A randomised, double-masked comparison study of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients

Etsuko Takamura, Kazuo Tsubota, Hitoshi Watanabe, Yuichi Ohashi, Diquafosol Ophthalmic Solution Phase 3 Study Group, Akihito Kuroda, Fukuichi Oura, Hidehito Kawabata, Hidenao Ideta, Hidetoshi Yamashita, Hiroki Shiroma, Hiroko Shimizu, Hironori Aoki, Hiroshi Mishima, Hiroshi Takahashi, Hitoshi Watanabe, Ikue Takagi, Jun Kozaki, Jun Shimazaki, Katsura Kimura, Kazunori Miyata, Kazuo Ichikawa, Kazuo Tsubota, Kazutaka Kamiya, Ken Hayashi, Kenji Inoue, Kenji Sakagami, Koji Hirano, Makoto Omura, Masahiko Yamaguchi, Masakazu Yamada, Miho Enoki, Miki Sakata, Miki Uchino, Misaki Ishioka, Naoki Hamada, Naoko Kato, Naoyuki Maeda, Norihiko Yokoi, Sadao Hori, Shigeki Okamoto, Shiro Amano, Tairo Kimura, Teruo Nishida, Tetsuro Oshika, Tomoko Goto, Torao Sugiura, Toshio Kodama, Yasuko Nakamura, Yasutaka Uchihori, Yoshikazu Shimomura, Yoshinori Takahashi, Yoshitsugu Inoue, Yoshitsugu Tagawa, Yu Monden, Sadao Komemushi, Etsuko Takamura, Kazuo Tsubota, Hitoshi Watanabe, Yuichi Ohashi, Diquafosol Ophthalmic Solution Phase 3 Study Group, Akihito Kuroda, Fukuichi Oura, Hidehito Kawabata, Hidenao Ideta, Hidetoshi Yamashita, Hiroki Shiroma, Hiroko Shimizu, Hironori Aoki, Hiroshi Mishima, Hiroshi Takahashi, Hitoshi Watanabe, Ikue Takagi, Jun Kozaki, Jun Shimazaki, Katsura Kimura, Kazunori Miyata, Kazuo Ichikawa, Kazuo Tsubota, Kazutaka Kamiya, Ken Hayashi, Kenji Inoue, Kenji Sakagami, Koji Hirano, Makoto Omura, Masahiko Yamaguchi, Masakazu Yamada, Miho Enoki, Miki Sakata, Miki Uchino, Misaki Ishioka, Naoki Hamada, Naoko Kato, Naoyuki Maeda, Norihiko Yokoi, Sadao Hori, Shigeki Okamoto, Shiro Amano, Tairo Kimura, Teruo Nishida, Tetsuro Oshika, Tomoko Goto, Torao Sugiura, Toshio Kodama, Yasuko Nakamura, Yasutaka Uchihori, Yoshikazu Shimomura, Yoshinori Takahashi, Yoshitsugu Inoue, Yoshitsugu Tagawa, Yu Monden, Sadao Komemushi

Abstract

Aims: To compare the efficacy and safety of 3% diquafosol ophthalmic solution with those of 0.1% sodium hyaluronate ophthalmic solution in dry eye patients, using mean changes in fluorescein and rose bengal staining scores as endpoints. TRIAL DESIGN AND METHODS: In this multicenter, randomised, double-masked, parallel study of 286 dry eye patients with fluorescein and rose bengal staining scores of ≥3 were randomised to the treatment groups in a 1 : 1 ratio. Efficacy and safety were evaluated after drop-wise instillation of the study drug, six times daily for 4 weeks.

Results: After 4 weeks, the intergroup difference in the mean change from baseline in fluorescein staining score was -0.03; this verified the non-inferiority of diquafosol. The mean change from baseline in rose bengal staining score was significantly lower in the diquafosol group (p=0.010), thus verifying its superiority. The incidence of adverse events was 26.4% and 18.9% in the diquafosol and sodium hyaluronate groups, respectively, with no significant difference.

Conclusions: Diquafosol (3%) and sodium hyaluronate (0.1%) exhibit similar efficacy in improving fluorescein staining scores of dry eye patients, whereas, diquafosol exhibits superior efficacy in improving rose bengal staining scores. Diquafosol has high clinical efficacy and is well tolerated with a good safety profile.

Trial registration: ClinicalTrials.gov NCT01240382.

Figures

Figure 1
Figure 1
Study design. During the run-in period, a vehicle ophthalmic solution was instilled one drop at a time, six times daily for 2 weeks. During the treatment period, after randomisation, either diquafosol or sodium hyaluronate ophthalmic solution was instilled one drop at a time, six times daily for 4 weeks under double-masked conditions.
Figure 2
Figure 2
Fluorescein and rose bengal staining scores. Each compartment was graded on a scale of 0 (without any damage), 1 (partial damage), 2 (damage in more than half the area), 3 (damage in the entire area). Fluorescein: (1) superior cornea, (2) mid-cornea, (3) inferior cornea. Rose bengal: (1) nasal bulbar conjunctiva, (2) temporal bulbar conjunctiva, (3) superior cornea, (4) mid-cornea, (5) inferior cornea.
Figure 3
Figure 3
Mean change in fluorescein staining scores. Fluorescein staining scores were evaluated every 2 weeks; at the start of the run-in period, at baseline and after 2 and 4 weeks of treatment. A significant improvement from baseline was observed in both groups at all time points, and the non-inferiority of diquafosol over sodium hyaluronate was verified at the 4-week endpoint.
Figure 4
Figure 4
Mean change in rose bengal staining score. Rose bengal staining scores were evaluated every 2 weeks; at the start of the run-in period, at baseline and after 2 and 4 weeks of treatment. At week 4 (or study discontinuation), the rose bengal staining score was significantly lower in the diquafosol group than in the sodium hyaluronate group (p=0.010).
Figure 5
Figure 5
Mean change in symptom score of heaviness. The heaviness score was significantly decreased in the diquafosol group compared with the sodium hyaluronate group at week 4.
Figure 6
Figure 6
Change of clearing rate of fluorescein and rose bengal from mid-cornea. Clearing rate of the fluorescein stain from the mid-cornea and the rose bengal stain from the mid-cornea, the diquafosol group showed significant superiority over the sodium hyaluronate group at the 4-week end point.

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