Bilastine 0.6% preservative-free eye drops, an effective once-daily treatment to reduce signs and symptoms of allergic conjunctivitis: A pooled analysis of two randomized clinical trials.

BACKGROUND AND OBJECTIVE: Allergic conjunctivitis is the most common type of ocular allergy. The objective of this study was to evaluate the efficacy of a new once-daily, preservative-free, bilastine 0.6% eye drop formulation for the treatment of allergic conjunctivitis. METHODS: Two double-masked, vehicle controlled, clinical studies (a Phase 2 Dose Ranging Study and a Phase 3 Efficacy Study) were conducted to assess the efficacy of bilastine ophthalmic solution for the treatment of signs and symptoms of allergic conjunctivitis. Both studies used the Ora-CAC® Conjunctival Allergen Challenge (CAC) Model to allow observations of allergic responses under controlled conditions. Each study was analyzed separately and then combined to create an integrated dataset. RESULTS: Efficacy was achieved for the primary efficacy endpoint of ocular itching for three bilastine concentrations (0.2%, 0.4%, and 0.6%) at 15 minutes and 8 hours post-instillation and bilastine 0.6% ophthalmic solution was also efficacious at 16 hours post-instillation. Bilastine 0.6% ophthalmic solution demonstrated non-inferiority to ketotifen 0.025% at the onset of action. From the integrated data set, differences between vehicle and bilastine 0.6% were significant at all time points both at onset (15 minutes) and at a prolonged duration (16 hours) after instillation. CONCLUSION: This multi-trial assessment suggests that bilastine 0.6% ophthalmic solution is efficacious for the treatment of the signs and symptoms of allergic conjunctivitis, with a rapid and prolonged duration of action, and has a favorable safety profile. The added convenience of a once-a-day dosing regimen may contribute to patient adherence and improve their quality of life.

Bilastine 0.6% preservative-free eye drops, a once-daily treatment for allergic conjunctivitis.

BACKGROUND: Bilastine is a second-generation antihistamine approved for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. This trial evaluated the efficacy and safety of a new bilastine 0.6% preservative-free eye-drops formulation for the symptomatic treatment of allergic conjunctivitis. METHODS: This phase 3, multicenter, double-masked, randomized study evaluated the efficacy, safety and tolerability of bilastine 0.6% ophthalmic solution compared to ketotifen 0.025% and vehicle. The primary efficacy endpoint was ocular itching reduction. The Ora-CAC® Allergen Challenge Model was used to assess ocular and nasal symptoms at 15 minutes (onset of action) and 16 hours post-treatment. RESULTS: Subjects (N=228) were 59.6% male, and the mean (SD) age was 44.1 (13.4) years. Bilastine demonstrated efficacy in reducing ocular itching compared to vehicle at both onset of action and 16 hours post-treatment (P <0.001). Ketotifen showed improvement compared to vehicle 15 minutes post-treatment (P <0.001). Bilastine demonstrated statistical non-inferiority to ketotifen for all 3 post-CAC timepoints at 15 minutes post-instillation, based on an inferiority margin of 0.4. Bilastine demonstrated improvement over vehicle (P <0.05) for conjunctival redness, ciliary redness, episcleral redness, chemosis, eyelid swelling, tearing, rhinorrhea, ear and palate pruritus and nasal congestion at 15 minutes post-treatment. Ophthalmic bilastine was safe and well tolerated. Mean drop comfort scores were significantly better (P <0.05) for bilastine compared with ketotifen immediately upon instillation, and similar compared with vehicle. CONCLUSIONS: Ophthalmic bilastine effectively reduced ocular itching for 16 hours post-treatment, suggesting that it could be used as a once-daily treatment for the signs and symptoms of allergic conjunctivitis. ClinicalTrials.gov identifier: NCT03479307.

Efficacy of Once-Daily Ophthalmic Bilastine for the Treatment of Allergic Conjunctivitis: A Dose-Finding Study.

