TABLE 6.
A summary of clinical trials comparing different fixed combination and non-fixed combination agents.
| First author/Year/References | Study design | Evaluation period | Diagnosis | Glaucoma medications | Mean baseline IOP (mmHg) | Post treatment IOP (mmHg) | Adverse effects | Comments |
|---|---|---|---|---|---|---|---|---|
| Suzuki et al. (2018) | prospective, observer-masked, randomized study | 28 days | POAG | BiT-FC (18); LT-FC (14); TrT-FC (18) | 13.5 ± 4.2 mmHg | Mean 24-h IOP | — | All three fixed combinations effectively controlled IOP for 24-h and had a similar effect on diurnal and nocturnal IOP variations |
| BiT-FC: 14.6 ± 2.9 mmHg | ||||||||
| LT-FC: 14.1 ± 3.7 mmHg | ||||||||
| TrT-FC:15.8 ± 2.0 mmHg | ||||||||
| Mean diurnal IOP variation | ||||||||
| BiT-FC: 4.6 ± 2.3 mmHg | ||||||||
| LT-FC: 5.8 ± 2.4 mmHg | ||||||||
| TrT-FC: 4.3 ± 1.7 mmHg | ||||||||
| Mean nocturnal IOP variation | ||||||||
| BiT-FC: 3.2 ± 2.8 mmHg | ||||||||
| LT-FC: 2.9 ± 1.9 mmHg | ||||||||
| TrT-FC: 3.0 ± 1.6 mmHg | ||||||||
| Shoji et al. (2013) | multicenter, prospective, randomized, single-blinded, crossover clinical trial | 24 weeks with cross over at 12 weeks | NTG | LT-FC (30); TrT-FC (30) | 14.8 ± 3.3 mmHg | Mean 24-h IOP (12 weeks) | Burning eye sensation, Mild superficial punctate keratitis, Skin pigmentation: LT-FC: 5.1, 5.1, 1.7%; TrT-FC: 1.7, 1.7, 5.1% | The additional reduction in IOP was greater with TrT-FC than with LT-FC, and their tolerability profiles were similar |
| LT-FC: 13.8 ± 3.9 mmHg | ||||||||
| TrT-FC: 12.4 ± 2.90 mmHg | ||||||||
| Mean IOP change (24 weeks) | ||||||||
| LT-FC: 1.1 ± 1.3 mmHg | ||||||||
| TrT-FC: 2.4 ± 1.3 mmHg | ||||||||
| Eren et al. (2012) | randomized, double-blind, crossover study | 6 weeks | (33) OAG | LT-FC; DzT-FC | 25.09 ± 2.8 mmHg | Mean diurnal IOP | Bitter taste, Irritation and stinging, Conjunctival hyperemia, Superficial punctate keratitis (case): LT-FC: 0, 1, 2, 1; DzT-FC: 17, 7, 1, 2 | Mean diurnal IOP and peak IOP were lower with LT-FC than with DzT-FC. DzT-FC group had significant side effects of stinging and bitter taste |
| LT-FC:16.3 mmHg | ||||||||
| DzT-FC: 17.3 mmHg | ||||||||
| The peak IOP | ||||||||
| LT-FC: 18.5 mmHg | ||||||||
| DzT-FC: 19.9 mmHg | ||||||||
| Mean diurnal range | ||||||||
| LT-FC: 4.4 ± 2.2 mmHg | ||||||||
| DzT-FC: 4.6 ± 2.2 mmHg | ||||||||
| Hommer et al. (2012) | randomized, double-masked, 2-way crossover design | 6 weeks | (18) OAG | LT-FC | 25.3 ± 2.8 mmHg | The percent of IOP reduction | — | LT-FC and BrT-FC had equally effective in reducing IOP. |
| OHT | BrT-FC | LT-FC: 35.0–10.0% | ||||||
| BrT-FC: 33.6–8.8% | ||||||||
| Shim et al. (2014) | prospective, clinical study | 24 h | healthy subjects | LT-FC (30); BiT-FC (28) | LT-FC: 11.18 ± 3.27 mmHg (treated eye), 11.36 ± 3.07 mmHg (untreated eye); BiT-FC: 13.00 ± 2.12 mmHg (treated eye), 12.60 ± 2.09 mmHg (untreated eye) | The largest difference in IOP (between treated and untreated eyes) | Cojunctival hyperemia, Foreign-body sensation, Superficial punctate epitheliopathy | LT-FC and BiT-FC provided a significant reduction in IOP from baseline with no significantly difference in side effects |
| LT-FC: 1.93 mmHg (10 h after instillation) | LT-FC: 25, 17.9, 10.7% | |||||||
| BiT-FC: 1.67 mmHg (8 h after instillation) | BiT-FC: 10, 20, 13.3% | |||||||
| Konstas et al. (2014) | prospective, observer-masked, active controlled, cross-over, comparison study | 3 months | OAG | LT-FC (20); PF-TrT-FC (22) | 21.5 ± 1.6 mmHg | Mean 24-h IOP | Tear film break-up time, Corneal stain, Schirmer I test | The mean 24-h IOP lowering of TrT-FC was statistically more significant compared to LT-FC in patients |
| LT-FC: 19.3 ± 2.3 mmHg | LT-FC: 4.65 s, 1.8 s, 9.2 mm | |||||||
| PF-TrT-FC: 18.9 ± 2.2 mmHg | PF-TrT-FC: 5.15 s, 1.5 s, 9.9 mm | |||||||
| Zhao et al. (2011) | randomized, open-label, parallel-group, noninferiority study | 8 weeks | OAG, OHT | LT-FC (125); LT-nFC (125) | LT-FC: 25.8 mmHg; LT-nFC: 26.0 mmHg | Mean diurnal IOP changes | The incidence of AEs: LT-FC: 11.2%, LT-nFC: 6.5%; Conjunctival hyperemia: LT-FC: 7.2%, LT-nFC: 4.8% | The fixed-combination of latanoprost and timolol was as effective as the non-fixed combination |
| LT-FC: −8.6 mmHg | ||||||||
| LT-nFC: −8.9 mmHg | ||||||||
| Higginbotham et al. (2010) | randomized, double-masked, parallel-group study | 12 weeks | OAG, OHT | LT-FC (129); Latanoprost (134); Timolol (131) | LT-FC: 28.0 (2.2) mmHg; Latanoprost: 28.2 (2.2) mmHg; Timolol: 28.1 (2.3) mmHg | Mean diurnal IOP (6 weeks, 12 weeks) | The incidence of ocular-related AEs: LT-FC: 17.8%, Latanoprost: 23.9%, Timolol: 10.7%; Conjunctival hyperemia: LT-FC: 7.0%, Latanoprost: 10.4%, Timolol: 3.1% | LT-FC therapy is as safe and effective in lowering IOP in patients with either ocular hypertension or glaucoma as monotherapy with latanoprost or timolol |
| LT-FC: 17.9 (3.3), 17.8 (3.5) mmHg | ||||||||
| Latanoprost: 18.9 (2.9), 19.3 (3.4) mmHg | ||||||||
| Timolol: 20.9 (3.7), 20.9 (3.5) mmHg | ||||||||
| Mean diurnal IOP reductions from baseline (12 weeks) | ||||||||
| LT-FC: 73.5% | ||||||||
| Latanoprost: 57.5% | ||||||||
| Timolol: 32.8% | ||||||||
| Asrani et al. (2019) | randomized, double masked, phase 3 clinical trial | 3 months | OAG, OHT | NL-FC (238); Latanoprost (236); Netarsudil (244) | 22.4–24.8 mmHg | Mean percent of diurnal IOP changes: NL-FC: −33.7%, Latanoprost: −27.6%, Netarsudil: −22.8% | Conjunctival hyperemia | NL-FC provided clinically and statistically significantly greater IOP-lowering effect than monotherapy. The incidence rate of conjunctival hyperemia significant increases, but it is acceptable |
| NL-FC: 63.0% | ||||||||
| Latanoprost: 62.5% | ||||||||
| Netarsudil: 64.1% | ||||||||
| Conjunctival hyperemia led to treatment discontinuation | ||||||||
| NL-FC: 7.1% | ||||||||
| Latanoprost: 0% | ||||||||
| Netarsudil: 4.9% | ||||||||
| Asrani et al. (2020) | Phase 3 clinical trial | 3 months | OAG, OHT | NL-FC (483); Latanoprost (486); Netarsudil (499) | 23.6 mmHg; 23.5 mmHg; 23.6 mmHg | Mean diurnal IOP: NL-FC: 15.8 mmHg, Latanoprost: 17.3 mmHg, Netarsudil: 18.4 mmHg; The percent of IOP reduction >40%: NL-FC: 30.9%, Latanoprost: 8.5%, Netarsudil: 5.9% | Conjunctival hyperemia, Cornea verticillate, Junctival hemorrhage: NL-FC: 58.7,15.4, 10.8%; Latanoprost: 22.1, 0, 1.0%; Netarsudil: 47.0, 11.6, 14.5% | |
| Konstas et al. (2013b) | prospective, observer-masked, crossover, comparison protocol | 3 months | high-pressure exfoliation syndrome (glaucoma) | BiT-FC (21); latanoprost (20) | 31.1 mmHg | The mean 24-h IOP reduction: BiT-FC: 12.2 mmHg (39.2%), Latanoprost: 9.9 mmHg (31.9%); The mean 24-h IOP fluctuation: BiT-FC: 3.8 mmHg, Latanoprost: 4.2 mmHg | — | Comparing to latanoprost, BiT-FC had a better IOP-lowering effect. However, both medications had no difference in mean 24-h IOP fluctuation |
| Lewis et al. (2010) | identical, double-masked, parallel studies | 12 months | OHT | BiT-FC (533); Bimatoprost (n = 265); Timolol (n = 263) | 23.3–26.2 mmHg | Mean diurnal IOP reduction | The percent of treatment-related AEs | BiT-FC provided statistically significant greater reduction in IOP over the 12-months than bimatoprost and timolol monotherapies. And there is no addition AEs appeared in BiT-FC group |
| BiT-FC: 7.7 mmHg | BiT-FC: 48.0% | |||||||
| Bimatoprost: 7.6 mmHg | Bimatoprost: 60.0% | |||||||
| Timolol: 6.4 mmHg | Timolol: 31.6% | |||||||
| The percent of IOP <18 mmHg | Conjunctival hyperemia | |||||||
| BiT-FC: 23.3% | BiT-FC: 25.7% | |||||||
| Bimatoprost: 18.1% | Bimatoprost: 43.4% | |||||||
| Timolol: 8.0% | Timolol: 8.7% | |||||||
| Pfeiffer et al. (2014) | stratified, double-masked, randomized, multicenter phase III study | 3 months | OAG, OHT (prior timolol users) | PF-TfT-FC (95); Timolol (94) | — | The average diurnal IOP change: PF-TfT-FC: −8.55 mmHg (32%) | Conjunctival/ocular hyperemia: PF-TfT-FC: 9.5%, Timolol: 0% | PF-TfT-FC with a substantial and significant IOP reduction effect was superior to monotherapy. No statistically significant differences in the drop discomfort among all groups |
| Timolol: −7.35 mmHg (28%) | ||||||||
| OAG | PF-TfT-FC (188) | — | The average diurnal IOP change: PF-TfT-FC: −8.61 mmHg (33%) | Conjunctival/ocular hyperemia: PF-TfT-FC: 4.8%, Tafluprost: 3.2% | ||||
| OHT (prior prostaglandin analog users) | Tafluprost (187) | Tafluprost: 7.23 mmHg (28%) | ||||||
