Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection

Phase 1

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Test Product - T	Doxorubicin Hydrochloride Liposome Injection	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.
Reference Product - R	Doxorubicin Hydrochloride Liposome Injection	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.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic ( PK ) parameter : the maximum plasma doxorubicin concentration ( Cmax ) [ Time frame : 2 cycles ]	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)	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)	58 days	The study endpoint will use the PK parameter ( AUC 0-Inf) for free doxorubicin and liposome encapsulated doxorubicin

Secondary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events ( TEAEs)	58 days

Locations (11): Dr. G. Viswanathan Speciality Hospitals
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Trichy, Tamil Nadu, India
Meenakshi Mission Hospital & Research Centre
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Madurai, Tamil Nadu, India
City Cancer Center
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Vijaywada, Andhra Pradesh, India
Erode Cancer Center
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Erode, Karnataka, India
Acharya HariHar Regional Cancer Centre
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Cuttack, Orissa, India
Nirmal Hospital Pvt Ltd
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Surat, Gujarat, India
Srinivasam Cancer Care Hospitals India Private Limited
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Bangalore, Karnataka, India
Cancer Clinic and Nursing Home & Jasleen Hospital
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Nagpur, Maharahtra, India
Curie Manavta Cancer Centre
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Nashik, Maharashtra, India
Bibi General Hospital
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Hyderabad, Telangana, India
MNJ Institute of Oncology & Regional Cancer Centre
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Hyderabad, Telangana, India