Bioequivalence study of Cladribine 10 mg tablet in highly active relapsing multiple sclerosis patients

Completed

Conditions: Multiple sclerosis,

Registration Number: CTRI/2021/09/036201

Lead Sponsor: Hikma Pharmaceuticals

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 MAVENCLADÂ® (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 MAVENCLADÂ® (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.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 40

Inclusion Criteria

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/mmÂ³ 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: â€¢be post-menopausal or surgically sterilized; or â€¢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.
â€¢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.

Exclusion Criteria

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.

Study & Design

Study Type: BA/BE

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the bioequivalence of Cladribine Tablets 10 mg manufactured by Arab Pharmaceutical Manufacturing Company, Jordan for Hikma Pharmaceuticals, Jordan (MAH) and MAVENCLADÂ® (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 Measures

Name	Time	Method
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

Trial Locations

Locations (13): Department of Neurology, Institute of Medical Science,
🇮🇳
Varanasi, UTTAR PRADESH, India
Dr Jivraj Mehta Smarak Health foundation bakeri medical research centre
🇮🇳
Ahmadabad, GUJARAT, India
Gleneagles Global Health City
🇮🇳
Chennai, TAMIL NADU, India
Lifepoint Multispeciality Hospital Pvt. Ltd
🇮🇳
Pune, MAHARASHTRA, India
Lotus Multispeciality Hospital
🇮🇳
Ahmadabad, GUJARAT, India
Medipoint Hospital Pvt. Ltd
🇮🇳
Pune, MAHARASHTRA, India
Nirmal Hospital Private Limited
🇮🇳
Surat, GUJARAT, India
Noble Hospital Private Limited
🇮🇳
Pune, MAHARASHTRA, India
Rajalakshmi Hospital & Research center
🇮🇳
Bangalore, KARNATAKA, India
Rukmani Birla Hospital
🇮🇳
Jaipur, RAJASTHAN, India
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Department of Neurology, Institute of Medical Science,
🇮🇳Varanasi, UTTAR PRADESH, India
DrDeepika Joshi
Principal investigator
9918978666
drdeepikajoshi73@gmail.com