CTRI/2018/05/014342 [Registered on: 31/05/2018] Trial Registered Retrospectively
Last Modified On:
31/05/2018
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study of
Capecitabine tablets 500 mg
Scientific Title of Study
An open label, balanced, randomized, two treatment, three sequence, threeperiod, single dose, Semi replicate, cross over, bioequivalence study of Capecitabine tablets 500 mg of Mega Pharma S.A. Chile and Xeloda® (Capecitabine) tablets 500 mg of Roche in metastatic cancer patients under fed conditions
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
AZ/BE/04/17/11
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Guansakaran
Designation
Head - Clinical
Affiliation
​AZIDUS Laboratories Ltd
Address
​AZIDUS Laboratories Ltd.,
No.23rd School Road, Rathinamangalam,
Behind Tagore Engg. College
(Via) Vandalur, Kelambakkam Road,
Chennai - 600 048
Kancheepuram TAMIL NADU 600 048 India
Phone
8056043873
Fax
Email
gunasakaran@azidus.com
Details of Contact Person Scientific Query
Name
Dr Guansakaran
Designation
Head - Clinical
Affiliation
​AZIDUS Laboratories Ltd
Address
​AZIDUS Laboratories Ltd.,
No.23rd School Road, Rathinamangalam,
Behind Tagore Engg. College
(Via) Vandalur, Kelambakkam Road,
Chennai - 600 048
Kancheepuram TAMIL NADU 600 048 India
Phone
8056043873
Fax
Email
gunasakaran@azidus.com
Details of Contact Person Public Query
Name
Dr Guansakaran
Designation
Head - Clinical
Affiliation
​AZIDUS Laboratories Ltd
Address
​AZIDUS Laboratories Ltd.,
No.23rd School Road, Rathinamangalam,
Behind Tagore Engg. College
(Via) Vandalur, Kelambakkam Road,
Chennai - 600 048
Kancheepuram TAMIL NADU 600 048 India
Phone
8056043873
Fax
Email
gunasakaran@azidus.com
Source of Monetary or Material Support
Mega Pharma S.A.
Ruta 101, Km. 23.500, Parque de las
Ciencias, Edificio Mega
Pharma, Piso 3, 14000 Canelones, Uruguay
Primary Sponsor
Name
Mega Pharma SA
Address
Mega Pharma S.A.
Ruta 101, Km. 23.500, Parque de las Ciencias,
Edificio Mega Pharma, Piso 3, 14000 Canelones, Uruguay
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Azidus Laboratories Limited
No 23, School Road, Rathnamangalam,
Chennai – 600 048
Countries of Recruitment
India
Sites of Study
No of Sites = 2
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr krishna Kumar Rathnam
Meenakshi Mission Hospital & Research Centre
Meenakshi Mission Hospital & Research Centre
Lake Area, Melur Road
Madurai - 625107 Madurai TAMIL NADU
04524263000
kkrathnam@gmail.com
Dr K C Lakshmiah
Srinivasam Cancer Care Multi Specialty Hospital India PVT LTD
Srinivasam Cancer Care Multi Specialty Hospital India PVT LTD
#36, 1st A Main, 5th Cross (Nethravathi Street), Maruthi Nagar, Nagarbhavi Main Road, Bangalore - 5600072 Bangalore KARNATAKA
09448055949
kcluck@gmail.com
Details of Ethics Committee
No of Ethics Committees= 2
Name of Committee
Approval Status
Institutional Ethics Committee
Submittted/Under Review
Srinivasam Cancer Care Multi Specialty Hospital Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Not Applicable
Health Condition / Problems Studied
Health Type
Condition
Patients
Metastatic cancer patients,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Capecitabine tablets 500 m
Capecitabine tablets 500 mg of Mega Pharma S.A.
Chile
Comparator Agent
Xeloda®
Capecitabine tablets 500 mg of Roche
Inclusion Criteria
Age From
18.00 Year(s)
Age To
60.00 Year(s)
Gender
Both
Details
Patients of 18 to 60 years of age (both years inclusive) with established cases of cancer, who are already receiving a stable twice-daily dosing regimen in multiples of 500 mg tablet (i.e., twice daily, equivalent to 2500 mg/m2 total daily dose, for 2 weeks followed by a 1 week rest period given as 3 week cycles) as prescribed by the reference product label.
