Study Title:- A Multi-Centre, Randomized, Double Blind, Parallel-Group, Comparative Clinical Trial to evaluate the Safety and Clinical Equivalence of Generic Clotrimazole Troche/Lozenges USP, 10mg (manufactured by Unique Pharmaceutical Laboratories, India) to Clotrimazole Troche/Lozenges ® 10mg (Roxane Laboratories Inc., USA) in subjects with Oropharyngeal Candidiasis

Study Rationale: - Oropharyngeal Candidiasis is a mycosis (yeast/fungal infection) of Candida species on the mucous membranes of the mouth. Clotrimazole is a broad-spectrum antifungal agent which is fungistatic and fungicidal and has not shown any serious adverse events. Topical drugs show increased bioavailability. By administration of a topical alternative, the affected area can be treated directly in a manner which greatly minimizes the adverse effects associated with oral medications.  Hence, topical alternative minimizes the adverse events. Clotrimazole troche persists in the saliva at sufficient concentration for around 3 hours. This long term persistence of drug in saliva appears to be related to the slow release of clotrimazole from the oral mucosa to which the drug is apparently bound. Also, given as a troche, it may be the best choice nowadays owing to its high clinical success rate, safety, cost effectiveness, and high subject acceptability.

Primary Objective is to evaluate the clinical cure i.e. complete resolution of all signs and symptoms of Oropharyngeal Candidiasis, 7 days after the end of the therapy, (Day 21(+4)), which will be assessed using the Murray scale. According to the Murray Scale, lesion score 0 (0=none, 1=single, localized, 2=multiple, localized, 3=extensive, confluent) and symptom score 0 (0=absent, 1=mild, 2=moderate, 3=severe) will be considered as clinical cure 

Secondary Objective is to assess the mycological cure (negative culture and negative KOH for Candida species) and complete resolution of all signs and symptoms of Oropharyngeal Candidiasis at Day 15(+2). 

Sample Size: - 360 randomized, completed subjects in order to achieve at least 250 per-protocol (PP) subjects.

Study Design: - A Multi-Centre, Randomized, Double Blind, Parallel-Group, Comparative Clinical Trial. The subjects would be assigned to test product and reference product in the ratio of 1:1.

Arm A: Test Product: Clotrimazole troche/ lozenges USP, 10 mg (Unique Pharmaceutical Laboratories, India)

Arm B: Reference Product: Clotrimazole Troche/ Lozenges USP, 10 mg (Roxane Laboratories Inc., USA)

Duration of the Clinical Trial:- Total duration of the study will be approximately 5 months. After Randomization, the treatment will be for 14 consecutive days, and follow-up will be conducted on Day 8(+2), Day 15(+2) and Day 21(+4).

Statistical analysis: - Continuous data will be described using Mean, Standard Deviation, Median, Minimum and Maximum values. Categorical data will be described using counts and percentages. P value less than 0.05 will be considered as statistically significant.

The Per-Protocol population (PP) will include all randomized subjects who met all inclusion/exclusion criteria, had a positive baseline Candida culture, complied with minimum treatment course, returned to study site for primary end point assessment visit (Day 21 (± 4)) or discontinued from the study as treatment failure and did not have any protocol violations. This PP population will be used for efficacy analysis.

Efficacy: The efficacy evaluation will be calculated based on the primary and secondary endpoints of the study.

Safety: Safety will be evaluated by assessing laboratory parameters on visit 1 and visit 5 which includes (CBC, BSL (R), Blood urea and Serum creatinine) & LFT [T.Bil, ALKP, SGPT & SGOT]. Vital signs will be measured at all visits and will be used for safety assessment. Safety parameters will also be assessed by adverse event monitoring throughout the study.