CTRI/2011/11/002171 [Registered on: 25/11/2011] Trial Registered Prospectively
Last Modified On:
23/05/2012
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A Clinical trial intended to compare two formulations of Capecitabine tablets, in patients with Breast Cancer or Colorectal Cancer.
Scientific Title of Study
Single-Dose Fed Bioequivalence Study of Capecitabine Tablets (500 mg; Mylan) to Xeloda® Tablets (500 mg; Genentech) in Adult Cancer Patients with Metastatic Breast Cancer, Duke’s C Colon Cancer or Metastatic Colorectal Cancer.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CAPE 11121
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Charu Gautam
Designation
Director- Global Clinical Operations
Affiliation
BA Research India Limited
Address
BA Research India Limited
Sigma-1 Corporate, Off S.G.Highway, Bodakdev, Ahmedabad, Gujarat. BA House, Opp. Pushparaj Tower, Near Judges Bungalow Road, Bodakdev, Ahmedabad, Gujarat Ahmadabad GUJARAT 380054. India
Phone
07966135655
Fax
07966135641
Email
charu@baresearchindia.com
Details of Contact Person Scientific Query
Name
Dr Charu Gautam
Designation
Director- Global Clinical Operations
Affiliation
BA Research India Limited
Address
BA Research India Limited
Sigma-1 Corporate, Off S.G.Highway, Bodakdev, Ahmedabad, Gujarat. BA House, Opp. Pushparaj Tower, Near Judges Bungalow Road, Bodakdev, Ahmedabad, Gujarat Ahmadabad GUJARAT 380054. India
Phone
07966135655
Fax
07966135641
Email
charu@baresearchindia.com
Details of Contact Person Public Query
Name
Dr Charu Gautam
Designation
Director- Global Clinical Operations
Affiliation
BA Research India Limited
Address
BA Research India Limited
Sigma-1 Corporate, Off S.G.Highway, Bodakdev, Ahmedabad, Gujarat. BA House, Opp. Pushparaj Tower, Near Judges Bungalow Road, Bodakdev, Ahmedabad, Gujarat Ahmadabad GUJARAT 380054. India
Phone
07966135655
Fax
07966135641
Email
charu@baresearchindia.com
Source of Monetary or Material Support
Mylan Pharmaceuticals Inc
Primary Sponsor
Name
Mylan Pharmaceuticals Inc
Address
Mylan Pharmaceuticals Inc.
3711 Collins Ferry Road
Morgantown, WV 26505, USA
Tel: (304) 554-6718 Fax: (304) 554-6483
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
BA Research India Ltd
BA House, Opposite Pushparaj Towers
Nr. Judges Bungalows
Bodakdev, Ahmedabad - 380 054
Gujarat, India
Countries of Recruitment
India
Sites of Study
No of Sites = 10
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Tanveer Maksud
Bharat Cancer Hospital & Research Institute
Dept. of Medical Oncology, Surat-bardoli Road,Saroli-394 211 Surat Surat GUJARAT
9909918887
abu.ansar@yahoo.co.in
Dr Ajay Mehta
Central India Cancer Research Institute,
Dept. of Surgical Oncology, 11, Shankar Nagar , West High Court Road , Nagpur- , Maharashtra Nagpur MAHARASHTRA
09823190192
ajayonco@hotmail.com
Dr Rajanish Nagarkar
Curie Manavata Cancer Centre
Department of Radiation Oncology , Opp Hotel Sandeep, Mumbai Naka , Nasik Nashik MAHARASHTRA
9823061929
drrajnagarkar@yahoo.co.in
Dr G N Patel
Jeevandip Hospital,
Dept. of Surgical Oncology, AYUSH doctor house , 302, 3rd floor, Near Param Doctor House, Station to lal darwaja road, Near Resham Bhuvan , Surat Surat GUJARAT
09376913131
v_desai02@yahoo.com
Dr J K singh
Mahavir Cancer Sansthan,
Dept. of Radiation Oncology, Phulwarisharif Patna-801 505 Patna BIHAR
09431021001
drjksingh147@hotmail.com
Dr Kirushnakumar
Meenakshi Mission Hospital & Research Centre
Dept. of Radiation Oncology, Opp. Lake area, Melur Road, Madurai, Tamil Nadu Madurai TAMIL NADU
9787713004
drksku@yahoo.com
Dr Anup Majumdar
Nightingale Hospital
Dept. of Medical Oncology, 11 Shakespere Sarani, Kolkata Kolkata WEST BENGAL
9830152485
anup.majumdar@gmail.com
Dr Minish Jain
Noble Hospital
Dept. of Medical Oncology, Noble Hospital, 153, Magarpatta City Prad , Pune Pune MAHARASHTRA
9823133390
minishjain009@gmail.com
Dr C Haritha
Shree Krishna Hospital
DEPT. OF MEDICAL ONCOLOGY, M S PATEL CANCER CENTRE
SHREE KRISHNA HOSPITAL, GOKAL NAGAR, KARAMSAD, Anand Anand GUJARAT
9427042969
chiragp@charutarhealth.org
Dr Pradeep Shah
Shreyas Medical clinic and hospital
Dept. of Medical Oncology, 2 Premal appartment, GPO, Raopura, Vadodara - 390001, Gujarat Surat GUJARAT
Institutional ethics committee Nobel Hospital, Pune
Approved
Professional Ethics Committee, Manavata Clinical Research Insitute, Nashik
Approved
Research Independent Ethics Committee, Surat
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Metastatic Breast Cancer, Duke’s C Colon Cancer or Metastatic Colorectal Cancer,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Capecitabine Manufactured by Mylan Pharmaceutical Inc., USA
Each patient will receive a Capecitabine 1250 mg/m2 administered twice daily orally :BD (morning and evening; equivalent to 2500 mg/m2 total daily dose)for 14 days. The dose will be comprised of multiples of the 500 mg tablet
Comparator Agent
XELODA® (Capecitabine 500 mg) tablets.
