Efficacy and safety of two new formulations of artificial tears in subjects with dry eye disease: a 3-month, multicenter, active-controlled, randomized trial

Peter A Simmons, Haixia Liu, Cindy Carlisle-Wilcox, Joseph G Vehige, Peter A Simmons, Haixia Liu, Cindy Carlisle-Wilcox, Joseph G Vehige

Abstract

Purpose: To evaluate and compare the efficacy and safety of two investigational artificial tear formulations (CHO-1 and CHO-2) containing carmellose sodium, hyaluronic acid at different concentrations, and osmoprotectants, with a standard carmellose sodium-containing formulation (Refresh Tears [RT]) in the treatment of dry eye disease.

Subjects and methods: In this 3-month, double-masked, multicenter study, subjects (n=305) were randomized 1:1:1 to receive CHO-1, CHO-2, or RT, used as needed but at least twice daily. The primary endpoint was change in ocular surface disease index (OSDI) score from baseline to day 90. Other key outcomes included symptoms evaluated on a visual analog scale, corneal and conjunctival staining, and adverse events.

Results: OSDI scores and dry eye symptoms showed a rapid and sustained reduction from baseline in each group. Both CHO-1 and CHO-2 met the primary efficacy endpoint of noninferiority to RT in day 90 OSDI score change from baseline. OSDI ocular symptoms subscale improved more with CHO-1 than CHO-2 (P=0.048). In subjects with clinically relevant baseline ocular surface staining (>14 total score of a maximum of 55), day 90 improvements were greater with CHO-1 and CHO-2 than RT (P≤0.044). Day 90 improvements in OSDI ocular symptoms subscale scores were also greater with CHO-1 than RT (P<0.007) in subjects with clinically relevant ocular staining. All treatments were well tolerated.

Conclusion: Both combination artificial tear formulations were efficacious and well tolerated in subjects with dry eye. CHO-1 demonstrated the best performance in improving ocular symptoms and reducing ocular staining in this heterogeneous study population.

Keywords: carmellose; dry eye syndromes; hyaluronic acid; ophthalmic solutions.

Figures

Figure 1
Figure 1
Subject flow through the study. Notes: “Other” reasons for discontinuation included: CHO-1, failed screening and randomized in error but not treated; patient withdrawal (n=2); CHO-2, patient withdrawal; and RT, patient withdrawal (n=2). Abbreviations: ITT, intent-to-treat; PP, per-protocol; RT, Refresh Tears.
Figure 2
Figure 2
Mean change in Ocular Surface Disease Index (OSDI) score from baseline (intent-to-treat population). Abbreviation: RT, Refresh Tears.
Figure 3
Figure 3
Median change in score from baseline at day 90 for (A) ocular symptoms, (B) vision-related functions, and (C) environmental triggers subscales of the Ocular Surface Disease Index (intent-to-treat population). Note: *P=0.048 for CHO-1 versus CHO-2 and P=0.057 for CHO-1 versus Refresh Tears (RT).
Figure 4
Figure 4
Mean symptom scores on visual analog scales for (A) burning/stinging, (B) grittiness/foreign body sensation, (C) dryness, and (D) eye ache/pain. Notes: Error bars indicate standard error of the mean (intent-to-treat population). *P=0.044 for CHO-1 versus CHO-2. Abbreviations: FBS, foreign body sensation; RT, Refresh Tears.
Figure 5
Figure 5
Mean changes in (A) corneal, (B) conjunctival, and (C) combined corneal/conjunctival staining scores from baseline (intent-to-treat population). Notes: *P≤0.036 for CHO-1 versus Refresh Tears (RT).
Figure 6
Figure 6
Mean changes in combined corneal/conjunctival staining scores from baseline in subjects stratified by the severity of baseline staining (per-protocol population). (A) Subjects with combined corneal/conjunctival staining score of ≤14 at baseline. Baseline mean scores were CHO-1, 7.7; CHO-2, 7.7; and RT, 7.8. (B) Subjects with combined corneal/conjunctival staining score of >14 at baseline. Baseline mean scores were CHO-1, 23.4; CHO-2, 21.3; and RT, 22.1. Notes: There were no significant differences between study arms in baseline mean staining scores. *P≤0.038 for CHO-1 or CHO-2 versus Refresh Tears (RT).
Figure 7
Figure 7
Mean changes in (A) corneal staining scores and (B) ocular symptoms subscale scores of the Ocular Surface Disease Index in subjects with clinically relevant staining at baseline. Notes: Error bars indicate standard error of the mean (intent-to-treat population). *P=0.009 and **P<0.007 for CHO-1 versus Refresh Tears (RT).

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Source: PubMed

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