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George Ousler, Karen Meerovitch; High CAE Responders Show Greater Improvement in Signs and Symptoms of Dry Eye after Treatment with MIM-D3. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4343.
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This post-hoc subset analysis was performed on data from a completed clinical trial of MIM-D3 Ophthalmic Solution in dry eye (Invest Ophthalmol Vis Sc 2012 53:E-Abstract) to explore differences in treatment effect when patients were stratified by baseline severity of response to a Controlled Adverse Environment (CAE). It was hypothesized that patients with greater staining or more rapid symptomatic responses to the CAE at baseline would predict which patients would react more favorably and with greater magnitudes of change to treatment with MIM-D3.
A 2-center, randomized, double-masked, placebo-controlled Phase 2 study was conducted in 150 dry eye patients. Key eligibility criteria included scores of ≥ 4, ≥ 2 and ≥ 2 for fluorescein corneal staining (FCS), lissamine green staining, and one symptom from the 4-Symptom Questionnaire. Patients also had to positively respond to CAE exposure on 2 visits with exacerbation of FCS and ocular discomfort. Eligible patients dosed BID with 1% MIM-D3, 5% MIM-D3 or placebo for 28 days and recorded symptoms in diaries. Efficacy measures were FCS post-CAE at Day 28 and diary data for the 28-day period. A post-hoc analysis separated patients by mild, moderate or severe FSC after a baseline pre to post CAE assessment. A second stratification was for time: less than or greater than 20 minutes in the CAE to reach maximal ocular discomfort. The outcome of interest was mean change in FSC from pre- to post-CAE at day 28.
A dramatic difference in treatment effect was observed when patient’s baseline CAE responses were stratified by mild, moderate and severe. Mean change from baseline FCS scores in the 1% MIM-D3 dosed group went from a -1.08 unit treatment difference to placebo (P <0.05) in the severe responders to only a -0.06 unit change in the mild responders. Similarly, patients who were hyper responsive to the CAE in symptomatology showed a greater improvement in FCS than slow responders, driving the observed ITT effect.
These post-hoc data support the hypothesis that patients with a greater or more rapid exacerbation of signs and symptoms from environmental challenges such as the CAE, are more responsive to a drug like MIM-D3, which targets mucin-protective compensatory mechanisms that turn on during an adverse challenge.
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