Bioequivalence study of Doxorubicin HCL Liposome Inj 20mg/10mL(Dose:50mg/m2) of Emcure PharmaLtd.,India, compared to that of Doxorubicin HCL Liposome Inj for IV Infusion20mg/10mL(Dose:50mg/m2) OFJANSSEN-CILAG INTERNATIONAL NV BELGIUM, in female patients with ovarian cancer in fasting conditio
- Conditions
- Health Condition 1: null- ADVANCED OVARIAN CANCER WHO HAVE FAILED A FIRST-LINEPLATINUM-BASED CHEMOTHERAPY REGIMEN AND WHO ARE ALREADYRECEIVING OR SCHEDULED TO START DOXORUBICINHYDROCHLORIDE LIPOSOME INJECTIO
- Registration Number
- CTRI/2018/06/014575
- Lead Sponsor
- Emcure Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 67
1. Female patients, 18 to 75 years of age (both inclusive) and having a Body Mass
Index (BMI) at least 17 kg/m2.
2. Have histologically or cytologically confirmed advanced ovarian cancer
3. Patients with advanced ovarian cancer who have failed a first-line platinum-based
chemotherapy regime and who are already receiving or scheduled to start
Doxorubicin Hydrochloride liposomal injection 50 mg/m2 dose as monotherapy as
per Investigator judgment.
4. Patients with life expectancy for at least 3 months.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (The
woman should be ambulatory, capable of all self-care, up for more than 50% of
waking hours. She may or may not be able to carry out any work activities).
6. Patients should preferably be on monotherapy. However, cancer patients receiving
concomitant medications are allowed to participate provided:
The concomitant medication and their dosing regimen are expected to be same for
both the study periods.
The concomitant medications do not interfere with the study drug (If concomitant
medication is required during the study period, the patients will be treated
accordingly, and a decision to continue or discontinue the patients will be made
by the investigator).
7. Availability of patient for the entire study period and willingness to adhere to
Protocol requirements as evidenced by the written ICF duly signed by the patient.
8. Either the female is of non-child bearing potential (females having documented
history of surgical sterilization or are postmenopausal (12 months of amenorrhea
after the last menstrual period) or if the female is of child bearing potential, then she
is eligible if:
Patient has used an effective method of contraception or abstinence from at least 4
weeks prior to study drug administration. Effective method includes:
Tubal sterilization (tubal ligation performed more than one month before Study
Day 1; transcervical tubal occlusion procedure performed more than six months
before Study Day 1)
Intrauterine Device (IUD)
Progestin Implant (i.e. Implanon or its equivalent)
Progestin injection or progestin oral contraceptive pill + one barrier method
(cervical cap, diaphragm, contraceptive sponge or vaginal spermicide + a male or
female condom)
Two barrier methods used together (cervical cap, diaphragm, contraceptive
sponge or vaginal spermicide + a male or female condom)
Absolute sexual abstinence (no sexual intercourse or genital contact with a male
partner)
Patient is willing to avoid pregnancies during the study and up to 06 months after
the last dose of study drug by use of an effective method of permitted
contraception or abstinence.
Patients having negative pregnancy test.
Patients will be excluded from the study, if they meet any of the following criteria:
1. Patients who have a history of hypersensitivity or idiosyncratic reactions to a conventional or novel liposomal formulation of Doxorubicin HCl and its
excipients.
2. Prior Doxorubicin (or other anthracyclines) exposure that would result in a total
lifetime exposure of 550 mg/m2 or more after four cycles of treatment.
3. Patients who require any dose modifications (Dose other than 50 mg/m2)
4. Have received treatment with radiation therapy, chemotherapy, immunotherapy in
less than 4 weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C)
5. If any patient whose weight changes during the study requiring a ± 5% dose
adjustment will be discontinued from the study and excluded from the analysis.
6. If any signs or symptoms of extravasation have occurred, the infusion should be
immediately terminated and the patient will be discontinued from the study and
excluded from the analysis.
7. Known active brain metastasis including leptomeningeal involvement (patients
with brain metastases can only be enrolled if they are treated and stable for >8
weeks and who currently do not require steroid or radiation therapy)
8. Clinically significant Pre-existing toxicity by National Cancer Institute (NCI)
Common Terminology Criteria for Adverse Events (CTCAE) criteria. Mild to
moderate Pre-existing toxicity can be allowed only if in the opinion of
investigator, it will not require dose modification, will not interfere with the study
assessment and will not pose undue safety concerns to the patient. (â??Palmarâ??
plantar erythrodysesthesiaâ?? and â??Stomatitisâ?? of grade 2 and above requires dose
modification, hence not allowed).
9. Patients with significantly impaired hepatic or renal function.
10. Significant history or current evidence of chronic - infectious,
cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic
(endocrine), hematological, gastrointestinal, immunological or psychiatric
diseases, or organ dysfunction.
11. Laboratory parameters:
Patients with ANC < 1500/mm3
Platelet count < 100,000/mm3
Hemoglobin < 9.0 g/dl
Bilirubin >2.5 x ULN or if any dose modification required due to abnormal
bilirubin levels
Alkaline phosphatase, ALT, AST > 2.5 x ULN
For other laboratory parameters, the patient can be included if the values are
clinically non-significant in the opinion of investigator.
12. Patients with any of the following cardiac conditions:
Left ventricular ejection fraction (LVEF) <50 % as determined by ECHO
Clinically significant QTc prolongation, Uncontrolled arrhythmias, Acute
Ischemia, or other significant abnormalities as determined by ECG.
Prior history of Unstable angina in past 06 months.
Prior history of Myocardial infarction within the past 06 months.
New York State Heart Association (NYHA) class II-IV heart failure.
Any other cardiac illness that could lead to a safety risk to the patient in case
of enrolment in the study.
13. Pregnant or lactating woman.
14. Females of childbearing potential unwilling to use acceptable contraception (as
identified in the protocol)
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the bioequivalence of Doxorubicin Hydrochloride Liposome <br/ ><br>concentrate for solution for infusion 2 mg/mL at a dose of 50mg/m2 of Emcure <br/ ><br>Pharmaceuticals Ltd., India, compared to that of Caelyx 2 mg/mL concentrate for <br/ ><br>solution for infusion of Janssen-Cilag <br/ ><br>International NV, Belgium., in female patients with advanced ovarian cancer <br/ ><br>injection under fasting condition.Timepoint: Pharmacokinetic sampling shall occur within 02 hours pre-dose, 0.00 and post dose <br/ ><br>at 00.17, 00.33, 00.50, 00.67, 00.83, <br/ ><br>01.00, 01.08, 01.25, 01.50, 01.75, 02.00, 03.00, 04.00, 06.00, 08.00, 12.00, 24.00, 48.00, 96.00, 144.00, 192.00,240.00, 288.00 and 336.00 hours.
- Secondary Outcome Measures
Name Time Method To monitor the safety and tolerability of a single dose administered in female <br/ ><br>patients with advanced ovarian cancer who have failed a first-line platinum-based <br/ ><br>chemotherapy regimen and who are already receiving or scheduled to start therapy <br/ ><br>with the doxorubicin hydrochloride liposome injection under fasting conditionsTimepoint: Measurement of seated blood pressure, pulse rate and wellbeing <br/ ><br>enquiry will be performed prior to check-in, prior to start of infusion, after the <br/ ><br>completion of infusion, at 02.00, 04.00, 08.00, 12.00 hours (±40 minutes) from the start of <br/ ><br>infusion, at check-out and during ambulatory of both the periods and monitor AEs, SAEs.