XELODA® 500 mg tablets, Manufactured by Genentech US Inc. USA).Each patient will receive a Capecitabine 1250 mg/m2 administered twice daily orally :BD (morning and evening; equivalent to 2500 mg/m2 total daily dose)for 14 days. The dose will be comprised of multiples of the 500 mg tablet.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
1. Volunteers must be receiving stable doses of capecitabine (e.g. 2500 mg/m2/day in two divided dose) for the treatment of metastatic breast cancer (in combination with docetaxel), Dukes’ C colon cancer following complete resection, and metastatic colorectal carcinoma in combination with capecitabine (e.g. 2500 mg/m2/day in two divided doses).
a. Patients must have completed at least one 21-day cycle of capecitabine (i.e. 14 days of capecitabine and 7 days washout) at the dose to be utilized in this study.
b. The dose of capecitabine must be administered as a multiple of the intact, unbroken, 500 mg tablet.
2. Cancer patients with monotherapy are preferred. However, cancer patients receiving concomitant drug(s) are allowed to participate, provided:
a. The concomitant medication is the same during all study days. Each concurrent medication will be documented and clearly identified. Information recorded will include at least the following information: generic name, strength, dosing regimen, and time of dosing.
b. The subjects will follow the same dosing regimen for the concurrent medications for all dosing of the bioequivalent study.
c. Patients will not change their concurrent medications during the BE study.
d. Prior to inclusion of the subject into the study, a list of all concurrent medications will be provided to the sponsor for approval.
1. 3. Age: 18 – 80 years of age (inclusive)
2. 4. Sex: Females of non-childbearing potential and Males (with equal numbers of each sex, if possible).
a. Women will not be considered of childbearing potential if one of the following is reported and documented on the medical history:
i. postmenopausal with spontaneous amenorrhea for at least one (1) year, or
ii. bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or
iii. total hysterectomy and an absence of bleeding for at least 3 months.
b. Non-lactating (or not nursing)
5. Capable of informed consent.
6. Weight Restrictions:
a. At least 50 kg (110 lbs) for men and
b. At least 48 kg (106 lbs) for women
c. All subjects will have a Body Mass Index (BMI) less than or equal to 35 but greater than or equal to 19. BMI values should be rounded to the nearest integer (ex. 35.4 rounds down to 35, while 18.5 rounds up to 19).
7. Tobacco Use: Non-smokers to moderate-smokers (< 20 cigarettes per day) will be eligible to participate in this study.
8. All subjects should be judged by the principal or Medical Sub-Investigator physician listed on the Form FDA 1572 as normal and healthy during a pre-study medical evaluation performed within 28 days of the initial dose of study medication which will include:
a. Normal or non-clinically significant physical examination including vital signs (respiration rate, blood pressure, temperature and heart rate).
b. Within normal limits or non-clinically significant laboratory evaluation results, (unless otherwise noted in the exclusion criteria), for the following tests:
i. Serum Chemistries
ii. Hematology
iii. Urinalysis
c. negative Hepatitis B and Hepatitis C tests,
d. negative HIV test,
e. INR within normal range
f. normal or non-clinically significant 12-lead ECG
g. negative urine drug screen for all of the following compounds: amphetamines, barbiturates, benzodiazepines, cannabinoid, cocaine, methadone, opiates, and phencyclidine.
9. Additional tests and or examinations may be performed, if judged necessary by the Principal Investigator or Medical Sub-Investigator physician.
ExclusionCriteria
Details
Subject candidates must not be enrolled in the study if they meet any of the following criteria:
1. Institutionalized subjects will not be used.
2. Individuals with dihydropyrimidine dehydrogenase (DPD) deficiency.
3. Individuals with rapidly progressing disease, especially with visceral organ involvement.
4. Individuals requiring a change in dose or regimen of either capecitabine or had their dosing regimen altered within the previous 21 days.
