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Clinical Trial Results Synopsis Study Design Description Study Sponsor: Bayer Healthcare AG Study Number: 0410 Study Phase Official Study Title: Test Product N/A Therapeutic Area: Anti-Infective NCT00000000 Randomized, mycologically controlled comparative study to verify efficacy and tolerance of 3-day therapy with Clotrimazole (BAY B 5097) vaginal cream 2% in comparison with 6-day therapy with Clotrimazole (BAY B 5097) vaginal cream 1% in vaginal Candida infections Name of Test Product Name of Active Ingredient: Dose and Mode of Administration: Canesten (Clotrimazole, BAYB5097) Vaginal cream 2% bisphenyl-(2-chlorophenyl)-1-imidazolyl-methane (Clotrimazole) Vaginal application of one applicator full once daily for 3 days, delivering about 5 g at each application. Reference Therapy/Placebo Reference Therapy: Canesten (Clotrimazole, BAYB5097) vaginal cream 1% Dose and Mode of Administration: Vaginal application of one applicator full once daily for 6 days, delivering about 5 g at each application. Duration of Treatment: 3 days for Clotrimazole (BAY B 5097) 2% group Studied period: 6 days for Clotrimazole (BAY B 5097) 1% group Date of first subjects first visit: 01 Sep 1978 Date of last subjects last visit: 26 Jul 1979 Study Center(s): The study was conducted at a single site in Germany. Methodology: The study was set up as a randomized comparison of treatment, efficacy, and tolerance of a three-day treatment with Clotrimazole (BAY B 5097) vaginal cream 2% in comparison with a six-day treatment with Clotrimazole (BAY B 5097) vaginal cream 1%. The study was designed for a total of 100 mycologically confirmed vaginal yeast infection subjects, 50 in each treatment group. Indication/ Main Inclusion Criteria: The cream was applied intravaginally by means of applicators on 3 (2% cream) or 6 (1% cream) consecutive days. Assignment to the specific group (3-day 2% or 6-day 1% cream) followed the order of inclusion in the study. The therapeutic result was verified clinically and mycologically (native preparation and culture) 1 week and 4 weeks after the end of therapy. Indication: Vaginal Creams Vaginal Candida infections. Page 1 of 4
Study Objectives: Evaluation Criteria: Statistical Methods: Number of Subjects: Inclusion criteria: Positive Candida findings in the native preparation (budding cells, pseydomycelia) Confirmation of findings by cultural mycologic examination. Overall: To verify the efficacy and local tolerance of 3-day treatment with Clotrimazole (BAY B 5097) vaginal cream 2% compared to 6-day treatment with 1% Clotrimazole (BAY B 5097) vaginal cream. Primary: To verify the efficacy of 3-day treatment with Clotrimazole (BAY B 5097) vaginal cream 2% Efficacy (Primary): The result of the therapy was evaluated 1 and 4 weeks after the end of treatment, based on the results of the mycologic analysis (native and culture) and the clinical findings as regards to the symptoms of leukorrhea, itching, burning, and changes of the vaginal mucosa. Safety: Tolerance by the subject to the test drug Efficacy (Primary) - if applicable: Out of the two variables listed for findings, "native preparation" and "pseudomycelia", the latter is considered decisive for evaluation of the efficacy based on the native examination. Findings for the native preparation (pseudomycelia) and the culture were described in a 4-dimensional contingency table: Vulvitis, treatment, finding 1 week after end of therapy and finding 4 weeks after end of therapy. The overall course was described in a 3-dimensional contingency table: Vulvitis, treatment and finding on the 1st and 4th week. The findings from the overall course were summarized as follows: Finding 1st and 4th week negative, finding 1st week negative and 4th week positive, and finding 1st week positive. This scheme of evaluation was complemented with an exact 2- dimensional contingency table test without consideration of the interference factor vulvitis. Since taking the 4th week into account resulted in a somewhat greater loss of information compared to that when only the 1st follow-up examination was considered (data on some subjects were lacking for the 2nd followup), the therapeutic results (culture and native preparation) were processed 1 week after the end of treatment in additional 4-field tables of treatment and finding for comparison by the exact Fisher's test. Safety: Statistical analysis of safety was not planned. Planned: 100 subjects Enrolled: 101 subjects Page 2 of 4
