Study Title

An open label,  multi-center, single-arm treatment, clinical trial to determine the safety and efficacy of Muco-adhesive tablets with active ingredient sodium hyaluronate 0.5% manufactured by Tree of Life Pharma Ltd.in human adult, patients with Recurrent Aphthous Stomatitis (RAS).

Phase of development

Final formulation, clinical testing for registration

Investigational  MedicinalProducts

Test Product (T):      The product is a Muco-adhesive tablet with active Ingredient Sodium Hyaluronate 0.5% manufactured by Tree of Life Pharma Ltd.

Objectives

Primary Objective:

To determine theefficacy ofthe muco-adhesive tablet with active ingredient Sodium Hyaluronate 0.5%manufactured by Tree of Life Pharma Ltd.in Human Adult, Patients with Recurrent Aphthous stomatitis (RAS).

Secondary objective:

To determine the safety and tolerability of the muco-adhesive tablet with active ingredient Sodium Hyaluronate 0.5%manufactured by Tree of Life Pharma Ltd.in Human Adult, Patients with Recurrent Aphthous stomatitis (RAS).

Study Design

An open label, multi-center, single arm treatment, clinical trial in human adult,patient with Recurrent Aphthous Stomatitis (RAS).

Study population

40 generally healthy patients with Recurrent Aphthous Stomatitis (RAS) with ONLY 1 aphthous wound will be enrolled in the study.

Primary Enrollment criteria

Demographic data, medical and medication historyand this history includes duration, frequency of ulcer, physical examination includes size of ulcer, serology,biochemistry, Pain intensity scale(By Visual Analog Scale) and size of the ulcer and photography of the ulcerwill be performed prior to study enrolment as baseline.Diagnosis of Aphthous stomatitis will be made prior to study enrolment.

Study duration

10 days

Duration will be from enrolment of the patient to until the visit completion day.The study treatment duration is 03 Days / 07-10 days for each patient.

Dose and Mode of Administration

The product is a muco-adhesive tablet with active ingredient sodium hyaluronate 0.5%. One tablet will be attached to the Aphthous ulcer according to the instructions and the patient will be instructed to use 2 tablets per day for 3 days, one tablet every 12 hours.

The 1^st dose will be applied in the clinical facility under the supervision of investigators (Daily doses till next visit will be dispensed and handed over to the patients). From the second dose onwards, patients will be instructed to use the products and apply it on their own. The patients will have more tablets than needed for the treatment in case the patient is having trouble adhering the tablets themselves. In any case the patient will not use more than 5 tablets of top of the first one used by the investigator (total of 6)

The product will firmly stick to the wound and within 4 hours it will becompletely dissolved. The patient will then be instructed to stick another muco-adhesive tablet after 12 hours from the first moment of the attachment of the first tablet.

Evaluation Schedule

Totally 04 visits.

·      Visit 01:Screening and enrollment (Day 01) and adhering the first tablet.

·      Visit 02: On therapy Visit (Day 03) – after the last tablet has been dissolved.

·      Visit 03: Follow up visit (Day 07)

·      Visit 04: End of study visit (Day 10)

Patients Safety Measures

·      Biochemistry and serology will be done on the day of screening.

·      At every visit, blood Pressure, radial pulse rate, oral temperature and wellbeing status will be enquired and recorded.

·      Monitoring of healing will be monitored on visits 2, 3 and 4 and photographing the area on each visit.

·      Another question that would be asked daily:"is the pain stronger or weaker than before the treatment?" This question will be asked on day 02, day 04, through telephone.

·      Monitoring for adverse events will be done throughout the study period.

Efficacy assessment

Primary Efficacy evaluations will be done as follows:

·       On the first visit – adhering the tablet and a VAS questionnaire will be performed before the tablet (baseline) and immediately after sticking the tablets on the aphthous ulcer.

·       On Therapy Visit – Visit 02 –72 hours (Day-03)

·       Follow up visit – Visit 03 (Day – 07)

·       End of  Study -- Visit 04 (Day – 10)

Any adverse events would be noted during this evaluation period.

Clinical endpoint

Primary end points

·      To determine the mean of aphthous ulcer size reduction (Days required to heal the ulcer) on Day 03, Day 07 andDay 10.

·      Pain intensity reduction using a Pain intensity Scale through VAS (Visual Analogue Scale) on Day 1 before the treatment and after the first tablet, Day 03 or Day 07 or day 10

·      Another question that would be asked daily:"is the pain stronger or weaker than before the treatment?" This question will be asked on day 02, day 04, through telephone

Secondary end points

·      The assessment of Quality of Life by using a questionnaire subdivided into 3 domains:

-Functional level

-Medication limitation

-Treatment limitation of subjects  during treatment period

·       Monitoring of Adverse event throughout the study period.

Ethical Issues

The study will be conducted as per the pertinent requirements of the Ethical guidelines for biomedical research on human participants, ICMR (2017), ICH (Step 5) ’Guidance on Good Clinical Practice’, ’Good Laboratory Practice’, ‘Good Clinical Practices for Clinical Research in India’ Guidelines, Good Clinical Laboratory Practice (GCLP), Declaration of Helsinki (Fortaleza, October 2013), New Drugs and Clinical Trials Rules 2019 G.S.R. 227(E) dated 19 Mar 2019 and applicable regulatory requirements.