CTRI/2021/09/036815 [Registered on: 24/09/2021] Trial Registered Prospectively
Last Modified On:
21/02/2023
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A Bioequivalence Study of Capecitabine 500 mg with Xeloda® 500 mg in Adult Cancer Patients Under Fed Condition.
Scientific Title of Study
A randomized, Open-label, Single Dose, Two Treatment, Three-Period, Three-Sequence, Partial Replicate, Crossover, Multicentre, Bioequivalence Study of Capecitabine 500 mg Tablets (Manufactured by SP Accure Labs Pvt. Ltd., India) with Xeloda® (Capecitabine 500 mg Tablets Distributed Roche Registration GmbH) in Adult Cancer Patients Under Fed Condition.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
01/CAP/SPAL/2020 Version No 1.0 dated15/JUN/2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Pranjal Ausekar
Designation
Head-Operations & Project Management
Affiliation
Ardent Clinical Research Services
Address
Office 304 & 305 Level 3, Nyati unitree Pune-Nagar Road, Yerwada, Pune Pune MAHARASHTRA 411006 India
Phone
7507779562
Fax
-
Email
pranjal@ardent-cro.com
Details of Contact Person Scientific Query
Name
Dr Yaswanth Allamneni
Designation
Manager R & D
Affiliation
SP Accure Labt Pvt. Ltd.
Address
Plot. No.12, Biotech Park. Phase II, Lalgadi Malakpet, Shamirpet, Medchal - Malkajgiri, Telangana, India Hyderabad TELANGANA 500101 India
Phone
8418663214
Fax
-
Email
yaswanth@spaccurelabs.com
Details of Contact Person Public Query
Name
Pranjal Ausekar
Designation
Head-Operations & Project Management
Affiliation
Ardent Clinical Research Services
Address
Office 304 & 305 Level 3, Nyati unitree Pune-Nagar Road, Yerwada, Pune Pune MAHARASHTRA 411006 India
Phone
7507779562
Fax
-
Email
pranjal@ardent-cro.com
Source of Monetary or Material Support
SP Accure Labs Private Limited, Plot. No.12, Biotech Park, Phase II, Lalgadi Malakpet, Shamirpet, Medchal - Malkajgiri, Telangana, India - 500101
Primary Sponsor
Name
SP Accure Labs Pvt Ltd
Address
Plot. No.12, Biotech Park, Phase II, Lalgadi Malakpet, Shamirpet, Medchal - Malkajgiri, Telangana, India 500101
IEC of Dr. VVP Foundations Medical College & Hospital, Ahmednagar
Approved
Institutional Ethics Committe MNJ Institute of Oncology and Regional Cancer Centree
Approved
Institutional Ethics Committee Dr RMLIMS
Approved
Institutional Ethics Committee Erode Cancer Centre
Approved
Institutional Ethics committee of Meenakshi mission hospital and research centre
Approved
Institutional Ethics Committee, KLE University
Submittted/Under Review
Shri Durgamba Independant EC
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: R971||Elevated cancer antigen 125 [CA 125],
Intervention / Comparator Agent
Type
Name
Details
Intervention
Capecitabine 500mg
Capecitabine by SP Accure Labs Pvt. Ltd. India.is a generic version of Capecitabine.
Capecitabine 500 mg tablets manufactured by SP Accure Labs Pvt. Ltd. India for oral administration (dose: multiples of 500 mg tablets) under fed condition. Single oral dose(1250mg/m2
) will be given in each period.
Comparator Agent
Xeloda 500mg
Xeloda® distributed by Roche Registration GmbH. for oral administration (dose: multiples of 500 mg tablets) under fed condition. Single oral dose (1250mg/m2) will be given in each period.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1.Males or non-pregnant or non-lactating females of age between 18 to 65 years (both inclusive).
2.Patients in whom capecitabine therapy is indicated
i.Dukes’ C colon cancer: Single agent as adjuvant therapy; or
ii.Metastatic colorectal cancer: First line as monotherapy when treatment with fluoropyrimidine therapy alone is preferred; or
iii.Metastatic Breast Cancer: As monotherapy in patients resistant to both paclitaxel and an anthracycline containing regimen.
3.Patients already receiving a stable twice-daily dosing regimen of capecitabine (i.e. 1250 mg/m2, twice daily, equivalent to 2500 mg/m2 total daily dose, for two-weeks followed by a one-week rest period given as three-week cycles).
4.Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
5.Patients with life expectancy of at least 3 months.
6.Adequate cardiac function [left ventricular ejection fraction (LVEF) ≥ 50%].
