Dry eye disease (DED) is a keratoconjunctive disorder that "is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. The goal of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of multiple ascending doses of palovarotene ophthalmic solution in healthy adult subjects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
48
ophthalmic solution in different concentrations: Dose 1, Dose 2 and Dose 3
Placebo-to-match palovarotene ophthalmic solution vials
Algorithme Pharma facility
Québec, Canada
Number and severity of treatment-emergent ocular adverse events (TEAEs)
Time frame: from baseline until the end of study (up to 25 days)
Change in ocular safety measurements as determined by Best-Corrected Visual Acuity (BCVA)
Time frame: from baseline until the end of study (up to 25 days)
Change in Corneal Fluorescein Staining
Time frame: from baseline until the end of study (up to 25 days)
Change in intraocular pressure
Time frame: from baseline until the end of study (up to 25 days)
Plasma concentration (predose) observed at the end of a dosing interval (Ctrough)
Time frame: Day 5 and Day 6 (prior to the morning), Day 7 ((prior to the morning), Day 8, Day 9, Day 10
Area under the concentration-time curve during a dosing interval (AUCtau)
Time frame: Day 7 and Day 10
Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t)
Time frame: Day 10
Maximum observed concentration at steady state (Cmax,ss)
Time frame: Day 7 and Day 10
Average concentration at steady state (Cavg)
Time frame: Day 7 and Day 10
Apparent total plasma clearance after topical administration (CL/F)
Time frame: Day 7 and Day 10
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Time to reach Cmax at steady state (Tmax)
Time frame: Day 7 and Day 10
Apparent first-order terminal elimination half-life (t½)
Time frame: Day 7 and Day 10
Apparent first-order terminal elimination rate (k el)
Time frame: Day 7 and Day 10
Apparent volume of distribution (Vss/F)
Time frame: Day 7 and Day 10