Results Summary Subject Disposition and Baseline Excluded from Analysis: 12 subjects due to missing data Analyzed: 89 subjects were analyzed: 42 subjects in the 3-day (2% cream) group and 47 subjects in the 6-day (1% cream) therapy group Study Results There were no notable differences between the treatment groups regarding age, weight, height, concurrent diabetes, and recurrent infection. There were 11 (26%) recurrent infections in the 3-day 2% cream group and 13 (28%) recurrent infections in the 6-day 1% cream group. A distinct difference between the groups was determined for the diagnosis of vulvitis. In the 3-day cream 2% group, 13 subjects (31%) suffered additionally from vulvitis; in the 6-day cream 1% group that number was 28 (60%). This was significant statistical difference (P 0.01). Differences existed between the groups regarding clinical findings. Itching was present prior to therapy in 25 (60%) subjects in the 3-day cream 2% group, and in 39 (83%) of those in the 6-day cream 1% group. This difference is statistically significant (P 0.02). A difference was found for the symptom of burning with 18 (43%) positive findings in the 3-day cream 2% group and 30 (43%) for the 6 day cream 1% treatment (P 0.06). There was a difference between the two groups for the symptom of change of the vaginal mucose (P 0.09). Pathology was detected in 13 (41%) subjects of the 3-day cream 2% group and in 24 (51%) of the 6-day cream 1% group. Prior to therapy, cultures were positive for all subjects. Results Summary Efficacy For evaluating results until the 1 st follow-up examination, there were 39 subjects from the 3-day group and 42 subjects from the 6-day group. For 36 subjects from each group, the culture was negative. This represented 92% for 3-day group and 86% for 6-day treatment group. For evaluating the overall result, there were 36 subjects in the 3-day group and 39 subjects in the 6-day group. Out of these, 29 subjects from each group had negative cultures both after the 1 st and 4 th weeks, ie, 81% for the 3-day group and 74% for the 6-day group. For evaluating the results obtained just 1 week after the end of therapy, there were 39 subjects from the 3-day group and 42 subjects from the 6-day group. Of these, a negative finding was obtained in 31 (79%) subjects in 3-day group and in 28 (67%) subjects in 6-day group. Results regarding clinical symptoms were as follows: 1) Fluor was still present in 7 subjects of each group at the 1 st follow-up examination; 4 weeks after the end of treatment, findings had remained unchanged in the 3-day group while 6 subjects in the 6-day group still presented leukorrhea. 2) Complaints of itching were recorded in 2 subjects in the 3-day group and in 4 subjects in the 6-day group one week after the end of therapy. After 4 weeks, 3 subjects in the 3-day group and 2 subjects in the 6-day group still complained of itching. This symptom was absent prior to the start of therapy in 2 subjects of the 6- day group. Page 3 of 4
3) In the 3-day group, the symptom of burning was still present in 1 subject at the 1 st follow-up examination, and 3 subjects complained of burning at the 2 nd follow up examination after 4 weeks. In the 6-day therapy group, no burning was present at either of the follow-up examinations. In the 3-day group, burning had disappeared in all the subjects; in the 6-day group, only one subject still had this symptom. After 4 weeks, 1 subject in 3-day group and 2 subjects in 6-day group had clinically positive results for this symptom. Results Summary Safety Clotrimazole (BAY B 5097) vaginal cream was locally tolerated. Except for 1 subject in the 6-day therapy group who claimed subjective intolerance reactions (allergy), no other signs of intolerance were reported. Results Summary Other Not applicable Conclusion In this study, no difference in the results between the two therapy groups was determined for any of the criteria evaluated. Date Created or Date Last Updated 12 Aug 2011 Page 4 of 4