Safety and efficacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled Phase 2 clinical trial in patients with dry eye.

PURPOSE: To evaluate the safety and efficacy of ophthalmic MIM-D3, a tyrosine kinase TrkA receptor agonist, in patients with dry eye. DESIGN: A prospective, two-center, randomized, double-masked, placebo-controlled Phase 2 study. METHODS: A total of 150 dry eye patients were randomized 1:1:1 to study medication (1% MIM-D3, 5% MIM-D3, or placebo) and dosed twice daily (BID) for 28 days. Key eligibility criteria included exacerbation in corneal staining and ocular discomfort in the Controlled Adverse Environment (CAE(SM)) on two visits, separated by 1 week of BID dosing with artificial tears. Safety and efficacy were evaluated at baseline, throughout treatment, and for 2 weeks post-treatment. The pre-specified primary outcome measures were fluorescein corneal staining post-CAE at day 28 and diary worst symptom scores over 28 days. Secondary outcomes included the pre-, post-, and the change from pre- to post-CAE fluorescein and lissamine green staining in both corneal and conjunctival regions, as well as individual diary symptoms. RESULTS: The prespecified primary endpoints were not met. Compared with placebo, fluorescein corneal staining at day 28 was significantly improved (P < 0.05) in the 1% MIM-D3 group for the assessment of change from pre-CAE to post-CAE. In addition, following CAE exposure, patients in the 1% MIM-D3 group showed significant improvements versus placebo (P < 0.05) in inferior fluorescein and lissamine green staining after 14 and 28 days. Compared with placebo, patients in the 5% MIM-D3 group reported significantly lower daily diary scores for ocular dryness (P < 0.05). In a subgroup defined by higher symptom scores during the run-in period, significant treatment effects (P < 0.05) were observed for diary symptoms for both MIM-D3 doses. Ocular adverse events were mild and not considered to be treatment-related. CONCLUSION: Treatment with topical ophthalmic MIM-D3 demonstrated protection against the effects of a CAE challenge on dry eye signs, reduced patient-reported diary symptoms, with a favorable safety profile.

A randomized trial of the efficacy of hand disinfection for prevention of rhinovirus infection.

BACKGROUND: Hand disinfection is frequently recommended for prevention of rhinovirus (RV) infection and RV-associated common colds. The effectiveness of this intervention has not been established in a natural setting. The purpose of this study was to determine the effect of hand disinfection on RV infection and RV-associated common cold illness in a natural setting. METHODS: A controlled clinical trial was done in young adult volunteers during 9 weeks of the fall 2009 RV season. Volunteers were randomized to either an antiviral hand treatment containing 2% citric acid and 2% malic acid in 62% ethanol (n = 116) or to a no-treatment control group (n = 96). The hand treatment was applied every 3 hours while the subjects were awake. All volunteers kept a daily diary of symptoms and had a nasal lavage for polymerase chain reaction once each week and 2 additional lavages around the time of each common cold illness. The primary endpoint was the number of RV-associated illnesses. The incidence of RV infection and of common cold illnesses were evaluated as secondary endpoints. RESULTS: The hand treatment did not significantly reduce RV infection or RV-related common cold illnesses. The total number of common cold illnesses was significantly reduced in the intent-to-treat analysis, but this effect was not seen in the per protocol analysis. CONCLUSIONS: In this study, hand disinfection did not reduce RV infection or RV-related common cold illnesses. CLINICAL TRIALS REGISTRATION: NCT00993759.

Effect of varying dispenser point source density on mating disruption of Grapholita molesta (Lepidoptera: Tortricidae).

Hand-applied dispensers are successfully used in mating disruption programs, but cost of labor to apply these dispensers limits their adoption. Creating hand-applied dispensers that release larger amounts of pheromone and that can be applied at lower densities per hectare could reduce the cost of mating disruption and increase its use. The effect of reducing the number of point sources per hectare while keeping the amount of pheromone applied per hectare constant on the success of Grapholita molesta (Busck) (Lepidoptera: Tortricidae) mating disruption was investigated with Confuse-OFM, paraffin disk, and Isomate-M Rosso dispensers. For all dispensers, as point source density decreased, numbers of moths captured increased, percentage of orientation disruption to traps decreased, and variability in these measures increased. Decreasing point source density, even while keeping the amount of pheromone applied per hectare constant is not a viable option for reducing the cost of G. molesta mating disruption with hand-applied dispensers. Puffers (aerosol dispensers) are applied at 2.5-5 dispensers per ha for G. molesta control. However, hand-applied dispensers fail when clumped at such low numbers of release sites. Potential explanations for the success of Puffers and the failure of hand-applied dispensers at very low point source densities are presented. The utility of paraffin disk dispensers as experimental devices also is discussed.