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

Not Applicable

Conditions: Health Condition 1: G35- Multiple sclerosis

Registration Number: CTRI/2024/03/063701

Lead Sponsor: Invitro Research Solutions Private Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Closed to Recruitment of Participants

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

1 Participant must sign an ICF indicating that the participant understands the purpose of, and procedures required for the study and in this protocol and is willing to participate in the study.

2 Man or woman participant must be greater than or equal to 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place), at the time of signing the informed consent.

3 Body weight greater than or equal to 40 Kg

4 Participants with relapsing forms of multiple sclerosis including relapsing-remitting disease and active secondary progressive disease as per McDonald’s criteria, who are eligible and planned

to receive for the first cycle of either first or second treatment course of oral cladribine tablet as per investigator judgement.

NOTE: If a participant is receiving their Second Course/First Cycle of oral cladribine under

current study, then it must be at least 43 weeks after the last dose of First Course/Second Cycle.

5 A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

a. Is not a woman of childbearing potential (WOCBP)

a. Is a WOCBP and agrees to remain on an acceptable contraceptive method that is highly

effective (with a failure rate of less than 1% per year), with low user dependency when used

consistently and correctly

b. during the intervention phase and for at least 6 months after the last dose of study

intervention and agrees not to donate eggs (ova, oocytes) for the purpose of

reproduction during the study and for a period of at least 6 months after the last dose

of study intervention. The investigator should evaluate the effectiveness and the

potential for contraceptive method failure (e.g., noncompliance, recently initiated) of

the contraceptive method in relationship to the first dose of study intervention.

c. A WOCBP must have a negative highly sensitive serum pregnancy test at screening

and urine pregnancy test before each dosing.

d. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum

pregnancy test is required. In such cases, the participant must be excluded from

participation if the serum pregnancy result is positive

The investigator is responsible for review of medical history, menstrual history, and recent

sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

6 Male participants are eligible to participate if they agree to the following during the intervention phase and for at least 6 months after the last dose of study intervention:

a. Must agree not to donate sperm for the purpose of reproduction

PLUS EITHER:

b. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent

on a long-term and persistent basis) and agree to remain abstinent

a. Must agree to use contraception /barrier as detailed below

b. A male participant must wear a condom when engaging in any activity that allows for

passage of ejaculate to another person.

c. Male participants should also be advised of the benefit for a female partner to use a

highly effective method of contraception as condom may break or leak when having

sexual intercourse

Exclusion Criteria

1 Documented medical history of uncontrolled, clinically significant intercurrent cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances or any other medical condition(s) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

2 Known allergies, hypersensitivity, or intolerance to any of the study interventions, or components/excipients thereof (refer to the US prescribing information of Mavenclad), or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.

3 Contraindications to the use of study intervention per latest US prescribing information of Mavenclad

4 Current unstable liver or biliary disease with Child-Pugh score less than 6 at screening visit.

5 Participant with clinically significant current cardiac conditions like serious cardiac arrhythmia not controlled by adequate medication, electrocardiographic evidence of acute ischemic abnormalities, or any other cardiac illness that could lead to a safety risk to the participant in the opinion of the investigator.

6 Positive for HIV, or positive Hepatitis C antibody test or Hepatitis B surface antigen test and/or core antibody test for IgG and/or IgM.

7 Evidence of active or latent tuberculosis (TB) as detected by local standard of practice such as imaging and/or positive QuantiFERON-TB Gold test.

8 Presence of any clinically significant active systemic bacterial, viral or fungal infections (acute or chronic) as assessed by investigator at randomization. Randomization can be delayed till resolution or control of infection as assessed by investigator allowing use of cladribine tablet.

9 Live or live-attenuated vaccine(s) within 6 weeks prior to randomization, or plans to receive such vaccines during the study. Participants must agree to avoid live or live-attenuated vaccine(s) after study till white blood cell counts are within normal limits.

10 Current evidence or history of malignancy within the past 3 years except for (a) basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of disease for 3 years; or (b) any malignancy which is considered cured with minimal risk of recurrence AND whose natural history or treatment does not have the potential as judged by the investigator to interfere with the safety of the study intervention are eligible for this study.

11 Participants with neurological findings consistent with progressive multifocal leukoencephalopathy (PML), or confirmed PML. Baseline MRI is required during screening period if not done in past 3 months prior to administration of study intervention if it is the participant’s first treatment course.

12 Received a study intervention or used an invasive investigational medical device within 30 days or 5 half-lives prior to randomization, whichever is longer.

13 Participant’s clinical condition would not be feasible for pharmacokinetic assessment as determined by investigator.

14 Unable to swallow solid, oral dosage forms whole with the aid of water (participants must not chew, divide, dissolve, or crush the study intervention)

Study & Design

Study Type: BA/BE

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Following primary pharmacokinetic parameters <br/ ><br>will be assessed: <br/ ><br>a. Cmax and AUC0-tTimepoint: After First Dose

Secondary Outcome Measures

Name	Time	Method
Following secondary pharmacokinetic <br/ ><br>parameters will be assessed: <br/ ><br>a. AUC0-8, Tmax, AUC_% Exp, R2 <br/ ><br>adjusted, ?z, <br/ ><br>t1/2Timepoint: After First Dose;Frequency and/or incidence of adverse <br/ ><br>events (AE) and Serious Adverse Events <br/ ><br>(SAE)Timepoint: For entire study