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  Title	A phase III study comparing preservative-free latanoprost eye drop emulsion with preserved latanoprost in open-angle glaucoma or ocular hypertension
  ID	7267455
  External ID	7579003158
  Author	Unknown
  Published Date	Feb. 25, 2025, 8:42 a.m.
  Summary	Study design A Phase III, prospective, parallel, multinational, multicentre, double-masked, randomised, active-controlled, non-inferiority study (EudraCT: 2017-004262-95) was conducted to compare eff
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  URL	https://www.nature.com/articles/s41433-025-03646-z
  Sentiment	Negative: 0.01737    Neutral: 0.93171    Positive: 0.05092
  Relevance	0.00000

• Content Details

  Content ID	4572701
  Key	ec42c223-d477-4665-a552-2505df5460e4
  Content	Study design A Phase III, prospective, parallel, multinational, multicentre, double-masked, randomised, active-controlled, non-inferiority study (EudraCT: 2017-004262-95) was conducted to compare efficacy and safety of preservative-free latanoprost eye drop emulsion (preservative-free cationic emulsion formulation of latanoprost 0.005% [Santen Oy, Catiolanze®]) with preserved latanoprost (latanoprost 0.005% eye drop solution [Pfizer, Xalatan®]) in patients with OAG or ocular hypertension (OHT) over a 12-week period (Period 1), followed by a 12-month open-label period of preservative-free latanoprost eye drop emulsion treatment. A subset of patients who attended the Week 12 visit, and agreed to participate, continued preservative-free latanoprost eye drop emulsion treatment or switched to preservative-free latanoprost eye drop emulsion. The purpose of the open-label extension was to evaluate the long-term safety, tolerance, and efficacy of preservative-free latanoprost eye drop emulsion (Supplementary Fig. 1). Here, we report results from the 12-week non-inferiority period. The study was conducted in 47 sites across Austria, Belgium, Estonia, Finland, France, Germany, Italy, Latvia, Poland, Spain, United Kingdom, Russia and South Korea. The final protocol, its amendments, Informed Consent Form, relevant supporting information and patient recruitment information were approved by an Independent Ethics Committee and/or Institutional Review Board prior to study initiation. The study was conducted in accordance with International Council for Harmonisation of Good Clinical Practice. Written informed consent was obtained from all patients. Preserved latanoprost was requested as a study reference drug by the European Medicines Agency. Patient population Male and female patients with OAG or OHT aged ≥18 years under monotherapy glaucoma treatment, with a stable visual field (6 months), and a post-washout IOP of ≥22 mmHg (≥1 eye) and ≤32 mmHg in each eye were included in the study. Key exclusion criteria included current glaucoma treatment with a fixed-dose combination or >1 therapy in either eye, or with an oral drug (within 6 months), corneal abnormalities, significant visual field loss (absolute defect in the 10° central point or mean deviation worse than −12 decibels), optic nerve abnormality (as determined by ophthalmoscopy in either eye), optic neuropathy changes (e.g., increase in cupping since the last examination or optic nerve haemorrhage in either eye), severe blepharitis and/or meibomian gland dysfunction (MGD), ocular infection or severe dry eye disease (DED) (CFS grade 4, modified Oxford Scale), current/anticipated steroid use (oral/topical/depot), intraocular surgery (within 6 months), refractive surgery (within 1 year), any history of filtering surgery, and pregnancy or breastfeeding. Treatment At the screening visit, a washout phase of ≥5 days to 4 weeks (determined by the IOP-lowering medication used) was conducted. This lasted 4 weeks for prostaglandin analogues, ≥3 to ≤4 weeks for topical beta blockers, ≥5 days to ≤4 weeks for topical carbonic anhydrase inhibitors, and ≥2 weeks to ≤4 weeks for all other IOP-lowering medication. During the washout phase, patients received brinzolamide twice daily; brinzolamide administration was stopped 5 days before randomisation. Patients were randomised 1:1 to receive either preservative-free latanoprost eye drop emulsion (preservative-free cationic emulsion formulation of latanoprost 0.005%) or preserved latanoprost (latanoprost 0.005% eye drop solution) once daily at 9:00PM. Endpoints The primary efficacy endpoint was the change from baseline in peak (9:00 A.M. ±1 h) and trough (4:00 P.M. ±1 h) IOP at Week 12. The non-inferiority margin was ≤1.5 mmHg 95% confidence interval (CI) for between-arm treatment difference. Key secondary endpoints were changed from baseline in CFS score at Week 12 in patients with baseline CFS score ≥ 1 and change from baseline in OSD symptom score (average of 3 symptoms: dry eye sensation, blurred/poor vision, and burning/stinging/itching) at Week 12 in patients with baseline average symptom score > 0. Other pre-specified secondary endpoints were change from baseline in IOP at Week 4 peak and trough, change from baseline in mean diurnal IOP (post-washout baseline IOP) at Week 12, IOP reduction of ≥20%, ≥25% and ≥30% from baseline at Week 12 peak and trough, IOP ≤ 18 mmHg at Week 12 peak and trough, Patient Global Rating of Treatment at Week 12, quality of life, tear-film breakup time (TFBUT), conjunctival hyperaemia and slit lamp examination (MGD, conjunctiva chemosis, and lid and tear film debris) at Weeks 4 and 12, and safety. Efficacy and safety assessments IOP was measured using calibrated manual Goldmann applanation tonometry. Measurement was performed by the same investigator and same recorder throughout the study. The modified Oxford scale was used to grade CFS, and measures involved examination of the eye at a slip lamp using a yellow barrier filter and cobalt blue illumination to enhance visibility of staining. OSD symptoms were graded as 0 (absent), 1 (mild), 2 (moderate), 3 (severe) or 4 (very severe). To assess Patient Global Rating of Treatment, patients were asked to select one of the following four choices: unsatisfactory, not very satisfactory, satisfactory, or very satisfactory. At each visit, TFBUT was measured twice in each eye: 2 μL of non-preserved 2% sodium fluorescein was instilled onto the bulbar conjunctiva of each eye without inducing reflex tearing by using a micro-pipette. The TFBUT value was the average of two or three measurements. Conjunctival hyperaemia was measured at Weeks 4 and 12 using a slit lamp and scored using the photographic scale derived from McMonnies scale (1–6). Safety assessment included reported adverse events (AEs) and treatment-related AEs, best-corrected distance visual acuity and slit-lamp examination of both eyes. Each AE was classified into a System Organ Classification and coded to a preferred term and a lowest level term using Medical Dictionary for Regulatory Activities Version 23.1. Statistics: randomisation and stratification The planned sample size was determined assuming a mean difference in IOP change from baseline of 0 mmHg and a common standard deviation (SD) of 4.3 mmHg in the peak or trough IOPs, respectively, for the comparison between the preservative-free latanoprost eye drop emulsion and the preserved latanoprost arms. Three hundred and eighty patients (190 per treatment arm) would provide 90% power to demonstrate non-inferiority of preservative-free latanoprost eye drop emulsion compared with preserved latanoprost (one-sided α = 0.025) for a non-inferiority margin at 95% CI for treatment difference of ≤1.5 mmHg, assuming a 10% dropout rate. The difference in change from baseline in peak and trough IOP between two treatment arms at Week 12 was compared using a mixed-effects model for repeated measures (MMRM). A separate MMRM included treatment, visit and treatment-by-visit interaction as fixed effects, and baseline IOP at peak or trough and country as covariates. Within-patient errors were modelled using an unstructured covariance matrix. To control for overall Type 1 error rate associated with the multiple comparisons on the primary and key secondary endpoints at the 0.05 level (two-sided), a hierarchical testing strategy was employed. For the primary comparison, the difference between the two treatment groups in change from baseline in both peak and trough IOP at Week 12 9 A.M. and 4 P.M. had to meet the non-inferiority criterion that the upper limit of the one-sided 97.5% CI was ≤1.5 mmHg. If this was achieved, statistical testing for the key secondary endpoints was conducted sequentially according to hierarchical fixed sequence procedure. Regarding CFS at Week 12, if the hypothesis was rejected at 0.05 significance level (two-sided), OSD measure at Week 12 was tested. In addition to overall Type 1 error control between primary and secondary endpoints, 95% CIs and nominal p-values (non-adjusted) are reported for all other statistical tests. Statistical analyses were performed using the SAS® (Statistical Analysis Software) software version 9.4. Randomisation was stratified according to the CFS score of the study eye at baseline (CFS ≤ 1 versus CFS ≥ 2, modified Oxford scale). Efficacy was assessed in the full analysis set (FAS), consisting of all randomised patients who received at least one dose of the study medication, and provided at least one post-baseline IOP measurement at peak and trough timepoints. Sensitivity analysis of the primary efficacy endpoint was performed in the per-protocol population (all patients of the FAS without any of the major protocol deviations that could affect the primary efficacy endpoint; see Supplementary Statistical Information for further details). The safety population comprised all patients who received at least one dose of the study medication.
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  Publisher Name	Nature (#2153)
  Publisher URL	https://www.nature.com/
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  Trust Flow Score	61
  Citation Flow Score	58

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  Data Source Name	Quantexa News (#5)
  Data Source Type	news
  Data Source URL	https://app.aylien.com/dashboard
  Description	Welcome to Quantexa News API — the most powerful way to aggregate, filter, and integrate global news data into your apps and models.
  Weight	10