Local tolerance and activity of MK-927, a novel topical carbonic anhydrase inhibitor
E. A. Lippa, H. A. von Denffer, H. M. Hofmann and F. L. Brunner-Ferber
Clinical Research Department, Merck Sharp & Dohme Research Laboratories, West Point, Pa 19486.
A three-dose, randomized, double-masked, parallel, placebo-controlled
ocular tolerance study was undertaken in 12 healthy, normal volunteers with
the water-soluble, topical carbonic anhydrase inhibitor MK-927. To our
knowledge, this constitutes the first administration of MK-927 to humans.
Ten subjects received three drops of 2% MK-927 ophthalmic solution and two
subjects received three drops of placebo (vehicle) in one randomly selected
eye. Local tolerance of 2% MK-927 was acceptable and supports further
clinical trials in patients. Significant intraocular pressure
(IOP)-lowering activity was noted when comparing IOP four hours after first
dose with that 20 hours predose in the treated eye of subjects receiving
MK-927 (mean percent change in IOP, -29.7%; mean change in IOP, -4.6 mm Hg)
as opposed to the same comparison for the contralateral, untreated eye
(-7.2% and -1.3 mm Hg, respectively). In the two subjects treated with
placebo, IOP-lowering activity was not seen in either the placebo-treated
eye (-0.4%) or the contralateral, untreated eye (+3.1%).
