A Randomized, Open Label, Two Arm, Single Dose, Crossover, Bioequivalence Study of Ayana Pharma's Doxorubicin Hydrochloride Liposome Injection (LC-101) (Investigational Product) and the US Reference Standard Doxorubicin Hydrochloride Liposome Injection (Sun Pharma), in Subjects With Ovarian Cancer.
Overview
- Phase
- Phase 1
- Intervention
- Doxorubicin Hydrochloride Liposome Injection
- Conditions
- Ovarian Cancer Recurrent
- Sponsor
- Ayana Pharma Ltd.,
- Enrollment
- 52
- Locations
- 15
- Primary Endpoint
- Assessment of bioequivalence using Cmax of encapsulated and free doxorubicin in plasma
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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 is a randomized, open label, two arm, single dose, crossover bioequivalence study. This study will be conducted in female subjects aged 18 to 65 years diagnosed with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy and who are already receiving or scheduled to start therapy with Doxorubicin Hydrochloride Liposome Injection product. Each subject will be randomized to one of the two treatment sequences (RT or TR) according to a randomization scheme prepared prior to start of the trial. Serial blood samples for determination of free and liposomal encapsulated doxorubicin plasma concentration for PK analysis will be obtained in each cycle., This study has an adaptive 2-stage design. A sufficient number of subjects with ovarian cancer shall be recruited to have approximately 42 evaluable subjects completing all follow up procedures (Stage 1). An interim analysis of free and encapsulated doxorubicin will be performed at the end of Stage 1. If the bioequivalence of encapsulated and free doxorubicin has been established, then the study will be stopped. Otherwise, the study may continue into Stage 2 with additional number of ovarian cancer subjects. A final evaluation of bioequivalence based on free and encapsulated doxorubicin will be performed at the end of Stage 2 and will include all enrolled subjects completing the study. Bioequivalence criteria: the 94.12% confidence interval of the ratio of geometric means of TEST to REFERENCE for Cmax, AUC0-t, AUC0-∞, for free and encapsulated doxorubicin should be between 80.00% and 125.00%.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult female subjects between 18 to 65 years of age (both inclusive) at the time of screening visit.
- •Subjects with histologically or cytological proven ovarian cancer, whose disease has progressed or recurred after platinum-based chemotherapy and scheduled to start therapy with or who are already receiving an approved dose of 50 mg per meter square Doxorubicin Hydrochloride Liposome Injection product.
- •Subjects expected to be able to receive both doses of Doxorubicin Hydrochloride Liposome Injection.
- •Subjects eligible for receiving a dose of 50 mg per meter square of Doxorubicin Hydrochloride Liposome Injection.
- •Subjects with Performance less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- •Cardiac function (LVEF) greater than or equal to 50 percentage.
- •Adequate renal, hepatic and bone marrow function without blood product or hematopoietic growth factor support.
- •Subjects able to understand the investigational nature of this study.
- •Availability of subject for the entire study period and willingness to adhere to protocol requirements.
- •For subjects of child-bearing potential, serum beta HCG pregnancy test at screening and urine pregnancy test prior to dosing must be negative and subjects agree to use an acceptable and effective approved method of contraception
Exclusion Criteria
- •Subjects with history or presence of significant:
- •Allergy or significant history of hypersensitivity or idiosyncratic reactions to a conventional formulation of Doxorubicin Hydrochloride and/or any components of Doxorubicin Hydrochloride liposome injection.
- •Clinically significant pulmonary, hepatic, renal, bone marrow, gastrointestinal, endocrine, immunologic, dermatologic, musculoskeletal, neurological or psychiatric disease.
- •Impaired cardiac function
- •Alcohol dependence, alcohol abuse or drug abuse or addiction with any recreational drug within the past one year.
- •Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, p. carinii or other microorganism (bacterial, viral or fungal).
- •Clinically significant illness (except ovarian cancer) within four weeks prior to dosing.
- •Prior radiation therapy to mediastinum
- •Concomitant use of other cytotoxic or cytostatic drugs or of radiotherapy within four weeks prior to dosing
- •Subject under treatment of myelotoxic drugs, other than doxorubicin (liposomal).
Arms & Interventions
Reference Product - R
Doxorubicin Hydrochloride Liposome Injection (Sun Pharma); 20 mg/10 mL i.e. 2 mg/mL (50mg/m2 dose). As this is a cross over study, subjects receiving in Cycle 1 the Reference Product (doxorubicin hydrochloride liposome injection SunPharma), will receive in Cycle 2 the Test Product (doxorubicin hydrochloride liposome injection (Ayana); after at least 4 weeks (RT).
Intervention: Doxorubicin Hydrochloride Liposome Injection
Test Product - T
Doxorubicin Hydrochloride Liposome Injection (Ayana Pharma Ltd); 20 mg/10 mL i.e. 2 mg/mL (50mg/m2 dose). As this is a cross over study, subjects receiving in Cycle 1 the Test Product (doxorubicin hydrochloride liposome injection (Ayana)will receive in Cycle 2 the Reference Product (doxorubicin hydrochloride liposome injection SunPharma); after at least 4 weeks (RT).
Intervention: Doxorubicin Hydrochloride Liposome Injection
Outcomes
Primary Outcomes
Assessment of bioequivalence using Cmax of encapsulated and free doxorubicin in plasma
Time Frame: Throughout 15 days after both dosing.
Assessment of bioequivalence of LC-101 (TEST Product) in comparison to the US Reference standard (REFERENCE product). Bioequivalence will be assessed using maximum plasma doxorubicin concentration (Cmax) of encapsulated and free doxorubicin measurements in plasma.
Assessment of bioequivalence using AUC (0-t) of encapsulated and free doxorubicin in plasma
Time Frame: Throughout 15 days after both dosing.
Assessment of bioequivalence of LC-101 (TEST Product) in comparison to the US Reference standard (REFERENCE product). Bioequivalence will be assessed using areas under the plasma concentration versus time curve calculated from 0 to the last measurable observation (AUC 0-t) of encapsulated and free doxorubicin measurements in plasma.
Assessment of bioequivalence using AUC (0-inf) of encapsulated and free doxorubicin in plasma
Time Frame: Throughout 15 days after both dosing.
Assessment of bioequivalence of LC-101 (TEST Product) in comparison to the US Reference standard (REFERENCE product). Bioequivalence will be assessed using areas under the plasma concentration versus time curve calculated from 0 to infinity (AUC 0-inf) of encapsulated and free doxorubicin measurements in plasma.
Secondary Outcomes
- Assessment of bioequivalence using Cmax of total doxorubicin in plasma(Throughout 15 days after both dosing.)
- Assessment of bioequivalence using AUC (0-inf) total doxorubicin as secondary analyte(Throughout 15 days after both dosing.)
- Assessment of bioequivalence using AUC (0-t) of total doxorubicin in plasma(Throughout 15 days after both dosing.)
- Assessment of safety(Troughout 42 days after first dosing)