7.Patient with adequate ÂBone marrow (ANC ≥ 1500/mm3, Platelet count ≥ 100,000/mm3, Hemoglobin ≥ 9.0 g/dL); Renal (Serum Creatinine ≤ 1.5 times ULN and creatinine clearance ≥ 51 to 80 mL/min [Cockroft and Gault]) and Hepatic function (Bilirubin ≤ 1.5 times ULN, ALT/AST ≤ 3 times ULN (≤ 5 x ULN if liver metastases present)).
8.Patients should be non-smokers.
9.Patient willing and able to give written informed consent for participation in the study and comply with the study protocol.
10.No persistent clinically significant toxicities from prior medications at screening.
11.Females of child-bearing potential must agree to use an acceptable method of birth control such as sexual abstinence or at least reliable modes of contraception from screening until 3 months after last dose of study drug.
[Note: Use of hormonal contraception (pills/hormonal intrauterine device etc,) is not allowed].
OR Post-menopausal females defined as at least 12 consecutive months with no menses without an alternative medical cause.
OR Surgically sterilized females with documented evidence of hysterectomy/bilateral salpingectomy/bilateral oophorectomy.
12.Male patient must agree to use an acceptable method of birth control such as sexual abstinence or barrier method of contraception (i.e. condom) from screening until 3 months after last dose of study drug. Subject agrees to accept the risk that pregnancy in female partner could still result despite using birth control devices.
13.Cancer patients should preferably be on monotherapy. However, cancer patients receiving concomitant drug(s) are allowed to participate, provided:
Â-The concomitant medication is the same for all the study period and clearly documented.
Â-Patients do not require any change in their concurrent medications during the study period.
ExclusionCriteria
Details
1.Patients with known hypersensitivity to capecitabie or to any of its components of formulation or 5-fluorouracil.
2.Patients with known DPD (Dihydro pyrimidine Dehydrogenase) deficiency.
3.Prior unanticipated severe reaction to Capecitabine or metabolites and to fluoropyrimidine therapy.
4.Patients with a prior history of coronary artery disease.
5.Patients who are on oral-coumarin derivative anticoagulants such as warfarin or phenprocoumon at the time of screening or anticipated use of these drugs during the study period. [If the subject was on any of these drugs before screening, a wash out period of at least 5 half-lives must have elapsed since the last dose of such drug.]
6.Patients receiving concomitant therapy of Phenytoin, Leucovorin, and CYP2C9 substrates at the time of screening or anticipated use of these drugs during the study period. [If the subject was on any of these drugs before screening, a wash out period of at least 5 half-lives must have elapsed since the last dose of such drug.] Presence of active infections.
7.Patients with known brain metastasis.
8.Pre-existing motor or sensory neurotoxicity of severity ≥ 2 by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) criteria.
9.Use of any recreational drugs or history of drug addiction.
10.Have a history of alcohol or drug-dependence as per DSM-IV criteria during the 6-month period immediately prior to Screening.
11.Consumption of grapefruit, grapefruit-like or grapefruit containing products within 7 days prior to study drug administration.
12.Use of enzyme modifying drugs within 30 days prior to study drug administration. They can be allowed depending on Principal Investigator’s discretion if they are kept constant in the last 30 days and are expected to remain constant during the study period.
13.Major surgery to the gastrointestinal tract, liver or kidney within 3 months prior to study entry which may affect the pharmacokinetics of capecitabine.
14.History of difficulty in swallowing, or any gastrointestinal disease e.g. ulcerative colitis, ulcerative stomatitis, malabsorption syndrome and/or lack of physical integrity of the upper intestinal tract which could affect drug absorption.
15.History or presence of cardiac disease including myocardial infarction, unstable angina, coronary artery disease, heart failure, dysrhythmias, cardiomyopathy, significant pericardial disease or any other cardiac illness that could affect patient safety.
16. Electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
17.History or evidence of uncontrolled coagulopathy.
18.Patients with severe hepatic or renal impairment.
19.Patient having abnormal serum calcium level at screening visit which as judged by Investigator could lead to safety risk to the patient upon participation in the trial or could interfere with the conduct of the trial.
20.Patients who have had experienced a severe mucocutaneous reaction during prior capecitabine treatment.
21.History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venepuncture or patients who have bled more than 300 mL in the past 3 months.
22.Participation in any clinical trial of investigational drugs or devices in the past 3 months.
