A 12-month, multicenter, randomized, double-masked, parallel-group comparison of timolol-LA once daily and timolol maleate ophthalmic solution twice daily in the treatment of adults with glaucoma or ocular hypertension

BACKGROUND: Timolol maleate, a nonselective beta-adrenoceptor antagonist applied topically to the eye as a solution, is well known for its ocular hypotensive efficacy. A gellan formulation of timolol maleate is given once daily and has been shown to be as effective as timolol maleate solution, but is associated with ocular symptoms that may limit its utility. A new timolol maleate solution has been formulated that contains potassium sorbate (timolol-LA [TLA; Istalol(R)]) to enhance the ocular bioavailability of timolol instilled into the eye, as well as half the benzalkonium chloride preservative found in timolol maleate. OBJECTIVE: The objective of this trial was to assess the ocular hypotensive efficacy and safety profile of TLA 0.5% solution once daily with those of timolol maleate ophthalmic solution (TIM) 0.5% twice daily in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: This multicenter, prospective, randomized, double-masked, parallel-group clinical trial was conducted at 21 participating private practices across the United States. Patients aged > or =18 years with OAG or OHT in 1 or both eyes and an unmedicated intraocular pressure (IOP) of > or =22 mm Hg were randomized to receive either TLA once daily or TIM twice daily bilaterally for 12 months. The primary outcome measure was IOP (95% CIs) on treatment difference at each visit (ie, equivalence analysis). The safety profile was assessed based on biomicroscopic and ophthalmoscopic examination and patient symptoms. RESULTS: A total of 332 patients (203 women, 129 men; mean [SEM] age, 64.6 [11.8] years [range, 29-92 years]) entered the study. Of these, 290 patients (87.3%) completed it. At none of the visits did the 95% CIs for between-treatment comparisons exceed 1.5 mm Hg and, at most of the visits, these intervals did not exceed 1.0 mm Hg. Mean baseline IOP was approximately 25 mm Hg in both groups. IOP was reduced at all posttreatment visits to 18 to 19 mm Hg at peak and to approximately 19 to 20 mm Hg at trough drug level in both treatment groups. Mean reductions from baseline were 6 to 7 mm Hg at peak and 5 to 6 mm Hg at trough (25.5%-28.7% and 20.8%-24.7%, respectively). Seventeen patients (5.1%) withdrew due to adverse events (AEs) (10 patients [6.0%] and 7 patients [4.2%] in the TLA and TIM groups, respectively). Based on biomicroscopic and ophthalmoscopic examination and volunteered symptoms, the safety profile was similar between the 2 treatments, except for burning and stinging on instillation, with an incidence of 41.6% in the TLA group and 22.9% in the TIM group (P = 0.001). Nearly all cases of burning and stinging were mild (94.2% [65 events] with TLA and 90.0% [36 events] with TIM), and none of the patients discontinued treatment due to this AE. Conclusions: TLA solution, a nonselective beta-adrenoceptor antagonist, given once daily in the morning, was found to be statistically equivalent in ocular hypotensive efficacy (as defined a priori) compared with TIM, given twice daily, and with an acceptable safety profile in this study population of adult patients.