5. Social Habits:
a. Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within the 48 hours prior to the initial dose of study medication.
b. Ingestion of any vitamins, food, or herbal supplement known to induce or inhibit hepatic enzyme activity within 7 days prior to the initial dose of study medication. Especially those known to inhibit or induce CYP3A4.
6. Medications:
a. Use of warfarin currently or within the last 3 months.
b. Use of any prescription or over-the-counter (OTC) medications within the 24 hours prior to the initial dose of study medication, except for any necessary medication for which dosing has been stabilized for a period of at least 21 days and is expected to remain stable for the entire study.
c. Use of any medication known to induce or inhibit hepatic enzyme activity within 28 days prior to the initial dose of study medication except for any necessary medication for which dosing has been stabilized for a period of at least 28 days and is expected to remain stable for the entire study.
7. Diseases:
a. History of unstable or clinically significant gastrointestinal disease, including a history of chronic diarrhea, inflammatory bowel disease, unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting). History of difficulties in swallowing.
b. ALT and AST greater than 2.5 times the upper limit of normal and/or total bilirubin greater than 2.5 times the upper limit of normal.
c. Patients with significant hepatic or renal dysfunction, or for whom the need for dose changes during the study can be anticipated.
d. Patients with a prolonged QT
e. Known history of prior tuberculosis infection, or any contact within the past 2 years with person with active tuberculosis.
f. History of moderate (30-50 mL/min creatinine clearance) or severe (≤ 30 mL/min creatinine clearance) renal disease.
g. History of unstable or clinically significant cardiovascular disease, hepatic, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic (including any history of seizure disorder), psychological, musculoskeletal disease or malignancies unless deemed not clinically significant by the Principal Investigator or Medical Sub-Investigator.
h. Acute illness at the time of either the pre-study medical evaluation or dosing.
8. Any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the subject form safely participating in the study.
9. Donation or loss of blood or plasma: 50 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medication.
10. Intolerance to venipuncture.
11. Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.
12. History of allergy or hypersensitivity to capecitabine, or other related products, or any of the inactive ingredients.
13. Consumption of grapefruit, grapefruit-like, or grapefruit containing products within 7 days of drug administration.
14. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Principal Investigator or Medical Sub-Investigator, could contraindicate the subject’s participation in this study.
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 characterize the pharmacokinetic profile of the sponsor’s test formulation (Capecitabine Tablets 500 mg, Manufactured by Mylan Pharmaceutical Inc., USA) relative to that of reference formulation (XELODA® 500 mg tablets, Manufactured by Genentech US Inc. USA) in patients of Metastatic Breast Cancer, Duke’s C Colon Cancer or Metastatic Colorectal Cancer under fed condition and to assess the bioequivalence.
NIL
Secondary Outcome
Outcome
TimePoints
To monitor the safety of the patients
Period one, two and three of the cycle
Target Sample Size
Total Sample Size="42" Sample Size from India="42" Final Enrollment numbers achieved (Total)= "" Final Enrollment numbers achieved (India)=""
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This study is a multi-center, open-label, single-dose, three-period, randomized, two-treatment, crossover study to investigate the bioequivalence of a single formulation of Mylan’s Capecitabine Tablets, 500 mg compared to the Genentech’s Xeloda® Tablets, 500 mg.
The single-dose pharmacokinetics of capecitabine will be characterized in forty-two (42) adult, male and not of childbearing potential female volunteers with metastatic breast cancer, Duke’s C colon cancer after complete resection, or metastatic colorectal cancer for whom the drug is indicated either alone or in combination with another drug.
Each patient will receive a capecitabine dose of 1250 mg/m2 dose in the morning under fed conditions.The dose will be comprised of multiples of the 500 mg tablet.In order to determine the pharmacokinetic parameter (CPEAK and AUC) intra-patient variability for Xeloda®, each patient will receive Xeloda® twice during the course of the study.
Subjects will be housed at least 10 hours prior to the first dose of investigational product until at least 12 hours after the final dose of investigational product.Blood samples (1×4 mL) will be collected in K2 EDTA tubes 30 minutes prior to drug dosing and 0.25, 0.50, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10hours post-dose. Patients will receive their regularly scheduled dose of capecitabine 12 hours after the morning dose of investigational product. Patients will receive a single dose of the test product and two doses of the reference product between Cycle Day 2 and Cycle Day 13 (inclusive) of a single treatment cycle.
In between investigational (test/reference) product administration, the patient will continue to receive their standard dosing regimen medication.
The collected blood samples will be cooled in an ice bath or sample cooling rack (e.g. Kryorack) and centrifuged under refrigeration as soon as possible.
Plasma will be extracted, divided into two (2) equal aliquots, and stored in suitably labeled tubes at −20°C ± 5°C or colder until shipment to the central storage site. For each subject the duration of the study will be 3 to 11 days.