ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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 .

Condition or disease Intervention/treatment Phase
Ovarian Epithelial Cancer Recurrent Drug: Doxorubicin Hydrochloride Liposome Injection Phase 1

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  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Study Start Date : July 2014
Actual Primary Completion Date : April 2015
Actual Study Completion Date : August 2015


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.




Primary Outcome Measures :
  1. 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

  2. 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)

  3. 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


Secondary Outcome Measures :
  1. Incidence of treatment-emergent adverse events ( TEAEs) [ Time Frame: 58 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02260544


Locations
India
City Cancer Center
Vijaywada, Andhra Pradesh, India
Nirmal Hospital Pvt Ltd
Surat, Gujarat, India
Srinivasam Cancer Care Hospitals India Private Limited
Bangalore, Karnataka, India
Erode Cancer Center
Erode, Karnataka, India
Cancer Clinic and Nursing Home & Jasleen Hospital
Nagpur, Maharahtra, India
Curie Manavta Cancer Centre
Nashik, Maharashtra, India
Acharya HariHar Regional Cancer Centre
Cuttack, Orissa, India
Meenakshi Mission Hospital & Research Centre
Madurai, Tamil Nadu, India
Dr. G. Viswanathan Speciality Hospitals
Trichy, Tamil Nadu, India
Bibi General Hospital
Hyderabad, Telangana, India, 500034
MNJ Institute of Oncology & Regional Cancer Centre
Hyderabad, Telangana, India
Sponsors and Collaborators
Dr. Reddy's Laboratories Limited
Investigators
Study Director: Ashis Patnaik, MBBS , MD Dr. Reddy's Laboratories Limited

Additional Information:
Responsible Party: Dr. Reddy's Laboratories Limited
ClinicalTrials.gov Identifier: NCT02260544     History of Changes
Other Study ID Numbers: 591-13
First Posted: October 9, 2014    Key Record Dates
Last Update Posted: September 23, 2016
Last Verified: September 2016

Additional relevant MeSH terms:
Genital Diseases, Female
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action