title: A 6-month study comparing efficacy, safety, and tolerability of the preservative-free fixed combination of tafluprost 0.0015% and timolol 0.5% versus each of its individual preservative-free components.
abstract: BACKGROUND
  The efficacy, safety and tolerability of the preservative-free (PF) fixed combination (FC) of tafluprost 0.0015% and timolol 0.5% (once daily) were compared to those of the individual components (PF tafluprost 0.0015% once daily and PF timolol 0.5% twice daily) in patients with open-angle glaucoma or ocular hypertension inadequately controlled on prior timolol or prostaglandin monotherapy for 6 months.
  
  
  METHODS
  A stratified, double-masked, randomized, multicenter phase III study was conducted. A total of 189 prior timolol users were randomized within the timolol stratum (TS) to receive either FC (n = 95) or timolol 0.5% (TIM; n = 94). Furthermore, a total of 375 prior prostaglandin analog (PGA) users were randomized within the prostaglandin stratum (PS) to receive either FC (n = 188) or tafluprost 0.0015% (TAF; n = 187). To be eligible for participation in the study, the patients were required to have an intraocular pressure (IOP) of ≥22 mmHg when on timolol (TIM) or of ≥20 mmHg when on PGA in either treated eye at the screening and end-of-run-in visits. In addition to these, the study included visits at baseline, 2 and 6 weeks, 3 and 6 months and at a post-study visit. IOP was measured at 8 a.m., 10 a.m., 4 p.m., and 8 p.m.
  
  
  RESULTS
  In the TS, a significant reduction from baseline IOP was seen with FC and TIM throughout the study. Average diurnal IOP change from baseline at month 3 was -8.55 mmHg (32%) for FC and -7.35 mmHg (28%) for TIM. The model-based treatment difference (FC-TIM) was -0.885 mmHg [95% confidence interval (CI) -1.745 to -0.024; p = 0.044] demonstrating the superiority of FC over TIM. In the PS, a significant reduction in IOP was seen with both FC and TAF throughout the study. The average diurnal IOP change from baseline at month 3 was -8.61 mmHg (33%) for FC and -7.23 mmHg (28%) for TAF. The model-based treatment difference (FC-TAF) was -1.516 mmHg (95% CI -2.044 to -0.988; p < 0.001) demonstrating the superiority of FC over TAF. In the TS, related ocular adverse events (AEs) were more frequent for patients treated with FC compared to TIM (16.8% versus 6.4%), whereas related non-ocular AEs were more frequent with TIM compared to FC (2.1% versus 0.0%). In the PS, AEs were similarly distributed between FC and TAF. The frequency of conjunctival hyperemia of FC was low (6.4%).
  
  
  CONCLUSIONS
  The preservative-free fixed combination of tafluprost and timolol provided a substantial and significant IOP reduction in both strata. The IOP reduction was superior to both tafluprost 0.0015% and timolol 0.5% when given as monotherapies. Overall, the study treatments were safe and well tolerated.
  
  
  BACKGROUND
  Santen Oy, Tampere, Finland.
authors.affiliation: Department of Ophthalmology, Mainz University Medical Center, Langenbeckstr. 1, 55101, Mainz, Germany, norbert.pfeiffer@unimedizin-mainz.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.forename: Carlo E
authors.initials: CE
authors.lastname: Traverso
authors.forename: Katrin
authors.initials: K
authors.lastname: Lorenz
authors.forename: Ville
authors.initials: V
authors.lastname: Saarela
authors.forename: Johanna
authors.initials: J
authors.lastname: Liinamaa
authors.forename: Hannu
authors.initials: H
authors.lastname: Uusitalo
authors.forename: Yury
authors.initials: Y
authors.lastname: Astakhov
authors.forename: Ernest
authors.initials: E
authors.lastname: Boiko
authors.forename: Auli
authors.initials: A
authors.lastname: Ropo
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000175:diagnosis / Q000188:drug therapy; D011310:Preservatives, Pharmaceutical; D011460:Prostaglandins F / Q000008:administration & dosage / Q000009:adverse effects; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects; D014065:Tonometry, Ocular / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D011310:Preservatives, Pharmaceutical; D011460:Prostaglandins F; C485333:tafluprost; D013999:Timolol