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R. Ritch, M. Schiewe, R. C. Zink, M. Lemp, P. L. Kaufman, R. Haque, R. K. Brazzell, J. L. Vittitow; Latrunculin B (ins115644) Reduces Intraocular Pressure (iop) in Ocular Hypertension (oht) and Primary Open Angle Glaucoma (poag). Invest. Ophthalmol. Vis. Sci. 2010;51(13):6432.
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To evaluate the safety, tolerability, and iOP-lowering effect of Latrunculin-B, a marine macrolide that sequesters actin monomers, preventing actin polymerization into microfilaments and never previously tested in humans, in patients with OHT or early POAG. ClinTrials.org Identifier NCT00443924
Subjects (n=56) with bilateral OHT or early POAG (>22mmHg) in this 4-week, Phase I, multi-center, double-masked, random ized, placebo-controlled, ascending dose study received one of four concentrations of INS115644 (0.005%, 0.01%, 0.02% or 0.05%) in one eye over 3-days (5 single dose instillations, separated by 12 hours). One eye was randomly assigned to active drug, the other to placebo (n=10 subjects per dose cohort). IOP was measured prior to initiation of treatment (Day 0) and on Days 1 and 3 at approximately 8:00 a.m. (predose days 1 and 3), 10:00 a.m., and 12:00, 4:00 and 8:00 p.m.
Following the first instillation, 0.02% INS115644 reduced IOP (mean±SD) by 3.8±2.25 mmHg (p=0.002) and 0.05% by 3.9±3.1 mmHg (p=0.004) from baseline (22.9±2.4 mmHg and 23.5+3.1 mmHg respectively) at 4 hours post-instillation. After the fifth instillation (Day 3) IOP decreased from baseline by 5.4±2.4 mmHg (p=0.004) and 2.8±2.7 mmHg (p=0.02) in the 0.02% and 0.05% cohorts respectively. Adjusting for diurnal baseline and IOP in the contralateral, placebo-treated eye, there was a maximal 12 hour hypotensive effect of 4.0±0.5 mmHg (adj mean±SE) following the fifth instillation of 0.02% on Day 3. Adverse events were few and consisted mainly of mild redness and irritation. A transient, clinically insignificant increase in central corneal thickness of ≤2.5% was noted.
In patients with OHT or POAG, twice daily INS115644 (latrunculin B) significantly lowered IOP compared to contralateral, placebo-treated eye, with few and mild ocular adverse events.
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