Patients whose body surface area is ≤ 1.25 m2, between 1.52 – 1.65 m2, between 1.92 – 2.05 m2 & dose is to be given in multiples of 500 mg tablet
Subjects who have no evidence of underlying disease (except Dukes’ C colon cancer/ metastatic colorectal carcinoma/ metastatic breast cancer) during screening medical history and whose physical examination is performed within 21 days prior to commencement of the study.
Patients who are taking Capecitabine as a single agent for adjuvant treatment for Dukes’ C colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferre
Patients who are taking Capecitabine as first-line treatment for metastatic colorectal carcinoma when treatment with fluoropyrimidine therapy alone is preferred.
Patients who are taking Capecitabine for the treatment of metastatic breast cancer resistant to both paclitaxel and an anthracycline containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated, eg, patients who have received cumulative doses of 400 mg/m2 of doxorubicin or doxorubicin equivalents. (Only capecitabine as chemotherapeutic agent).
Patients should not take any adjuvant chemotherapeutic agent except capecitabine throughout the study and 4 weeks before the study.
Patients whose life expectancy of greater than or equal to 6 months.
Patients having histologically proven Cancer.
Patients having no brain metastasis.
 Patients with Performance ≤ 2 on the ECOG performance scale.
Subjects whose screening laboratory values are within normal limits or considered by the
Investigator/sub-Investigator to be of no clinical significance. Specifically, System Lab value ANC ≥ 1.5 × 103 /μl, Hb ≥ 10.0 g/dL, Platelets ≥ 1 lac/μl, Bilirubin ≤ 1.5 mg/dL, AST & ALT ≤ 2
x Upper Normal Limit or ≤ 5 × Upper Normal Limit (for liver mets)
Male Subjects must agree to comply with two highly effective contraceptive methods comprisinga barrier method (condom or occlusive cap plus spermicidal) for up to the last drug administration,and refrain from fathering a child for at least two (2) weeks following the last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception.
Female Subjects of child bearing potential practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as condoms, foams, jellies, diaphragm,intrauterine device (IUD), or abstinence or Postmenopausal for at least 1 year or
Surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy has been performed on the subject)
ExclusionCriteria
Details
Allergy or Significant history of hypersensitivity or idiosyncratic reactions to Capecitabine and/or any related compounds etc.
Cancer patients with a prior history of coronary artery disease, receiving concomitant therapy of
warfarin.
Cancer patients with a history of dihydropyrimidine dehydrogenase deficiency.
Presence of infections which reduce life expectancy.
Alcohol dependence, alcohol abuse or drug abuse or addiction with any recreational drug within
past one year.
Undergoing concomitant oncologic treatment.
Smoking (≥ 10 cigarettes/day) or consumption of tobacco products (≥ 4 chews/day).
History of difficulty in swallowing or coming for follow up.
Clinically significant illness (except Dukes’ C colon cancer/ metastatic colorectal
carcinoma/metastatic breast cancer) within 4 weeks before the start of the study.
Subjects who have been on an abnormal diet (for whatever the reason) during the four weeks
preceding the study.
Female subject who is pregnant, lactating or likely to become pregnant or have a positive
pregnancy test at screening and prior to check in.
Positive result to HIV, HCV, RPR and HbsAg.
Use of enzyme-modifying drugs (like Phenytoin, Carbamazepine, Barbiturates, Gresiofulvine) in
the previous 30 days before day 1 of this study.
Abnormal 12 lead ECG, X-ray.
Donation of 350 mL or more of blood in the previous 90 days before day 1 of this study. Participation in another clinical trial within the preceding 90 days of study starts.
Subjects who have:
Systolic blood pressure less than 90 mm of Hg or more than 140 mm of Hg
Diastolic blood pressure less than 60 mm of Hg or more than 90 mm of Hg. Minor
deviations (2-4mm Hg) at check-in may be acceptable at the discretion of the investigator.
Pulse rate below 60/min or above 100/min.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence between the test and reference formulations
To assess the bioequivalence between the test and reference formulations
Secondary Outcome
Outcome
TimePoints
To Assess the safety
Screening and Post Study
Target Sample Size
Total Sample Size="42" Sample Size from India="42" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
05/10/2017
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
None
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
An open label, balanced, randomized, two treatment, three
sequence, three period, single dose, Semi replicate, cross over, bioequivalence
study of Capecitabine tablets 500 mg of Mega Pharma S.A. Chile and Xeloda®
(Capecitabine) tablets 500 mg of Roche in metastatic cancer patients under fed
conditions.