23.Any significant disease or condition of haemopoietic, gastrointestinal, renal, hepatic, cardiovascular, respiratory, central nervous system, diabetes, psychosis or any other body system which might compromise patient safety or affect study results.
24.Patients with positive alcohol breath test or positive urine screen test for drugs of abuse (Amphetamines, Morphine, Benzodiazepines, Marijuana, Cocaine and Barbiturates) at Period I hospitalization.
25.A positive screen test for HIV 1 and 2, or Hepatitis B (HBsAg) or Hepatitis C (HCV) virus.
26.History of allergy to heparin or any food allergy that in the opinion of the Investigator could contraindicate the patient’s participation in study.
27.Any other condition that in the investigator’s judgment, might compromise patient safety or affect study results.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Other
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
• To demonstrate the bioequivalence between Test product capecitabine 500 mg tablets (manufactured by SP Accure labs Pvt. Ltd., India) and Reference product Xeloda® (capecitabine 500 mg tablets).
i. Bioequivalence of two formulations (Test vs Reference) in relation to the
o Rate of absorption
o Extent of absorption
ii. Pharmacokinetic parameters: Cmax and AUC0-t.
Secondary Outcome
Outcome
TimePoints
•To monitor safety.
•To collect other pharmacokinetic data.
i.Adverse events, laboratory abnormalities will be monitored for safety.
ii.Assessment of the other pharmacokinetic parameters: AUC0-∞, Tmax, Kel, t1/2, AUC extrapolated %.
Target Sample Size
Total Sample Size="72" Sample Size from India="72" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="33"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The present study aims to determine bioequivalence of test capecitabine 500 mg tablets (single dose given will be multiples of 500mg tablets as per body surface area) with the marketed Xeloda® (Capecitabine 500 mg tablets) distributed by Roche Registration GmbH.. The patients will continue to receive the total calculated dose as per the prescribing physician by making up the dose using the standard capecitabine tablets taken by the patient in the evening dose of the day. The strength of the investigational product was determined to derive better pharmacokinetic profile and minimize safety concerns. Total 72 patients on stable dose of capecitabine 500mg wil be enroled. Patients with Metastatic colorectal cancer, colon cancer and breast cancer will be screened [-10 day to -1 day]. Patients will be hospitalized on day 0. Fasting period of 10 hrs from hospitalization till dosing. On day 1 patients will be given high fat and high calorie breakfast 30 min before dosing. Water will be restricted 1 hr before and after dosing.The drug product will be administered with 200 mL of water. Investigational products (Test or Reference) must be swallowed whole and must not be chewed, crushed or divided. This activity will be followed by mouth and hand check of the patients to assess compliance to dosing.The dose will be calculated based upon body surface area of patients. The recommended dose of capecitabine is 1250 mg/m2 administered orally twice daily (equivalent to 2500 mg/m2 total daily dose). The patients will be administered either the reference drug or the test drug only as the first morning dose.Sampling time points will be as below; In each period, a total of 15 blood samples (5 mL each) will be collected for PK analysis. The first sample will be collected within 5 minutes prior to drug administration (0.00 hour). Post dose samples will be collected at 10 mins, 20 mins, 30 mins, 45 mins, 1.00 hr , 1.33 (80 mins), 1.67 (100 mins), 2.00 hrs, 2.50 (150 mins), 3.00 hrs, 4.00 hrs, 5.00 hrs, 6.00 hrs and 8.00 hours after dosing in each period. The post-dose samples will be collected within ± 2 minutes of scheduled time.The total volume collected per patient in this study will not exceed 260.5 ± 10 mL including 8 mL for screening tests, 5 mL for end of study tests and around 0.5 mL of ‘discarded’ anticoagulant mixed blood prior to each sampling i.e. total volume of discarded blood is approximately 22 mL.Blood Sampling : Blood samples will be drawn by an indwelling cannula placed in the forearm vein with the help of a disposable sterilized syringe or a fresh clean venepuncture using a disposable sterilized syringe and a needle if required. The blood samples will be collected in pre-labelled (mentioning study number, site number, patient number, period and sampling time point) K3EDTA tubes. The pre-dose blood sample will be collected within 5 minutes before dosing; post-dose samples will be collected within ± 2 minutes of scheduled time till the 8.00 hours. The time at which 5 mL of blood samples are collected will be recorded in the CRF. Blood samples after collection should be centrifuged in non-refrigerated centrifuge at 3000 rpm for10 minutes to separate plasma. The resulting plasma from each blood sample will be divided into two aliquots and stored in suitably pre labelled polypropylene tubes at -20 °C ± 10 °C or colder.