Evaluation of the efficacy and safety of latanoprost 0.005% without benzalkonium chloride and its noninferiority to latanoprost 0.005% with benzalkonium chloride in patients with open-angle glaucoma and ocular hypertension

Abstract

Purpose : A new formulation of latanoprost 0.005% without benzalkonium chloride (BAK) is approved for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT).
This phase 3 study evaluated if latanoprost BAK-free 0.005% ophthalmic emulsion was noninferior to latanoprost 0.005% ophthalmic solution containing BAK (reference).

Methods : In this phase 3, randomized, parallel-group noninferiority study, patients were randomized 1:1 to latanoprost BAK-free or reference, 1 drop nightly for 12 weeks into affected eye(s). The primary efficacy endpoint was IOP, measured at 8 am, 10 am, and 4 pm at baseline, and on days 7, 28, 56, and 84. To establish noninferiority, the following 3 criteria had to be met simultaneously for treatment differences in IOP: 95% confidence interval (CI) on the mean difference between treatments includes 0 mmHg for all time points (N1), the upper limit of the 95% CI <1.5 mmHg at all time points (N2), and <1 mmHg for ≥7 of 12 time points (N3). Noninferiority analyses did not use last observation carried forward. Safety assessments included adverse event (AE) reporting.

Results : Of the 578 patients randomized, all were analyzed (289 per arm). At baseline at 8 am, the least squares (LS) mean ± standard error IOP (mmHg) was 25.9 ± 0.2 for both treatment arms, with similar values at 10 am and 4 pm. On days 7, 28, 56, and 84, the LS mean reduction from baseline in IOP (mmHg) at 8 am was 6.6, 6.6, 7.1, and 6.9 vs 6.9, 7.4, 7.4, and 7.4 for BAK-free vs reference; with similar results for 10 am and 4 pm. Noninferiority criteria N1, N2, and N3 were met for 7, 12, and 4 of the 12 assessment time points, respectively.
Overall, 82.4% vs 79.9% reported ≥1 ocular AE in the BAK-free vs reference groups. The most common ocular AEs were eye pain (64.0% vs 47.1%) and ocular hyperemia (46.7% vs 49.5%). At least 1 systemic AE was reported in 18.3% vs 15.9% of patients, respectively.

Conclusions : Latanoprost BAK-free met 1 of 3 predefined noninferiority criteria (N2), significantly reduced IOP from baseline at all time points and was similarly tolerable to reference. These results are consistent with other marketed prostaglandin analogs approved for the reduction of elevated IOP in patients with OAG or OHT.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.