September 23, 2016
Sponsor:
Information provided by (Responsible Party):
Dr. Reddy's Laboratories Limited

Tracking Information
First Submitted Date  ICMJE September 22, 2014
First Posted Date  ICMJE October 9, 2014
Last Update Posted Date September 23, 2016
Study Start Date  ICMJE July 2014
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2014)
  • Pharmacokinetic ( PK ) parameter : the maximum plasma doxorubicin concentration ( Cmax ) [ Time frame : 2 cycles ] [ Time Frame: 58 days ]
    The study end point will use PK parameter ( Cmax ) for free doxorubicin and liposome encapsulated doxorubicin
  • PK parameter : the areas under the plasma concentration versus time curve calculated from 0 to the last measurable observation ( AUC 0-t) [ Time Frame: 58 days ]
    The study endpoint will use the PK parameter ( AUC 0-t) for free doxorubicin and liposome encapsulated doxorubicin ( AUC 0-t)
  • PK parameter : the areas under the plasma concentration versus time curve extrapolated from 0 to infinity ( AUC 0-inf) [ Time Frame: 58 days ]
    The study endpoint will use the PK parameter ( AUC 0-Inf) for free doxorubicin and liposome encapsulated doxorubicin
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2014)
Incidence of treatment-emergent adverse events ( TEAEs) [ Time Frame: 58 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection
Official Title  ICMJE A Multicenter, Open Label, Balanced, Randomized, Two-treatment, Two-period, Two-sequence, Single Dose, Cross-over Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection 20mg/10mL of Dr. Reddy's Laboratories Ltd, India, With That of Doxorubicin Hydrochloride Liposome Injection 20 mg/10mL , Manufactured by: Sun Pharmaceutical Ind. Ltd, India; in Ovarian Cancer Patients Whose Disease Has Progressed or Recurred After Platinum Based Chemotherapy and Who Are Already Receiving or Scheduled to Start Therapy With the Reference Listed Drug Under Fasting Condition.
Brief Summary Bioequivalence study is proposed to be carried out on patients of ovarian cancer, who are already receiving or who in the opinion of their treating physicians are candidates for Doxorubicin liposomal injection therapy .
Detailed Description

This study has sequential two stage design. Bioequivalence based on encapsulated doxorubicin will be tested at the end of stage 1. Power analysis will be performed for the primary pharmacokinetic parameters of free Doxorubicin and liposome encapsulated Doxorubicin, for all completed patients before bioequivalence evaluation. If observed power will be >= 80% then two one-sided 90% CI will be calculated for bioequivalence assessment at stage I.

If observed power will be < 80% then bioequivalence will be evaluated at stage I. If bioequivalence met then study will be stopped and if bioequivalence not met, then required additional patients will be enrolled in stage II.

Each patient will be randomized to one of the two treatment sequences ( RT or TR ) according to a randomization scheme prepared prior to the start of the trial. Serial blood samples for determination of free doxorubicin and liposomal encapsulated doxorubicin plasma concentration for PK analysis will be obtained in each cycle .

Bioequivalence Criteria : The 94.12% confidence intervals for the ratio of geometric least squares means of ln-transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf should be within 80.00 to125.00% to conclude the test product is bioequivalent to the reference product.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Epithelial Cancer Recurrent
Intervention  ICMJE Drug: Doxorubicin Hydrochloride Liposome Injection
50mg/m2, IV on Day 1 of each cycle, On Day 1 of Cycle 2 , patients will crossover to the alternate reference or test formulation , After completion of Cycle 2 ( Day 28) , patients will be continued on the treatment of Doxorubicin Hydrochloride Liposome injection upto 4 more cycles if tolerance permits under guidance of their attending physicians.
Study Arms  ICMJE
  • Experimental: Test Product - T

    doxorubicin hydrochloride liposome ( Dr. Reddy's Lab )

    Use the test drug (doxorubicin hydrochloride liposome Injection 20mg/10mL i.e. 2mg/mL from Dr.Reddy's Laboratories Ltd., India) ; then use the reference drug ( doxorubicin hydrochloride liposome Injection 20mg/10mL i.e. 2mg/mL from Sun Pharma ) after at least 4-weeks.

    Intervention: Drug: Doxorubicin Hydrochloride Liposome Injection
  • Active Comparator: Reference Product - R

    doxorubicin hydrochloride liposome ( Sun Pharma )

    Use the reference drug (doxorubicin Hydrochloride Liposome Injection 20mg/10mL i.e. 2mg/mL; from Sun Pharma ) ; then use the test drug ( doxorubicin hydrochloride liposome Injection 20mg/10mL i.e. 2mg/mL from Dr.Reddy's Laboratories Ltd., India) after at least 4 weeks.

    Intervention: Drug: Doxorubicin Hydrochloride Liposome Injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 22, 2016)
49
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2014)
48
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female of Indian Nationality , between 18-60n years of age
  • Able to understand investigational nature of this study and give written informed consent prior to the participation in the trial.
  • Patients with ovarian cancer requiring Doxorubicin and whose disease has progressed or recurred after platinum-based chemotherapy and who are already receiving or scheduled to start therapy with reference listed drug
  • ECOG performance status ≤ 2
  • Cardiac function ( LVEF) ≥ 50%
  • patient with life expectancy of at least 3 months
  • Adequate hematopoietic, renal and liver function

Exclusion Criteria:

  • Prior doxorubicin exposure that would result in a total lifetime exposure of 550mg/m2 or more after four cycles of treatment .
  • Pregnant or breast-feeding female
  • active opportunistic infection with mycobacteria , cytomegalovirus , toxoplasma
  • Impaired cardiac function including any of the following conditions within past 6 months :

    1. Unstable angina
    2. QTc prolongation or other significant ECG abnormalities
    3. Coronary artery bypass graft surgery
  • History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCl or the components of Doxorubicin Hydrochloride liposome injection.
  • known brain metastasis
  • HIV positive antibody or syphilis
  • Patients with significantly impaired hepatic function
  • Clinically significant liver and kidney disease
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02260544
Other Study ID Numbers  ICMJE 591-13
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Reddy's Laboratories Limited
Study Sponsor  ICMJE Dr. Reddy's Laboratories Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ashis Patnaik, MBBS , MD Dr. Reddy's Laboratories Limited
PRS Account Dr. Reddy's Laboratories Limited
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP