ABSTRACT
INTRODUCTION: The aim of this prospective crossover study was to evaluate the non-inferiority of PRO-122 (a preservative-free fixed combination) compared with 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide fixed combination (KOF) by evaluating its efficacy, tolerability and safety in subjects with controlled primary open-angle glaucoma (POAG) previously treated with KOF for at least 2 months. METHODS: In a prospective, crossover, randomized, double-masked multicenter study, patients previously treated with KOF were randomly assigned to receive either PRO-122 or KOF for 30 days. On day 31, the A sequence changed to KOF, while the B sequence received PRO-122. All patients remained in the protocol for 30 additional days for a total of 60 days. The main efficacy endpoint was maintaining the controlled intraocular pressure (IOP). The safety and tolerability of both products were assessed by the presence of adverse events (AEs), ocular findings, a questionnaire on ocular comfort and the VF-14 index. RESULTS: A total of 51 patients participated. After application of PRO-122 twice a day, its efficacy was demonstrated through maintenance of the controlled IOP in patients previously controlled with KOF. The crossover between PRO-122 and KOF and vice versa, after 30 days of use, did not affect IOP control. PRO-122 was shown not to be inferior to KOF in maintaining IOP at control levels. The safety of both drugs is similar, as neither presented drug-related AEs or differences regarding safety issues. The tolerability of the two medications-evaluated by ocular findings, the questionnaire on ocular comfort and the VF-14 index-was also determined to be similar. CONCLUSIONS: The controlled IOP in patients with controlled POAG treated with PRO-122 was maintained both in relation to the initial controlled IOP of the study and when compared with KOF in the B sequence. Finally, the treatment with PRO-122 demonstrated similar safety and tolerability to KOF. FUNDING: Laboratorios Sophia, S.A. de C.V. (Zapopan, Jalisco, México). TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03257813 (registered retrospectively).
ABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of triple fixed-combination bimatoprost 0.01%/brimonidine 0.15%/timolol 0.5% (TFC) versus dual fixed-combination brimonidine 0.2%/timolol 0.5% (DFC) in primary open-angle glaucoma and ocular hypertension. METHODS: Patients with intraocular pressure (IOP) ≥23 and ≤34 mmHg were randomized to twice-daily TFC or DFC. The primary variable is the change in worse eye mean IOP from baseline at week 12 (modified intent-to-treat (mITT) population). Secondary endpoints are mean IOP and mean change from baseline at weeks 1, 2, 4, 8, and 12 (mITT population). TFC superiority was demonstrated if the primary variable favored TFC (p ≤ 0.05). Sensitivity analyses were conducted, and safety was assessed at all visits. RESULTS: TFC (n = 93) provided greater IOP reductions from baseline than DFC (n = 97) at week 12 (treatment difference, 0.85 mmHg; p = 0.028) and all other visits. TFC was also superior to DFC in patients with high baseline IOP (i.e., IOP ≥ 25 mmHg; p ≤ 0.011). Conjunctival hyperemia, ocular irritation, and dry eye were reported more often with TFC (p ≤ 0.016); however, discontinuations for ocular adverse events were similar between treatments. CONCLUSIONS: TFC demonstrated IOP-lowering benefits that outweigh the risk of predominantly mild ocular side effects, which may be particularly relevant in patients who require greater IOP lowering to prevent/delay disease progression. This trial is registered with ClinicalTrials.gov registry number: NCT01241240.
ABSTRACT
BACKGROUND: Fixed-combination ocular hypotensives have multiple advantages, but triple-therapy dorzolamide/brimonidine/timolol (dorz/brim/tim) is only available in Latin and South America, and information on its relative efficacy is limited. This study compares the efficacy and tolerability of fixed-combination bimatoprost/timolol (bim/tim) and dorz/brim/tim in Mexican patients with primary open-angle glaucoma or ocular hypertension. METHODS: In this investigator-masked, crossover study, patients with unmet target intraocular pressure (IOP) on once-daily bim/tim or twice-daily dorz/brim/tim received the opposite medication for 3 months before returning to their pre-baseline medication for 3 months. IOP was evaluated before and after morning instillation at months 2, 3, 5 and 6. Primary endpoints were mean IOP change and Ocular Surface Disease Index© (OSDI) score at each visit. The intent-to-treat population was the a priori analysis population, but due to the number of discontinuations, the per-protocol and intent-to-treat populations were used for the primary efficacy and sensitivity analyses, respectively. RESULTS: Seventy-eight and 56 patients were included in the intent-to-treat and per-protocol populations, respectively. At month 3, statistically significant IOP reductions from baseline were observed in the bim/tim (P < 0.01) and dorz/brim/tim (P < 0.0001) groups, regardless of assessment time. At month 6, patients returned to bim/tim exhibited no significant IOP increase (regardless of assessment time), but patients returned to dorz/brim/tim exhibited a statistically significant IOP increase (P < 0.001) when assessed before instillation of study treatment. Results were similar in both intent-to-treat and per-protocol analysis populations. In the per-protocol analysis, 70% of patients on bim/tim at month 3 had an IOP <14 mm Hg, which declined to 58% (P = 0.0061) at month 6 (ie, after 3 months of dorz/brim/tim treatment). In patients receiving dorz/brim/tim at month 3, 38% had an IOP <14 mm Hg, which remained comparable after return to bim/tim. OSDI scores and incidence of adverse events were similar in both groups. CONCLUSIONS: In this first direct comparison of the efficacy of dorz/brim/tim and bim/tim, patients switched from dorz/brim/tim to bim/tim demonstrated improved/lower IOP; when returned to dorz/brim/tim, IOP increased to levels seen at study initiation, suggesting that once-daily bim/tim may have greater IOP-lowering efficacy. Both bim/tim and dorz/brim/tim were well tolerated with minimal ocular surface damage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01737853 (registered October 9, 2012).