| Babic et al. (2013) | randomized, controlled, open-label, prospective study | 3 months | POAG, OHT | TrT-FC (30); DzT-FC (26) | 25.10 mmHg; 24.23 mmHg | Mean IOP reduction: TrT-FC: 8.96 mmHg (36.28%), DzT-FC: 8.07 mmHg (35.66%) | The most frequent ocular AEs: TrT-FC group: hyperemia (50%), blurred vision and pruritus (6.7%); DzT-FC group: dry eye sensation (30.8%), foreign body sensation (23.1%) | TrT-FC was slightly more effective than DzT-FC in reducing mean diurnal IOP. Both treatments were well tolerated and safe |
| Macky, (2014) | prospective, randomized, controlled, clinical study | 6 months | POAG | BiT-FC (40); TrT-FC (40) | 23.00 mmHg; 24.00 mmHg | Mean IOP reduction: BiT-FC: 11.17 mmHg (42.5%), TrT-FC: 7.89 mmHg (33.3%) | Ocular redness: BiT-FC: 10.0%, TrT-FC: 12.5% | BiT-FC can provide more effective IOP reduction than TrT-FC. |
| Pfeiffer and group, (2011) | double-masked | 12 weeks | OAG, OHT | TrBz-nFC (90); TrT-nFC (90) | 21.0 ± 2.2 mmHg; 21.2 ± 2.2 mmHg | Mean IOP reduction: TrBz-nFC: 3.2 ± 2.4 mmHg (14.8 ± 10.5%), TrT-nFC: 4.2 ± 2.8 mmHg (19.6 ± 12.7%) | Conjunctival hyperemia: TrBz-nFC: 8.3%, TrT-nFC: 5.4% | Timolol added to travoprost reduced IOP more effectively than brinzolamide added to travoprost |
| Yamamoto et al. (2016) | randomized, controlled, phase 3 trials | 8 weeks | POAG, OHT, NTG | LC-FC (118); Latanoprost (119) | 20.1 ± 2.2 mmHg; 20.1 ± 1.9 mmHg | Mean IOP reduction: LC-FC: 2.9 mmHg, Latanoprost: 1.6 mmHg | The incidence of drug-related AEs: LC-FC: 6.8%, Latanoprost: 4.5% | Both LC-FC and LC-nFC had comparable effects and achieved a significantly greater IOP-lowering effect than latanoprost and carteolol |
| LC-FC (78); carteolol (78); LC-nFC (37) | 19.8 ± 1.7 mmHg; 19.8 ± 2.4 mmHg; 19.7 ± 2.1 mmHg | Mean IOP reduction: LC-FC: 3.5 mmHg, carteolol: 1.6 mmHg, LC-nFC: 3.1 mmHg | The incidence of drug-related AEs: LC-FC: 19.2%, carteolol: 2.6%, LC-nFC: 16.2% | |||||
| Kim et al. (2016) | multi-institution, randomized, active-controlled, open-label, parallel-group study | 12 weeks | NTG | BrT-FC (48); Timolol (47) | 15.2 ± 3.42 mmHg; 14.58 ± 3.05 mmHg | Mean IOP: BrT-FC: 11.87 ± 2.51 mmHg, Timolol: 12.76 ± 3.14 mmHg; The ratio of IOP reduction >20%: BrT-FC: 56%, Timolol: 23.53% | The incidence of ocular AEs: BrT-FC: 18.18%, Timolol: 5.45%; The incidence of systemic AEs: BrT-FC: 1.82%, Timolol: 3.64% | BrT-FC has a superior IOP-lowering effect than timolol in NTG patients, which also has well tolerated and safe |
| Katz et al. (2012) | prospective, randomized, multicenter, investigator-masked clinical trial | 12 weeks | POAG, OHT | BrT-FC (73); Latanoprost (75) | 24.7 mmHg; 25.4 mmHg | The mean diurnal IOP: BrT-FC: 17.8 (2.9) mmHg, Latanoprost: 17.9 (3.9) mmHg; The mean change in diurnal IOP: BrT-FC: 7.0 mmHg (27.9%), Latanoprost: 7.5 mmHg (29.7%) | The incidence of AEs: BrT-FC: 21.9%, Latanoprost: 10.7%; Conjunctival hyperemia, Lid Edema: BrT-FC: 11.6%, 5.8%; Latanoprost: 16.0%, 1.3% | BrT-FC and latanoprost have similar efficacy in lowering IOP in patients with glaucoma or OHT over 12 weeks. AEs were more common in BrT-FC group, but none of the adverse events were serious |
| Gulkilik et al. (2011) | prospective study | 4 weeks | POAG | BrT-FC (42); DzT-FC (42) | 24.6 mmHg; 24.1 mmHg | The mean diurnal IOP: BrT-FC: 16.9 mmHg, DzT-FC: 17.3 mmHg | The Schirmer scores (tear function tests) (before and after): BrT-FC: 14.1 ± 2.2 and 13.2 ± 3.0 mm, DzT-FC: 13.3 ± 2.8, and 12.3 ± 3.8 mm; The tear break-up time (before and after): BrT-FC: 10.9 ± 1.9 and 9.9 ± 1.9 s, DzT-FC: 10.1 ± 1.8 and 9.1 ± 1.6 s; Burning, Foreign body sensation, Itching: BrT-FC: 19, 12, 14%; DzT-FC: 43, 28, 12% | Both BrT-FC and DzT-FC can effectively lower IOP. The side-effect profile is similar in both groups. BrT-FC reduces lesser occurrence of a burning sensation, which may improve patient compliance. Both groups significantly lower tear secretion and tear break-up time, which may lead to dry eye |
| Realini et al. (2013) | identical, phase 3, randomized, clinical trials | 3 months | OAG, OHT | BzBr-FC (424); Brinzolamide (453); Brimonidine (448) | 23.7–27.0 mmHg; 23.9–27.2 mmHg; 23.7–27.2 mmHg | The mean diurnal IOP: BzBr-FC:16.5–20.2 mmHg, Brinzolamide:19.5–21.2 mmHg, Brimonidine:18.0–22.5 mmHg | Vision blurred, Eye irritation, Ocular hyperemia, Dysgeusia, Dry mouth: BzBr-FC: 5.3, 4.1, 2.1, 3.9, 3.0%; Brinzolamide: 6.4, 1.1, 0.7, 8.3, 0.0%; Brimonidine: 0.2, 2.2, 3.3, 0.2, 2.4% | BzBr-FC had significantly superior IOP-lowering activity compared with either brinzolamide or brimonidine alone and a safety profile consistent with that of its individual components |
| Aung et al. (2014) | Phase 3, randomized, multicenter, double-masked clinical trial | 6 months | OAG | BzBr-FC (193); Brinzolamide (192); Brimonidine (175) | 25.9 ± 0.19 mmHg; 25.9 ± 0.2 mmHg; 26.0 ± 0.19 mmHg | The mean diurnal IOP reduction (weeek-2, month-3 and month-6): BzBr-FC: 7.6, 7.9, 7.8 mmHg; Brinzolamide; 6.1, 6.5, 6.7 mmHg; Brimonidine: 6.0, 6.4, 6.4 mmHg | The incidence of serious AEs: BzBr-FC: 2.6%, Brinzolamide: 1.0%, Brimonidine: 1.7%; The incidence of discontinuation: BzBr-FC: 9.3%, Brinzolamide: 0.5%, Brimonidine: 7.4%; The incidence of treatment-related AEs: BzBr-FC: 28.5%, Brinzolamide: 11.5%, Brimonidine: 22.9% | BzBr-FC had a significantly greater IOP-lowering effect than either brinzolamide or brimonidine alone and displayed a safety profile consistent with its individual components |
| Katz et al. (2013) | Phase 3, double-masked, parallel group, multicenter study | 3 months | OAG, OHT | BzBr-FC (220); Brinzolamide (220); Brimonidine (220) | 26.9–23.2 mmHg; 27.1–23.6 mmHg; 27.0–24.0 mmHg | The mean diurnal IOP reduction: BzBr-FC: 24.1–34.9%, Brinzolamide: 16.9–22.6%, Brimonidine: 14.3–25.8% | Vision blurred, Ocular hyperemia, Dry eye, Dysgeusi: BzBr-FC: 6.1, 3.3, 0.9, 3.7%, Brinzolamide: 6.2, 0.9, 0.9, 6.2%, Brimonidine: 0.5, 4.1, 2.7, 0% | BzBr-FC has significantly superior IOP-lowering activity compared with either brinzolamide alone or brimonidine alone in patients with open-angle glaucoma or ocular hypertension while providing a safety profile consistent with that of its individual components |
| Seibold et al. (2017) | prospective, multicenter, double-masked, parallel-group clinical trial | 24 h | OAG, OHT | BzBr-FC (30); Timolol (30) | The baseline 24 h IOP: 20.2 ± 0.5 mmHg, 19.8 ± 0.6 mmHg; The baseline diurnal IOP: 19.7 ± 0.5 mmHg, 19.3 ± 0.7 mmHg; The baseline nocturnal IOP: 21.8 ± 0.5 mmHg, 21.4 ± 0.6 mmHg | The mean 24 h IOP reduction: BzBr-FC: 2.0 ± 0.3 mmHg, Timolol: 1.2 ± 0.3 mmHg; The mean diurnal IOP change: BzBr-FC: 2.7 ± 0.4 mmHg, Timolol: 2.1 ± 0.43 mmHg; The mean nocturnal IOP change: BzBr-FC: 0.8 ± 0.3 mmHg, Timolol: +0.6 ± 0.2 mmHg | — | Both BzBr-FC and timolol significantly lower IOP during the diurnal period. During the nocturnal period, the effect is lessened but remains significant for BzBr-FC, while timolol fails to reduce IOP overnight |
| Nguyen et al. (2013) | Phase 3, multicenter, double-masked, parallel-group | 3 months | OAG, OHT | BzBr-FC (218); Brinzolamide (229); Brimonidine (232) | 24.1–27.2 mmHg; 27.2–24.2 mmHg; 23.7–27.3 mmHg | The mean IOP reduction: BzBr-FC: 5.4–8.4 mmHg, Brinzolamide: 4.2–5.7 mmHg, Brimonidine: 3.1–6.5 mmHg | Blurred vision, eye pruritus, dysgeusia: BzBr-FC: 4.5, 2.3, 4.1%; Brinzolamide: 6.8, 1.3, 10.3%; Brimonidine: 0, 0, 0.4%; Conjunctivitis, dry mouth, eye allergy: BzBr-FC: 1.8, 2.7, 4.5%; Brinzolamide: 0, 0, 0%; Brimonidine: 3.0, 2.1, 0.9%; The rate of discontinued participation: BzBr-FC: 11.3%, Brinzolamide: 2.1%, Brimonidine: 9.4% | BzBr-FC has significantly superior IOP-lowering activity compared with either brinzolamide or brimonidine, while providing a safety profile which is consistent with that of the individual components |
| Sezgin Akcay et al. (2013) | randomized, double-blinded, active-controlled, parallel-group trial | 3 months | OAG, OHT | BzT-FC (57); DzT-FC (57) | 24.6–29.9 mmHg | The mean IOP: BzT-FC: 16.26–18.98 mmHg, DzT-FC: 16.35–19.0 mmHg; The mean IOP reductions: BzT-FC: 6.42–9.74 mmHg (26.09–37.46%), DzT-FC: 8.16–12.41 mmHg (31.19–41.44%) | Blurred vision, Ocular irritation, Eye pain, Foreign body sensation: BzT-FC: 33.3, 7.01, 3.5, 5.2%; DzT-FC: 10.5, 33.3, 29.8, 28.07% | DzT-FC and BzT-FC provided comparable IOP-lowering effect, while greater ocular discomfort was happened in DzT-FC group. BzT-FC treatment may provide a better patient experience and improve therapeutic compliance |
| Hartleben et al. (2017) | multicenter, double-masked, randomized, phase 3 study | 12 weeks | POAG, OHT | BiBrT-FC (93); BrT-FC (97) | 24.62 ± 2.48 mmHg; 25.12 ± 2.18 mmHg | The mean IOP reductions: BiBrT-FC: 10.03 mmHg, BrT-FC: 9.18 mmHg; The proportion of IOP<13 mmHg: BiBrT-FC: 33.7%, BrT-FC: 14.8% | The incidence of treatment-related AEs: BiBrT-FC: 52.7%, BrT-FC: 27.6%; The percentage of discontinuations: BiBrT-FC: 5.4%, BrT-FC: 4.1%; Conjunctival hyperemia, Eye irritation, Dry eye, Eye pruritus, Somnolence: BiBrT-FC: 23.7, 14.0, 8.6, 6.5, 4.3%; BrT-FC: 3.1, 4.1, 1.0, 2.0, 8.2% | BiBrT-FC had superior ocular hypotensive effects (compared with BrT-FC). Although, the ocular side effects of BiBrT-FC are more serious than BrT-FC, BiBrT-FC offers IOP-lowering benefits that may outweigh the risk |
| Belfort et al. (2020) | randomized, masked, controlled, phase III study | 12 weeks | POAG, OHT | BiBrT-FC (90); BrT-FC (95) | 25.4 mmHg; 24.4 mmHg | The mean IOP: BiBrT-FC: 15.0 mmHg, BrT-FC: 16.0 mmHg; The mean IOP reductions: BiBrT-FC: 10.45 mmHg, BrT-FC: 8.28 mmHg | The incidence of treatment-related AEs: BiBrT-FC: 72.2%, BrT-FC: 53.7%; Conjunctival hyperemia, Eye pruritus: BiBrT-FC: 47.8%, 12.2%; BrT-FC: 23.2%, 4.2% | BiBrT-FC provided clinically and statistically significantly superior IOP-lowering efficacy than did DFC with no unexpected AEs or marked worsening of expected AEs arising from the combination of these 3 medications into 1 ophthalmic solution |
| Fechtner et al. (2011) | prospective, randomized, multicenter, investigator-masked, parallel-group study | 12 weeks | OAG | BrT-FC + Latanprost (102); LT-nFC (102) | 23.4–23.7 mmHg; 23.0–23.5 mmHg | The mean IOP: 15.1–17.0 mmHg; 16.9–17.7 mmHg | The incidence of treatment-related AEs: BrT-FC + Latanoprost: 9.8%, LT-nFC: 3.9%; The incidence of ocular AEs: BrT-FC + Latanoprost: 8.8%, LT-nFC: 6.9 | BrT-FC reduces IOP significantly more effectively than timolol when used as therapy adjunctive to latanoprost. Adjunctive treatment with BrT-FC was also well tolerated |
| Konstas et al. (2013a) | prospective, observer-masked, active controlled, crossover, comparison | 3 months | POAG | BzT-FC + Travoprost (23); BrT-FC + Travoprost (27) | 20.1 mmHg | The mean 24 h IOP: BzT-FC + Tr: 17.2 mmHg, BrT-FC + Tr: 18.0 mmHg; The mean 24 h IOP fluctuation: BzT-FC + Tr: 3.6 mmHg, BrT-FC + Tr: 4.3 mmHg | Hypertrichosis, Systemic hypotension, Dry eye sensation | BzT-FC + Travoprost achieves a better mean 24-h IOP control |
