Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection

September 22, 2016 updated by: Dr. Reddy's Laboratories Limited

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.

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 .

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

49

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Andhra Pradesh
      • Vijaywada, Andhra Pradesh, India
        • City Cancer Center
    • Gujarat
      • Surat, Gujarat, India
        • Nirmal Hospital Pvt Ltd
    • Karnataka
      • Bangalore, Karnataka, India
        • Srinivasam Cancer Care Hospitals India Private Limited
      • Erode, Karnataka, India
        • Erode Cancer Center
    • Maharahtra
      • Nagpur, Maharahtra, India
        • Cancer Clinic and Nursing Home & Jasleen Hospital
    • Maharashtra
      • Nashik, Maharashtra, India
        • Curie Manavta Cancer Centre
    • Orissa
      • Cuttack, Orissa, India
        • Acharya HariHar Regional Cancer Centre
    • Tamil Nadu
      • Madurai, Tamil Nadu, India
        • Meenakshi Mission Hospital & Research Centre
      • Trichy, Tamil Nadu, India
        • Dr. G. Viswanathan Speciality Hospitals
    • Telangana
      • Hyderabad, Telangana, India, 500034
        • Bibi General Hospital
      • Hyderabad, Telangana, India
        • MNJ Institute of Oncology & Regional Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
58 days
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)
58 days
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
58 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of treatment-emergent adverse events ( TEAEs)
Time Frame: 58 days
58 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dr. Reddy's Laboratories Limited

Investigators

  • Study Director: Ashis Patnaik, MBBS, MD, Dr. Reddy's Laboratories Limited

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2014

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

September 22, 2014

First Submitted That Met QC Criteria

October 8, 2014

First Posted (Estimate)

October 9, 2014

Study Record Updates

Last Update Posted (Estimate)

September 23, 2016

Last Update Submitted That Met QC Criteria

September 22, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 591-13

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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