title: Efficacy and safety of benzalkonium chloride-free fixed-dose combination of latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension.
abstract: BACKGROUND
  Benzalkonium chloride (BAK) is a common preservative in topical ocular preparations; however, prolonged use may lead to deleterious effects on the ocular surface, affecting quality of life and reducing adherence to treatment and overall outcomes. This study compared the intraocular pressure (IOP)-lowering efficacy and safety of a novel once-daily, BAK-free, fixed-dose combination of latanoprost plus timolol with latanoprost or timolol administered as monotherapy or concomitantly.
  
  
  METHODS
  This was a 6-week, randomized, open-label, parallel-group, active-controlled study in patients aged ≥18 years with open-angle glaucoma or ocular hypertension. A total of 227 patients were randomized to either a once-daily, BAK-free, fixed-dose combination of latanoprost 0.005%/timolol 0.5% ophthalmic solution or concomitant administration of once-daily latanoprost 0.005% plus twice-daily timolol 0.5% or once-daily latanoprost 0.005% monotherapy, or twice-daily timolol 0.5% monotherapy. Efficacy end points were assessed at three time points on visits at weeks 1, 2, 4, and 6 versus baseline.
  
  
  RESULTS
  The IOP-lowering efficacy of the fixed-dose combination of latanoprost/timolol was similar to that of latanoprost plus timolol administered concomitantly at all time points (mean IOP difference and 95% confidence interval within ±1.5 mmHg; P=0.4223 to P=0.9981). The fixed-dose combination of latanoprost/timolol demonstrated significantly better IOP-lowering efficacy than timolol monotherapy at all time points (P=0.001 to P<0.0001) and significantly better IOP-lowering efficacy than latanoprost monotherapy at all time points. Responder rates on at least one time point and on at least two time points with fixed-dose combination latanoprost/timolol were similar to those with concomitant latanoprost plus timolol (85.5% versus 82.1%, P=0.6360; 78.2% versus 75%, P=0.6923), but significantly better than either latanoprost or timolol monotherapy (68.5%, P=0.0355; 55.4%, P=0.0005; 57.4%, P=0.0202; and 46.4%, P=0.0006, respectively). No significant differences in ocular and nonocular treatment-emergent adverse events were found between the treatment groups.
  
  
  CONCLUSIONS
  A BAK-free, fixed-dose combination of latanoprost 0.005%/timolol 0.5% was as effective and well tolerated as concomitant latanoprost and timolol for treatment of elevated IOP in patients with open-angle glaucoma or ocular hypertension.
authors: Glaucoma Clinic, M & J Western Regional Institute of Ophthalmology, Civil Hospital, Ahmedabad, Gujarat, India.
authors: Purvi
authors: P
authors: Bhagat
authors: Glaucoma Department, PBMA's H.V. Desai Eye Hospital, Maharashtra, India.
authors: Kalyani
authors: K
authors: Sodimalla
authors: Glaucoma Service, B B Eye Foundation, Kolkata, India.
authors: Chandrima
authors: C
authors: Paul
authors: Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors: Surinder S
authors: SS
authors: Pandav
authors: Glaucoma Clinic, Aravind Eye Hospital, Coimbatore, Tamilnadu, India.
authors: Ganesh V
authors: GV
authors: Raman
authors: Glaucoma Clinic, Aravind Eye Hospital, Tirunelveli, Tamilnadu, India.
authors: Rengappa
authors: R
authors: Ramakrishnan
authors: Clinical Research Department, Sun Pharma Advanced Research Company Ltd, Mumbai, Maharashtra, India.
authors: Abhijeet
authors: A
authors: Joshi
authors: Clinical Research Department, Sun Pharma Advanced Research Company Ltd, Mumbai, Maharashtra, India.
authors: Atul
authors: A
authors: Raut
keywords: benzalkonium chloride; latanoprost; ocular hypertension; open-angle glaucoma; pharmaceutical preservatives; timolol