| Konstas et al. (2008) | prospective, observer-masked, placebo controlled, crossover, comparison | 3 months | (31) OAG | DzT-FC + Latanoprost; DzT-FC; LT-FC | 22.1 mmHg | The mean IOP reduction: DzT-FC + Latanoprost: 5.6 mmHg, DzT-FC: 2.2 mmHg, LT-FC: 2.7 mmHg; The mean 24 h IOP fluctuation: DzT-FC + Latanoprost: 3.6 mmHg, DzT-FC: 4.4 mmHg, LT-FC: 4.1 mmHg | Burning/stinging; Watering; Superficial punctate keratitis | DzT-FC + Latanoprost demonstrates the greatest pressure reduction |
| Hatanaka et al. (2010) | prospective, open-label, randomized, controlled clinical Trial | 4 weeks | OAG | DzT-FC + Latanoprost (49); Latanoprost (49) | 15.24 ± 2.84 mmHg; 15.34 ± 2.96 mmHg | The mean IOP: DzT-FC + Latanoprost: 14.44 ± 3.03 mmHg, Latanoprost: 15.60 ± 3.09 mmHg | — | DzT-FC as an adjunct to latanoprost may further enhance pressure reduction |
| Konstas et al. (2017) | prospective, observer-maske, crossover, comparison | 24 h | OAG | PF-DzT-FC + PF-Tafluprost (21); PF-Tafluprost (22) | 22.2 ± 2.9 mmHg | The mean 24 h IOP: PF-DzT-FC + PF-Tafluprost: 17.3 ± 2.7 mmHg, PF-Tafluprost: 21.9 ± 3.2 mmHg; The mean Daytime IOP: PF-DzT-FC + PF-Tafluprost: 17.0 mmHg, PF-Tafluprost: 22.3 mmHg; The mean Nighttime IOP: PF-DzT-FC + PF-Tafluprost:17.6 mmHg, PF-Tafluprost: 21.5 mmHg | Corneal stain (van Bijsterveld score), Schirmer test (mm), Break-up time (s): PF-DzT-FC + PF-Tafluprost: 1.7, 8.2, 6.1; PF-Tafluprost: 1.3, 9.1, 6.7; Stinging, Hyperemia, Blurring of vision, Itchiness: PF-DzT-FC + PF-Tafluprost: 20.9, 9.3, 4.6, 2.3%; PF-Tafluprost: 6.9, 11.6, 6.9, 6.9% | The combination of PF-DzT-FC and PF-Tafluprost provided statistically greater 24-h efficacy and improved tolerability |
| Topouzis et al. (2021) | Phase 4, randomized (1:1), double masked, parallel group trial | 6 weeks | OAG | BrBz-FC + PGA (96); PGA (92) | 28.8 mmHg; 28.9 mmHg | The mean diurnal IOP change: BrBz-FC + PGA: −5.59 mmHg, PGA: 2.15 mmHg | The incidence of ocular AEs: BrBz-FC + PGA: 21.1%, PGA: 8.7%; Ocular hyperemia, Conjunctival hyperemia, Dry mouth: BrBz-FC + PGA: 5.3, 4.2, 5.3%; PGA: 1.1, 1.1, 0% | BrBz-FC as an adjunct to PGA is a suitable treatment option for patients with open-angle glaucoma or ocular hypertension for whom PGA monotherapy provides insufficient IOP reduction. The safety profile of BrBz-FC + PGA was consistent with the known safety profiles of brinzolamide, brimonidine, and PGAs |
| Fechtner et al. (2016) | multicenter, randomize, double-masked, parallel-group trial | 6 weeks | OAG | BrBz-FC + PGA (88); PGA (94) | 22.7 ± 2.1 mmHg; 22.4 ± 2.8 mmHg | Mean diurnal IOP change: BrBz-FC + PGA: −5.7 ± 0.3 mmHg (−24.7 ± 1.3%), PGA: −1.9 ± 0.3 mmHg (−8.2 ± 1.2%) | The incidence of ocular AEs: BrBz-FC + PGA: 35.5%, PGA: 21.1%; Blurred vision: BrBz-FC + PGA: 9.7%, PGA: 6.3% | Adding BrBz-FC to PGA therapy produced a mean diurnal IOP reduction of 5.7 mmHg (25%). BrBz-FC was superior PGA monotherapy, which was well-tolerated and no safety concerns |