Purpose: To assess and compare the safety and local tolerance of
different concentrations and regimens of unoprostone isopropyl (UI) and placebo
(PL) in healthy volunteers.
Method: Double-masked, placebo-controlled, single-centre, phase I study
in which 64 healthy volunteers were randomized in a 1:1:1 ratio to PL, UI
0.06%, UI 0.12%, or UI 0.15%, respectively. One drop of the test agent(s)was
instilled twice daily (b.i.d.) in one eye and thrice daily (t.i.d.) in the fellow eye for 14 days.
Criteria for local tolerance were
subjective global local tolerance assessed by the subject using a visual
analogue scale, and ocular signs and symnptoms. Safety was assessed by
comprehensive ophthalmic examination, vital signs, and spontaneously reported
adverse events. Corneal sensitivity and pupil diameter were also assessed.
Results: There was no significant difference in local tolerance between
b.i.d. and t.i.d. regimens. There were between-treatment differences for global
local tolerance, for one symptom (burning/stinging)and one sign (conjunctival
hyperemia). PL and UI 0.06% were slightly better tolerated than UI 0.12% and UI
0.15%. Ophthalmic examination did not reveal any significant differences
between regimens and treatment groups at any assessment time. Blood pressure,
heart rate, electrocardiogram and pulmonary function values were all within
normal range with no significant difference between treatments. Regardless of
treatment group and instillation regimen, UI did not affect corneal
sensitivity, and no clinically significant change in pupil diameter was
recorded.
Conclusions: Unoprostone isopropyl was safe and well tolerated at all
studied concentrations.