CTRI/2021/09/036201 [Registered on: 03/09/2021] Trial Registered Prospectively
Last Modified On:
10/02/2023
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study of Cladribine 10 mg tablet in highly active relapsing multiple sclerosis patients
Scientific Title of Study
An Open-Label, Balanced, Randomized, Single-Dose, Two-Treatment, Two-Period, Two-Sequence, Two-Way Crossover, Oral Bioequivalence Study of Cladribine Tablets 10 mg manufactured by Arab Pharmaceutical Manufacturing Company, Jordan for Hikma Pharmaceuticals, Jordan (MAH) and MAVENCLAD® (Cladribine) Tablets 10 mg manufactured by NerPharMa S.R.L., Italy for Merck Europe B.V., Netherlands (MAH) in 40 adult patients with highly active relapsing multiple sclerosis (MS) under fasting conditions.
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Yogesh Patidar
Designation
Principal Investigator
Affiliation
Vijay Vallabh Hospital and Medical Research Centre
Address
Vijay Vallabh Hospital and Medical Research Centre
Neurology Department, Ground Floor, OPD No 5, Unit of Tirupati life care
Plot No.423
Tirupathi Nagar, Phase 1, Boling, Virar (West)
Mumbai MAHARASHTRA 401303 India
Phone
09820001622
Fax
7030333224
Email
dryogeshpatidarvvh@gmail.com
Details of Contact Person Scientific Query
Name
Dr Channabasavanna G Halasagi
Designation
Manager-Medical Affairs
Affiliation
Invitro Research Solutions Pvt. Ltd
Address
Invitro Research Solutions Pvt. Ltd, Clinical Development Department, Medical Monitoring Division, Room No 301, 3rd Floor No. 22 & 23, Kodigehalli Main Road, Sahakar Nagar Post, Hebbal.
Bangalore KARNATAKA 560092 India
Phone
9449236330
Fax
-
Email
channa@ivrs.org.in
Details of Contact Person Public Query
Name
Mr T Vijay Bhaskar
Designation
Director-Clinical Development
Affiliation
Invitro Research Solutions Pvt. Ltd
Address
Invitro Research Solutions Pvt. Ltd, Clinical Development Department, Clinical Operations Division, Room No 301, 3rd Floor No. 22 & 23, Kodigehalli Main Road, Sahakar Nagar Post, Hebbal.
Bangalore KARNATAKA 560092 India
Phone
6366575282
Fax
-
Email
vijay@ivrs.org.in
Source of Monetary or Material Support
Hikma Pharmaceuticals
Primary Sponsor
Name
Hikma Pharmaceuticals
Address
21 Saleem Bin All-Hareth street
Industrial Area
Bayader Wadi Al-Seer
P.O. Box 182400
11118 Amman-Jordan
Department of Neurology, Institute of Medical Science,
Department of Neurology,Banarus Hindu University, Varanasi, I.M.S, U.P 221005 Varanasi UTTAR PRADESH
9918978666
drdeepikajoshi73@gmail.com
Patel Bhagyadhan Arvindbhai
Dr Jivraj Mehta Smarak Health foundation bakeri medical research centre
Dr Jivraj Mehta Smarak Health foundation Bakeri medical research centre
Ratubhi Adani Arogyadhan Dr Jivraj Mehta Marg Ahmedabad Gujarat 380007
Ahmadabad GUJARAT
8980011822
bhagyadhan30@gmail.com
Dr Venkatraman Karthikeayan
Gleneagles Global Health City
No 439 Cheran Nagar Perumbakkam
chennai 600 100 Chennai TAMIL NADU
9597748201
venkatramankarthikeayan2@gmail.com
Dr Priyanka Walzade
Lifepoint Multispeciality Hospital Pvt. Ltd
Neurology Department, Clinical Research Division, 1st Floor, OPD 02, 145/1, Mumbai Bangalore Highway,
Near Hotel Sayaji, Wakad
Pune MAHARASHTRA
Vijay Vallabh Hospital and Medical Research Centre
Neurology Department, Research Division, Ground Floor, OPD No 05, Unit of Tirupati life care
Plot No.423
Tirupathi Nagar, Phase 1, Boling, Virar (West), Maharashtra 401303
Mumbai MAHARASHTRA
Reference products (R): MAVENCLAD® (Cladribine) Tablets 10 mg manufactured by NerPharMa S.R.L., Italy for Merck Europe B.V., Netherlands (MAH).
