Clinical trial NCT02260544: Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Epithelial Cancer Recurrent
Lead sponsor: Dr. Reddy's Laboratories Limited
Sponsor class: INDUSTRY
First posted: 2014-10-09
Enrollment: 49
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Pharmacokinetic ( PK ) parameter : the maximum plasma doxorubicin concentration ( Cmax ) [ Time frame : 2 cycles ]
timeFrame: 58 days
measure: PK parameter : the areas under the plasma concentration versus time curve calculated from 0 to the last measurable observation ( AUC 0-t)
timeFrame: 58 days
measure: PK parameter : the areas under the plasma concentration versus time curve extrapolated from 0 to infinity ( AUC 0-inf)
timeFrame: 58 days
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events ( TEAEs)
timeFrame: 58 days
Other outcomes:
Locations:
city: Vijaywada
country: India
facility: City Cancer Center
state: Andhra Pradesh
city: Surat
country: India
facility: Nirmal Hospital Pvt Ltd
state: Gujarat
city: Bangalore
country: India
facility: Srinivasam Cancer Care Hospitals India Private Limited
state: Karnataka
city: Erode
country: India
facility: Erode Cancer Center
state: Karnataka
city: Nagpur
country: India
facility: Cancer Clinic and Nursing Home & Jasleen Hospital
state: Maharahtra
city: Nashik
country: India
facility: Curie Manavta Cancer Centre
state: Maharashtra
city: Cuttack
country: India
facility: Acharya HariHar Regional Cancer Centre
state: Orissa
city: Madurai
country: India
facility: Meenakshi Mission Hospital & Research Centre
state: Tamil Nadu
city: Trichy
country: India
facility: Dr. G. Viswanathan Speciality Hospitals
state: Tamil Nadu
city: Hyderabad
country: India
facility: Bibi General Hospital
state: Telangana
city: Hyderabad
country: India
facility: MNJ Institute of Oncology & Regional Cancer Centre
state: Telangana
Study officials:
affiliation: Dr. Reddy's Laboratories Limited
name: Ashis Patnaik, MBBS, MD
role: STUDY_DIRECTOR
References: