Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection

Ovarian Epithelial Cancer Recurrent Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02260544
• Other study ID #: 591-13
• Status: Completed
• Phase: Phase 1
• First received: September 22, 2014
• Last updated: September 22, 2016
• Start date: July 2014
• Est. completion date: August 2015

Study information

• Verified date: September 2016
• Source: Dr. Reddy's Laboratories Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Central Drugs Standard Control OrganizationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 .

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 information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: August 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 60 Years

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

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Epithelial Cancer Recurrent
• Ovarian Neoplasms

Intervention

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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Dr. Reddy's Laboratories Limited

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic ( PK ) parameter : the maximum plasma doxorubicin concentration ( Cmax ) [ Time frame : 2 cycles ]	The study end point will use PK parameter ( Cmax ) for free doxorubicin and liposome encapsulated doxorubicin	58 days	No
Primary	PK parameter : the areas under the plasma concentration versus time curve calculated from 0 to the last measurable observation ( AUC 0-t)	The study endpoint will use the PK parameter ( AUC 0-t) for free doxorubicin and liposome encapsulated doxorubicin ( AUC 0-t)	58 days	No
Primary	PK parameter : the areas under the plasma concentration versus time curve extrapolated from 0 to infinity ( AUC 0-inf)	The study endpoint will use the PK parameter ( AUC 0-Inf) for free doxorubicin and liposome encapsulated doxorubicin	58 days	No
Secondary	Incidence of treatment-emergent adverse events ( TEAEs)		58 days	Yes

External Links

•   CTRI web site India