title: Comparison of latanoprost and timolol in pediatric glaucoma: a phase 3, 12-week, randomized, double-masked multicenter study.
abstract: OBJECTIVE
  To compare the efficacy and safety of latanoprost versus timolol in pediatric patients with glaucoma.
  
  
  METHODS
  Prospective, randomized, double-masked, 12-week, multicenter study.
  
  
  METHODS
  Individuals aged ≤18 years with glaucoma.
  
  
  METHODS
  Stratified by age, diagnosis, and intraocular pressure (IOP) level, subjects were randomized (1:1) to latanoprost vehicle at 8 am and latanoprost 0.005% at 8 pm or timolol 0.5% (0.25% for those aged <3 years) twice daily (8 am, 8 pm). At baseline and weeks 1, 4, and 12, IOP and ocular safety were assessed and adverse events were recorded. Therapy was switched to open-label latanoprost pm and timolol am and pm for uncontrolled IOP.
  
  
  METHODS
  Mean IOP reduction from baseline to week 12. Latanoprost was considered noninferior to timolol if the lower limit of the 95% confidence interval (CI) of the difference was >-3 mmHg. A proportion of responders (subjects with ≥15% IOP reduction at weeks 4 and 12) were evaluated. Analyses were performed in diagnosis subgroups: primary congenital glaucoma (PCG) and non-PCG.
  
  
  RESULTS
  In total, 137 subjects were treated (safety population; 12-18 years, n=48; 3-<12 years, n=55; 0-<3 years, n=34). Mean age was 8.8±5.5 years, and mean baseline IOP was 27.7±6.17 mmHg; 125 subjects completed the study, and 107 subjects were in the per protocol population. Mean IOP reductions for latanoprost and timolol at week 12 were 7.2 and 5.7 mmHg, respectively, with a difference of 1.5 mmHg (95% CI, -0.8 to 3.7; P=0.21). Responder rates were 60% for latanoprost and 52% for timolol (P=0.33). Between-treatment differences in mean IOP reduction for PCG and non-PCG subgroups were 0.6 mmHg (95% CI, -2.3 to 3.4) and 2.6 mmHg (95% CI, -0.8 to 6.1), respectively. Responder rates for latanoprost versus timolol were 50% versus 46% for the PCG group and 72% versus 57% for the non-PCG group. Both therapies were well tolerated.
  
  
  CONCLUSIONS
  Latanoprost 0.005% is not inferior (i.e., is either more or similarly effective) to timolol and produces clinically relevant IOP reductions across pediatric patients with and without PCG. Both latanoprost and timolol had favorable safety profiles over the duration of this 3-month trial.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Pfizer Inc, New London, Connecticut, USA.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Maeda-Chubachi
authors.forename: Katherine
authors.initials: K
authors.lastname: Chi-Burris
authors.forename: Brad D
authors.initials: BD
authors.lastname: Simons
authors.forename: Sharon F
authors.initials: SF
authors.lastname: Freedman
authors.forename: Peng T
authors.initials: PT
authors.lastname: Khaw
authors.forename: Barbara
authors.initials: B
authors.lastname: Wirostko
authors.forename: Eric
authors.initials: E
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006871:Hydrophthalmos / Q000188:drug therapy* / Q000503:physiopathology; D007223:Infant; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D013999:Timolol / Q000008:administration & dosage* / Q000009:adverse effects; D014065:Tonometry, Ocular; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D013999:Timolol