Test Product-T : Capecitabine tablets 500 mg of Mega Pharma
S.A. Chile Reference Product-R : Xeloda® (Capecitabine) tablets 500 mg of Roche
Objective : To assess the bioequivalence between the test
and reference formulations.
Study design : An open label, balanced, randomized, two
treatment, three sequence, three period, single dose, Semi replicate, cross
over, bioequivalence study
Number of Subjects : Metastatic cancer patients who are
already receiving a stable twice-daily dosing regimen (i.e. 1250 mg/m2 , twice
daily, equivalent to 2500 mg/m2 total daily dose, for 2 weeks followed by a 1
week rest period given as 3 week cycles) shall be recruited in order to
complete the study with at least 42 patients. These patients shall be dosed in
Gi, i= 1, 2, 3... Clinical groups.
Type of study : Fed
Number of periods : 03
Washout period : The test and reference products will be
dosed on three consecutive days. Since the patients are on a twice daily dosing
regimen, there will be ~12 hours interval between the evening dosing in each
period and subsequent morning dosing. Subjects will be housed continuously for
both the periods since the dosing will be done with 24 hours interval between
each dose.
Fasting criteria : Minimum 08 hours fasting prior to high
fat high calorie breakfast and 04 hours post dose.
Water restriction : 01 hour pre-dose and 01 hour post-dose
Drug Administration :
In each of the periods, patients will receive tablets (as multiples of the 500 mg
tablet) of test or reference product of Capecitabine 500 mg tablet as per their
BSA (Body surface Area), using Mosteller formula. The tablets will be given
with 200 ml (± 2 ml) of water at ambient temperature, 30 minutes after
administration of high calorie high fat breakfast in the morning on Day 1
(period I), Day 2 (period II) and Day 3 (period III) of the treatment cycle,
after an overnight fasting of 08 hours (for each day) as per the randomization
schedule. Dosing will be done by trained person under the supervision of
investigator. After dosing, mouth check will be done to assess dosing
compliance. Similarly on day 1 (period I), day 2 (period II), and Day 3 (Period
III) evening dose of Capecitabine 500mg tablets (marketed product) will be
administered. For evening dose, the patients shall receive their usual dose of
capecitabine tablet as per their current dosing regimen.
Postural restrictions : Subjects will be administered with
study medications in sitting posture. Subjects will remain seated for 04 hours
after dosing. During this period, the subjects can be seated or ambulatory.
Clinical confinement : From at least 12.00 hours prior to
drug administration in Day 1 and until 12.00 hours post dosing in Day 3.
Safety assessment : Vital signs measurement and subject
well-being assessment will be done during subject check-in, housing and during
check out.
Laboratory
assessments : Screening – Hematology, Biochemistry, Serology, Urine analysis,
ECG, Chest X ray, Serum pregnancy test (for female volunteers). Check-In:
Alcohol breath analysis, urine drugs of abuse and urine pregnancy test (for
female volunteers)
Post study safety
analysis (At the end of study) – Hematology and biochemistry and Serum
pregnancy test (for female volunteers)
Sampling Schedule in
each period : 00.00 (Pre-dose), 00.17, 00.33, 00.50, 00.67, 00.83, 01.00,
01.25, 01.50, 01.75, 02.00, 02.33, 02.67, 03.00, 03.33, 03.67, 04.00, 04.50,
05.00, 06.00, 08.00 and 10.00 hours post-dose (Total of 22 samples - 3 ml
each). All the samples will be collected inside the clinic.
Total amount of blood draw : The total volume of blood draw
from each subject during the study will not exceed 245.0 ml.
Analytes : Capecitabine in plasma.
Bio-analytical procedure : A validated LC-MS/MS
bio-analytical method will be used for estimation of Capecitabine in plasma.
Pharmacokinetic
analysis and parameters : Pharmacokinetic analysis will be done using Phoenix®
WinNonlin v 7.0. Primary PK parameters: Cmax, AUC0-t and AUC0-∞ Secondary PK
parameters: Tmax, VD, CL, T½, Kel and AUC0-t / AUC0-∞ X 100
Statistical analysis : Statistical analysis will be
performed on the pharmacokinetic parameters using SAS® v 9.4. Statistical
analysis will be performed for the first 12 subjects. Based on the outcome of
the study results, the remaining subjects will be recruited and dosed.