In each period, after overnight fasting of at least 8 hours, a single dose of either Test product (T) or Reference product (R) will be administered orally to the subjects as per the randomization schedule in sitting posture with about 240 mL of water at ambient temperature in the morning
Intervention
Test products (T): Cladribine Tablets 10 mg manufactured by Arab Pharmaceutical Manufacturing Company, Jordan for Hikma Pharmaceuticals, Jordan (MAH)
In each period, after overnight fasting of at least 8 hours, a single dose of either Test product (T) or Reference product (R) will be administered orally to the subjects as per the randomization schedule in sitting posture with about 240 mL of water at ambient temperature in the morning
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Adult patients who are diagnosed with highly active relapsing multiple sclerosis (MS) according to the McDonald criteria at the time of screening as per the principal investigator.
2. Male or female, between 18 and 65 years of age.
3. Weighed between 40-99 kilogram (kg).
4. Subject with Lymphocyte count normal as per lower limit of normal range (of the central laboratory) for Year 01 treatment and greater than 800 cells/mm³ for Year 02 treatment.
5. Has a physical condition which enable patients to be fit for a Pharmacokinetic sampling according to principal investigator evaluation.
6. If female, she must:
• be post-menopausal or surgically sterilized; or
• uses a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study and willing to continue the same for 6 months from the last dose.
• And be neither pregnant nor breast-feeding.
7. If male, he must be willing to use contraception to avoid pregnancies during the study and willing to continue the same for 6 months from the last dose.
8. Be willing and able to comply with study procedures for the duration of the study
9. Able to understand and willing to sign written informed consent form.
ExclusionCriteria
Details
1. Has significant leukopenia (white blood cell count less than 0.5 times the lower limit of normal of the central laboratory) within 28 days prior to Study Day 1.
2. Has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to Study Day 1.
3. Has compromised immune function or infection.
4. Has received cytokine-based therapy, intravenous immunoglobulin therapy, or plasmapheresis within 3 months prior to Study Day 1.
5. Has platelet and absolute neutrophil counts below the lower limit of normal range within 28 days prior to Study Day 1.
6. Has prior or current history of malignancy.
7. Has systemic disease that, in the opinion of the Investigator, might interfere with subject safety, compliance or evaluation of the condition under Study (for example, insulin-dependent diabetes, clinically significant cardiac disease, moderate or severe hepatic impairment, moderate or severe renal impairment (creatinine clearance <60 mL/min).
8. Has a psychiatric disorder that, in the opinion of the Investigator, was unstable or would preclude safe participation in the study.
9. Has allergy or hypersensitivity to gadolinium, to cladribine or any of its excipients.
10. Has used any investigational drug or experimental procedure within 6 months prior to Study Day 1.
11. Patients who has been vaccinated with any live or attenuated live vaccines within 4 to 6 weeks of screening.
12. Patients with a history of alcohol, found with current alcohol abuse based on Alcohol breath test and with history of drug abuse, found urinary screen test positive for drugs of abuse (Marijuana-THC, amphetamine-AMP, barbiturates-BAR, cocaine-COC, benzodiazepines-BZD and opiates-OPI).
13. Patients who are diagnosed to be HIV 1 and 2 or Hepatitis B (HBsAg) or Hepatitis C (HCV) virus or COVID 19 reactive/positive.
14. Patients who have a history or active Tuberculosis and patients who have no history of exposure to varicella zoster virus.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence of Cladribine Tablets 10 mg manufactured by Arab Pharmaceutical Manufacturing Company, Jordan for Hikma Pharmaceuticals, Jordan (MAH) and MAVENCLAD® (Cladribine) Tablets 10 mg manufactured by NerPharMa S.R.L., Italy for Merck Europe B.V., Netherlands (MAH), in 40 adult patients with highly active relapsing multiple sclerosis (MS) under fasting conditions
In each period, total of 19 (04 mL each) blood samples will be collected at 0.00 (pre-dose) and at 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post-dosing
Secondary Outcome
Outcome
TimePoints
To monitor the safety of patients.
Safety parameters like Physical examination, safety laboratory parameters assessment (screening, mid study safety and post study), adverse events, vital signs will be recorded in the study to monitor the safety throughout the study period
Target Sample Size
Total Sample Size="40" Sample Size from India="40" Final Enrollment numbers achieved (Total)= "40" Final Enrollment numbers achieved (India)="40"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is open-label, balanced, randomized, single-dose, two-treatment, two-period, two-sequence, two-way crossover, oral bioequivalence study of test product cladribine tablets 10 mg and reference product of MAVENCLAD® (Cladribine) Tablets 10 mg. Dose administration is divided into two periods for the administration of two treatments in cross over design. In each period, after overnight fasting of at least 8 hours, a single dose of either Test product (T) or Reference product (R) will be administered orally to the subjects as per the randomization schedule in sitting posture with about 240 mL of water at ambient temperature in the morning.
The Primary outcome is to assess the bioequivalence of Cladribine Tablets 10 mg and MAVENCLAD® (Cladribine) Tablets 10 mg in 40 adult patients with highly active relapsing multiple sclerosis (MS) under fasting conditions.
The secondary outcome is to monitor the safety of patients.