Efficacy and safety of bimatoprost 0.01% formulated in tight junction modulation technology compared to marketed benzalkonium chloride preserved bimatoprost 0.01% ophthalmic solution in healthy beagle dogs

摘要

Background: This study was undertaken to compare the efficacy and safety of the new technology tight junction modulation (TJM) bimatoprost 0.01% (TJM-bimatoprost), containing polyhexamethylene biguanide hydrochloride as a preservative, and marketed bimatoprost 0.01% (BKC-bimatoprost) in healthy beagle dogs.Methods: This was a cross-over study and all animals in the study were assigned to one of two treatment arms to receive either TJM-bimatoprost (n=6) or BKC-bimatoprost (n=6) ophthalmic solution. Dosing for period 1 was started on day 3 (8 am everyday) and it continued till day 12. Assessments were carried out every day at 8 am, 9 am, 2 pm and 8 pm throughout the study period till day 17.Results: For the pooled analysis (n=12 in each group) of period 1 and 2, there was a significant decrease (p0.001) in mean intra-ocular (IOP) 1 hour post administration as compared to the baseline and this trend continued all throughout the study in both treatment arms. Twenty fours after last dose, on day 12, IOP measurements were 14.20±1.59 mmHg and 13.89±1.5 mmHg in the TJM-bimatoprost and the BKC-bimatoprost group respectively. The analysis of the primary end point revealed that 95% confidence interval for the between group differences in mean IOP values were well within the pre-defined equivalence margin of ±1.5 mmHg. In terms of safety, there was no difference in mean pupillary diameter in the TJM-bimatoprost and BKC-bimatoprost group.Conclusions: The results of this study enhance our understanding of the proprietary TJM technology by establishing efficacy and safety of TJM-bimatoprost in animal models.