Impact of age, diagnosis, and history of glaucoma surgery on outcomes in pediatric patients treated with latanoprost.

PURPOSE: To evaluate the impact of age, glaucoma-specific diagnosis, and history of prior glaucoma surgery on outcomes in pediatric patients treated with latanoprost monotherapy. PATIENTS AND METHODS: Prospective, randomized, double-masked 12-week, multicenter study included individuals 18 years or younger with glaucoma. Subjects stratified by age (0 to <3, 3 to <12, 12 to 18 y), diagnosis [primary congenital glaucoma (PCG) vs. non-PCG], and baseline intraocular pressure (IOP; 22 to <27, 27 to 31, >31 mm Hg), and randomized (1:1) to latanoprost vehicle (8 AM) and latanoprost 0.005% (8 PM) or timolol 0.5% (or 0.25% for those less than 3 y old; 8 AM/8 PM). IOP and safety assessments performed and adverse events recorded at baseline, weeks 1, 4, 12. Post hoc analyses in age-specific and diagnosis-specific groups of latanoprost-treated subjects were conducted (intent-to-treat population). RESULTS: Sixty-eight subjects were treated with latanoprost (0 to <3, n=17; 3 to <12, n=26; 12 to 18, n=25); 82%, 42%, and 24%, respectively, had a primary diagnosis of PCG. Among Non-PCG subjects, 0% (0/3), 47% (7/15), and 63% (12/19) had a primary diagnosis of juvenile open-angle glaucoma in the 0 to <3, 3 to <12, and 12 to 18 year cohorts, respectively. Mean percent IOP reductions from baseline at week 12 were 22%, 24%, and 30% in the youngest through oldest age groups, respectively (P=0.3600). At week 12, a higher responder rate (≥15% IOP reduction) was observed in the non-PCG than in the PCG group (70% vs. 45%, respectively; P=0.0361). Latanoprost was well tolerated. CONCLUSION: All age and diagnosis subgroups showed clinically relevant (>20%) mean IOP reduction at week 12 with latanoprost monotherapy.

Latanoprost systemic exposure in pediatric and adult patients with glaucoma: a phase 1, open-label study.

OBJECTIVE: To evaluate short-term safety and steady-state systemic pharmacokinetics (PK) of latanoprost acid in pediatric subjects with glaucoma or ocular hypertension who received the adult latanoprost dose. DESIGN: Phase 1, open-label, multicenter study. PARTICIPANTS: Pediatric patients of 3 age groups (<3, 3-<12, and 12-<18 years) and adults (≥18 years) receiving latanoprost ophthalmic solution 0.005% once daily in 1 or both eyes for ≥2 weeks. INTERVENTION: Latanoprost was administered in both eyes each morning post-screening. Subjects returned 3 to 28 days later for evaluation of plasma concentrations, withholding morning latanoprost. At the clinic, a single drop of latanoprost ophthalmic solution was instilled into both eyes. Plasma latanoprost acid concentrations were collected predose and 5, 15, 30, and 60 minutes after administration. MAIN OUTCOME MEASURES: Latanoprost acid plasma exposure. RESULTS: The evaluable PK analysis set included data from 39 of 47 enrolled subjects. The median peak plasma concentration value was higher in the <3-year age group (166 pg/ml) versus other groups (49, 16, and 26 pg/ml for the 3-<12-year, 12-<18-year, and ≥18-year age groups, respectively). The median area under the concentration-time curve from zero to last measurable concentration value was also higher in the <3-year age group (2716 pg/min/ml) versus other groups (588, 106, and 380 pg/min/ml for the 3-<12-year, 12-<18-year, and ≥18-year age groups, respectively). Latanoprost acid was rapidly eliminated from the blood, with plasma concentrations undetectable within 10 to 30 minutes postdose in all but the <3-year age group. There were no discontinuations or dose reductions due to adverse events or treatment-emergent adverse events. CONCLUSIONS: Latanoprost acid systemic exposure was higher in younger children versus adolescents and adults, attributed primarily to lower body weight and smaller blood volume. Latanoprost acid was eliminated rapidly in all age groups and resulted in only a brief period of systemic exposure after once-daily dosing. Higher systemic exposure was not accompanied by adverse events, and on the basis of extrapolation of safety data from adults, this pilot study suggests an adequate safety margin for systemic adverse effects with use of the adult topical dose of latanoprost in pediatric patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.

Comparison of latanoprost and timolol in pediatric glaucoma: a phase 3, 12-week, randomized, double-masked multicenter study.

OBJECTIVE: To compare the efficacy and safety of latanoprost versus timolol in pediatric patients with glaucoma. DESIGN: Prospective, randomized, double-masked, 12-week, multicenter study. PARTICIPANTS: Individuals aged ≤18 years with glaucoma. METHODS: Stratified by age, diagnosis, and intraocular pressure (IOP) level, subjects were randomized (1:1) to latanoprost vehicle at 8 am and latanoprost 0.005% at 8 pm or timolol 0.5% (0.25% for those aged <3 years) twice daily (8 am, 8 pm). At baseline and weeks 1, 4, and 12, IOP and ocular safety were assessed and adverse events were recorded. Therapy was switched to open-label latanoprost pm and timolol am and pm for uncontrolled IOP. MAIN OUTCOME MEASURES: Mean IOP reduction from baseline to week 12. Latanoprost was considered noninferior to timolol if the lower limit of the 95% confidence interval (CI) of the difference was >-3 mmHg. A proportion of responders (subjects with ≥15% IOP reduction at weeks 4 and 12) were evaluated. Analyses were performed in diagnosis subgroups: primary congenital glaucoma (PCG) and non-PCG. RESULTS: In total, 137 subjects were treated (safety population; 12-18 years, n=48; 3-<12 years, n=55; 0-<3 years, n=34). Mean age was 8.8±5.5 years, and mean baseline IOP was 27.7±6.17 mmHg; 125 subjects completed the study, and 107 subjects were in the per protocol population. Mean IOP reductions for latanoprost and timolol at week 12 were 7.2 and 5.7 mmHg, respectively, with a difference of 1.5 mmHg (95% CI, -0.8 to 3.7; P=0.21). Responder rates were 60% for latanoprost and 52% for timolol (P=0.33). Between-treatment differences in mean IOP reduction for PCG and non-PCG subgroups were 0.6 mmHg (95% CI, -2.3 to 3.4) and 2.6 mmHg (95% CI, -0.8 to 6.1), respectively. Responder rates for latanoprost versus timolol were 50% versus 46% for the PCG group and 72% versus 57% for the non-PCG group. Both therapies were well tolerated. CONCLUSIONS: Latanoprost 0.005% is not inferior (i.e., is either more or similarly effective) to timolol and produces clinically relevant IOP reductions across pediatric patients with and without PCG. Both latanoprost and timolol had favorable safety profiles over the duration of this 3-month trial. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.