DURHAM, N.C.--(Business Wire)--
Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced today patient enrollment
is complete in three of its late-stage clinical trials.
"We are pleased to be executing on our strategic plan with the achievement of
these patient enrollment milestones in the clinical development programs for
denufosol, PROLACRIA and AZASITE®,as this places us in a position to have
top-line results from all our late-stage clinical programs within 18 months. We
would like to thank the dedicated clinical investigators, study coordinators and
patients who participated in our trials as well as the Cystic Fibrosis
Foundation and its affiliates for raising awareness of the importance of
participating in clinical trials," stated Benjamin R. Yerxa, Ph.D., Executive
Vice President and Chief, Research and Development.
A possible association between Helicobacter pylori infection and eye diseases, including Sjögren syndrome, blepharitis, central serous chorioretinopathy and uveitis, has been proposed. Glaucoma is the second leading cause of blindness in the world, after cataracts, and the leading cause of irreversible blindness, but many aspects of its pathogenesis remain unknown. H pylori infection may influence the pathophysiology of glaucoma by releasing various proinflammatory and vasoactive substances, as well as by influencing the apoptotic process, parameters that may also exert their own effects in the induction and/or progression of glaucomatous neuropathy. It is difficult to understand how H pylori infection can be linked to such varied pathologies. Systemic H pylori-induced oxidative damage may be the mechanism which links oxidative stress, H pylori infection and the damage to the trabecular meshwork and optical nerve head that results in glaucoma.
PURPOSE: To investigate the ocular distribution of 1% azithromycin ophthalmic solution and the effect of polycarbophil-based mucoadhesive formulation on ocular tissue levels of azithromycin after single and multiple topical administrations in the rabbit eye.
METHODS: Rabbits were treated with either a single administration of 1% azithromycin solution with or without polycarbophil, or with multiple administrations of 1% azithromycin solution in polycarbophil. Drug concentrations were measured using LC/MS/MS. Conjunctiva, cornea, aqueous humor, and tear samples were analyzed over a period of 144 h after a single administration of azithromycin with or without polycarbophil. Eyelid, conjunctiva, cornea, aqueous humor, and tear samples were collected over a period of 288 h during and after multiple administrations of azithromycin.
RESULTS: Azithromycin was rapidly absorbed and distributed in the ocular tissues, reaching within 5 min, concentrations of 10,539 microg/mL in tear film, 108 microg/g in conjunctiva, and 40 microg/g in the cornea. The drug demonstrated tissue-specific half-lives of 15, 63, and 67 h, respectively. Following multiple administrations, the drug gradually accumulated. The polycarbophil formulation increased the bioavailability of the drug, producing peak concentrations that were between 5- and 12-fold higher than those without polycarbophil. Azithromycin also distributed rapidly in the eyelids, reaching peak concentrations of 180 mug/g at the end of the 7-day treatment, and was eliminated with a half-life of 125 h. Six days after treatment was discontinued, eyelid levels of azithromycin were above 40 microg/g.
CONCLUSIONS: Sustained and high concentrations were encountered with 7-day approved administration of 1% azithromycin formulation (AzaSite, Inspire Pharmaceuticals, Inc., Durham, NC) within all ocular surface tissues, particularly the lids. Many ocular surface disorders involving the tear film, eyelids, and adnexal structures are associated with chronic, low-grade bacterial infection and may potentially lead to decreased vision secondary to corneal scarring. Various topical antibiotic and steroid combinations with or without oral tetracyclines are commonly used with variable clinical response and known potential side effects. The clinical relevance of this study is unknown; however, the long-lasting antibacterial and additional anti-inflammatory properties of topical azithromycin might offer an effective alternative treatment option and should be explored further in clinical studies.
OBJECTIVES: The aim of this study was to assess the efficacy of Naabak(R) eyedrops in reducing inflammation in dry eye syndrome.
PATIENTS AND METHODS: This pilot, multicenter, randomized, double-blind, parallel study was carried out in adult patients suffering from moderate dry eye syndrome. Patients were treated for three months with preservative-free NAAGA (Naabak(R)) or with sodium chloride 0.9% without preservative (Larmabak(R)). They received the treatment four to six times a day during the 1(st) month and three to four times a day during the 2(nd) and 3(rd) months. At each visit (D28 and D84), clinical tests were performed as well as a biological evaluation of HLA-DR and MUC5AC expression on conjunctival imprints using flow cytometry.
RESULTS: After three months of treatment, the ocular surface symptoms and overall discomfort were improved in patients treated with Naabak(R) and in those treated with Larmabak(R) with no significant difference between the groups. Cytological impression showed a significant decrease in the expression of inflammatory markers, notably antigen HLA-DR, in the Naabak(R) group.
CONCLUSION: This study confirms the anti-inflammatory property of preservative-free NAAGA (Naabak(R)) in the context of dry eye syndrome with a similar clinical efficacy compared to sodium chloride solution (Larmabak(R)). Naabak(R) could present an additional advantage compared to artificial tears and could be indicated in the treatment of moderate inflammatory dry eye syndrome.
Purpose: To investigate the expression of CXCL9, CXCL10, CXCL11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome.
Methods: Thirty-three patients with dry eye (16 Sjögren's syndrome and 17 non-Sjögren's syndrome patients) and 15 control subjects were recruited. The concentrations of CXCL9, CXCL10, and CXCL11 in tears were measured using enzyme-linked immunosorbent assay. The correlation between chemokine levels and tear film and ocular surface parameters was analyzed. Expression of CXCL9, CXCL10, CXCL11, and CXCR3 in the conjunctiva was evaluated using immunohistochemistry. Flow cytometry was performed to count CXCR3+ cells and CXCR3+CD4+ cells in the conjunctiva.
Results: The concentrations of CXCL9, CXCL10, and CXCL11 were 1,148+/-1,088, 24,338+/-8,706, and 853+/-334 pg/ml in dry eye patients, and 272+/-269 (P=0.01), 18,149+/-5,266 (P=0.02), and 486+/-175 (P<0.01) pg/ml in control subjects, respectively. The concentrations significantly increased in tears of Sjögren's syndrome patients compared with those of non-Sjögren's syndrome patients (P<0.05). CXCL10 levels correlated significantly with basal tear secretion, and CXCL11 levels correlated significantly with basal tear secretion, tear clearance rate, keratoepitheliopathy score, and goblet cell density (P<0.05). Staining for CXCL9, CXCL10, CXCL11 and CXCR3 increased in dry eye patients, especially in Sjögren's syndrome patients. Flow cytometry demonstrated an increased number of CXCR3+ cells and CXCR3+CD4+ cells in dry eye patients.
Conclusions: Expression of CXCL9, CXCL10, CXCL11, and CXCR3 increases in the tear film and ocular surface of patients with dry eye syndrome, especially in those with Sjögren's syndrome. CXCL11 levels correlate significantly with various tear film and ocular surface parameters.
