Mizoue Shiro, Nitta Koji, Shirakashi Motohiro, Nitta Akiyoshi, Yamabayashi Shigeki, Kimura Tairo, Ueda Toshihiko, Takeda Ryuji, Matsumoto Shun, Yoshikawa Keiji
Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, Japan.
Department of Ophthalmology, Fukui-ken Saiseikai Hospital, Fukui, Japan.
Adv Ther. 2017 Jun;34(6):1438-1448. doi: 10.1007/s12325-017-0552-5. Epub 2017 May 15.
This study compared the efficacy and safety of adjunctive brimonidine tartrate 0.1% ophthalmic solution (brimonidine) and timolol maleate 0.5% ophthalmic solution (timolol) in prostaglandin analogue (PGA)-treated normal-tension glaucoma (NTG), assessing the non-inferiority of brimonidine in terms of intraocular pressure (IOP) reduction.
In this multicenter, randomized, investigator-masked, parallel-group, clinical study, adjunctive brimonidine or timolol was administered twice daily for 12 weeks in eyes with NTG that had been treated with PGA for at least 90 days and required additional treatment despite an IOP of 16 mmHg or less. IOP was measured on at least three visits before add-on therapy (mean baseline IOP), and at weeks 4, 8, and 12 after adjunctive administration. Systolic/diastolic blood pressure, pulse rate, and adverse events (AEs) were recorded at each visit.
A total of 152 individuals were enrolled and 128 (84.2%) were eligible for efficacy analyses. IOP in both groups at each visit decreased significantly from baseline (P < 0.001). However, the difference in the change from baseline IOP at week 12 between the brimonidine (-1.05 ± 1.81 mmHg) and timolol (-1.41 ± 1.40 mmHg) groups was 0.36 mmHg (95% confidence interval [CI] [-0.21, 0.92]), which exceeded the value of the non-inferiority margin (0.75 mmHg). Baseline systolic/diastolic blood pressure decreased significantly in both groups at certain visits (P < 0.05), while baseline pulse rates decreased significantly in the timolol group (P < 0.001), with no significant differences in the brimonidine group. AE-related treatment discontinuation occurred in 2/71 (2.8%) and 2/75 (2.7%) patients in the brimonidine and timolol groups, respectively.
This study demonstrated an add-on effect of brimonidine to PGAs, although non-inferiority of brimonidine to timolol as adjunctive therapy in PGA-treated NTG in terms of IOP reduction was not observed. Brimonidine was associated with no adverse effects on pulse rate.
Senju Pharmaceutical Co., Ltd.
UMIN Clinical Trials Registry identifier, UMIN000014810.
本研究比较了0.1%酒石酸溴莫尼定滴眼液（溴莫尼定）与0.5%马来酸噻吗洛尔滴眼液（噻吗洛尔）作为辅助用药治疗前列腺素类似物（PGA）治疗的正常眼压性青光眼（NTG）的疗效和安全性，评估溴莫尼定在降低眼压方面的非劣效性。
在这项多中心、随机、研究者设盲、平行组临床研究中，对于已接受PGA治疗至少90天且尽管眼压在16mmHg或更低仍需要额外治疗的NTG患者，每天两次给予辅助用药溴莫尼定或噻吗洛尔，持续12周。在加用治疗前至少三次就诊时测量眼压（平均基线眼压），并在辅助用药后第4、8和12周测量眼压。每次就诊时记录收缩压/舒张压、脉搏率和不良事件（AE）。
共纳入152例个体，128例（84.2%）符合疗效分析条件。两组每次就诊时的眼压均较基线显著降低（P<0.001）。然而，溴莫尼定组（-1.05±1.81mmHg）和噻吗洛尔组（-1.41±1.40mmHg）在第12周时眼压较基线变化的差异为0.36mmHg（95%置信区间[CI][-0.21,0.92]），超过了非劣效界值（0.75mmHg）。两组在某些就诊时基线收缩压/舒张压均显著降低（P<0.05），而噻吗洛尔组基线脉搏率显著降低（P<0.001），溴莫尼定组无显著差异。溴莫尼定组和噻吗洛尔组分别有2/71（2.8%）和2/75（2.7%）的患者因AE相关原因停药。
本研究证明了溴莫尼定对PGA有附加作用，尽管未观察到溴莫尼定作为辅助治疗在降低眼压方面相对于噻吗洛尔在PGA治疗的NTG中的非劣效性。溴莫尼定对脉搏率无不良影响。
参天制药株式会社
UMIN临床试验注册标识符，UMIN000014810
