Bioequivalence study ofCapecitabine tablets 500 mg

Recruiting

• Conditions: Metastatic cancer patients

• Registration Number: CTRI/2018/05/014342
• Lead Sponsor: Mega Pharma SA

Brief Summary

An open label, balanced, randomized, two treatment, threesequence, three period, single dose, Semi replicate, cross over, bioequivalencestudy of Capecitabine tablets 500 mg of Mega Pharma S.A. Chile and Xeloda®(Capecitabine) tablets 500 mg of Roche in metastatic cancer patients under fedconditions.

Test Product-T : Capecitabine tablets 500 mg of Mega PharmaS.A. Chile Reference Product-R : Xeloda® (Capecitabine) tablets 500 mg of Roche

Objective : To assess the bioequivalence between the testand reference formulations.

Study design : An open label, balanced, randomized, twotreatment, three sequence, three period, single dose, Semi replicate, crossover, bioequivalence study

Number of Subjects : Metastatic cancer patients who arealready receiving a stable twice-daily dosing regimen (i.e. 1250 mg/m2 , twicedaily, equivalent to 2500 mg/m2 total daily dose, for 2 weeks followed by a 1week rest period given as 3 week cycles) shall be recruited in order tocomplete the study with at least 42 patients. These patients shall be dosed inGi, i= 1, 2, 3... Clinical groups.

Type of study : FedNumber of periods : 03

Washout period : The test and reference products will bedosed on three consecutive days. Since the patients are on a twice daily dosingregimen, there will be ~12 hours interval between the evening dosing in eachperiod and subsequent morning dosing. Subjects will be housed continuously forboth the periods since the dosing will be done with 24 hours interval betweeneach dose.

Fasting criteria : Minimum 08 hours fasting prior to highfat 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 mgtablet) of test or reference product of Capecitabine 500 mg tablet as per theirBSA (Body surface Area), using Mosteller formula. The tablets will be givenwith 200 ml (± 2 ml) of water at ambient temperature, 30 minutes afteradministration 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 randomizationschedule. Dosing will be done by trained person under the supervision ofinvestigator. After dosing, mouth check will be done to assess dosingcompliance. Similarly on day 1 (period I), day 2 (period II), and Day 3 (PeriodIII) evening dose of Capecitabine 500mg tablets (marketed product) will beadministered. For evening dose, the patients shall receive their usual dose ofcapecitabine tablet as per their current dosing regimen.

Postural restrictions : Subjects will be administered withstudy medications in sitting posture. Subjects will remain seated for 04 hoursafter dosing. During this period, the subjects can be seated or ambulatory.

Clinical confinement : From at least 12.00 hours prior todrug administration in Day 1 and until 12.00 hours post dosing in Day 3.

Safety assessment : Vital signs measurement and subjectwell-being assessment will be done during subject check-in, housing and duringcheck out.

Laboratoryassessments : 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 (forfemale volunteers)

Post study safetyanalysis (At the end of study) – Hematology and biochemistry and Serumpregnancy test (for female volunteers)

Sampling Schedule ineach 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 mleach). All the samples will be collected inside the clinic.

Total amount of blood draw : The total volume of blood drawfrom each subject during the study will not exceed 245.0 ml.

Analytes : Capecitabine in plasma.

Bio-analytical procedure : A validated LC-MS/MSbio-analytical method will be used for estimation of Capecitabine in plasma.

Pharmacokineticanalysis and parameters : Pharmacokinetic analysis will be done using Phoenix®WinNonlin v 7.0. Primary PK parameters: Cmax, AUC0-t and AUC0-∞ Secondary PKparameters: Tmax, VD, CL, T½, Kel and AUC0-t / AUC0-∞ X 100

Statistical analysis : Statistical analysis will beperformed on the pharmacokinetic parameters using SAS® v 9.4. Statisticalanalysis will be performed for the first 12 subjects. Based on the outcome ofthe study results, the remaining subjects will be recruited and dosed.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-05-10
• Last Update Posted: 2018-05-31

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

• 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).

Exclusion Criteria

• Allergy or Significant history of hypersensitivity or idiosyncratic reactions to Capecitabine and/or any related compounds etc.
• Cardiovascular (including coronary artery disease), pulmonary, hepatic impairment, renal (including severe renal impairment), hematological (including leucopenia, thrombocytopenia), gastrointestinal, endocrine, immunologic, dermatologic, musculoskeletal, neurological, or psychiatric disease.
• 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.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the bioequivalence between the test and reference formulations	To assess the bioequivalence between the test and reference formulations

Secondary Outcome Measures

Name	Time	Method
To Assess the safety	Screening and Post Study

Trial Locations

Locations (2)

Meenakshi Mission Hospital & Research Centre; 🇮🇳 Madurai, TAMIL NADU, India

Srinivasam Cancer Care Multi Specialty Hospital India PVT LTD; 🇮🇳 Bangalore, KARNATAKA, India

Meenakshi Mission Hospital & Research Centre

🇮🇳Madurai, TAMIL NADU, India

Dr krishna Kumar Rathnam

Principal investigator

04524263000

kkrathnam@gmail.com