BACKGROUND AND OBJECTIVE: Bilastine is a nonsedating second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Our study aimed to evaluate the optimal dose, efficacy, and safety of a newly developed once-daily preservative-free ophthalmic formulation of bilastine for allergic conjunctivitis. METHODS: Our phase 2, single-center, double-masked, randomized trial compared the efficacy of 3 doses of a bilastine ophthalmic formulation (0.2%, 0.4%, and 0.6%) with that of vehicle for the treatment of allergic conjunctivitis. The primary efficacy endpoint was the reduction in ocular itching. The Ora-CAC Conjunctival Allergen Challenge model was used to assess ocular and nasal symptoms at the onset of action (15 minutes) and at 8- and 16-hours after treatment. Tolerance and safety were also evaluated. RESULTS: A total of 121 adults with seasonal and/or perennial ocular allergy were randomized. Bilastine ophthalmic formulations 0.2%, 0.4%, and 0.6% were significantly superior (P>.001) to vehicle for the treatment of ocular itching at 3, 5, and 7 minutes after challenge at onset of action (15 minutes) and at 8 hours after treatment. Bilastine 0.6% was also effective at 16 hours after treatment. Treatment differences for bilastine 0.6% were statistically significant (P<.001) compared to vehicle at all timepoints for tearing, eyelid swelling, and nasal symptoms. No relevant adverse events were observed. CONCLUSION: All the tested ophthalmic bilastine doses were efficacious for rapid reduction of ocular itching. The 0.6% formulation was effective up to 16 hours after treatment, making it suitable for once-daily administration. The new formulation was safe and well tolerated.

Efficacy of Once-Daily Ophthalmic Bilastine for the Treatment of Allergic Conjunctivitis: A Dose-Finding Study

Background and objectives: Bilastine is a nonsedating second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Our study aimed to evaluate the optimal dose, efficacy, and safety of a newly developed once-daily preservative-free ophthalmic formulation of bilastine for allergic conjunctivitis. Methods: Our phase 2, single-center, double-masked, randomized trial compared the efficacy of 3 doses of a bilastine ophthalmic formulation (0.2%, 0.4%, and 0.6%) with that of vehicle for the treatment of allergic conjunctivitis. The primary efficacy endpoint was the reduction in ocular itching. The Ora-CAC Conjunctival Allergen Challenge model was used to assess ocular and nasal symptoms at the onset of action (15 minutes) and at 8- and 16-hours after treatment. Tolerance and safety were also evaluated. Results: A total of 121 adults with seasonal and/or perennial ocular allergy were randomized. Bilastine ophthalmic formulations 0.2%, 0.4%, and 0.6% were significantly superior (P>.001) to vehicle for the treatment of ocular itching at 3, 5, and 7 minutes after challenge at onset of action (15 minutes) and at 8 hours after treatment. Bilastine 0.6% was also effective at 16 hours after treatment. Treatment differences for bilastine 0.6% were statistically significant (P<.001) compared to vehicle at all timepoints for tearing, eyelid swelling, and nasal symptoms. No relevant adverse events were observed. Conclusions: All the tested ophthalmic bilastine doses were efficacious for rapid reduction of ocular itching. The 0.6% formulation was effective up to 16 hours after treatment, making it suitable for once-daily administration. The new formulation was safe and well tolerated (AU)

Energy Thresholds of DNA Damage Induced by UV Radiation: An XPS Study.

This work stresses on damage at the molecular level caused by ultraviolet radiation (UV) in the range from 3.5 to 8 eV, deoxyribonucleic acid (DNA) films observed by X-ray photoelectron spectroscopy (XPS). Detailed quantitative XPS analysis, in which all the amounts are relative to sodium-assumed not to be released from the samples, of the carbon, oxygen, and particularly, nitrogen components, reveals that irradiation leads to sugar degradation with CO-based compounds release for energies above 6.9 eV and decrease of nitrogen groups which are not involved in hydrogen bonding at energies above 4.2 eV. Also the phosphate groups are seen to decrease to energies above 4.2 eV. Analysis of XPS spectra allowed to conclude that the damage on bases peripheral nitrogen atoms are following the damage on phosphates. It suggests that very low kinetic energy photoelectrons are ejected from the DNA bases, as a result of UV light induced breaking of the phosphate ester groups which forms a transient anion with resonance formation and whereby most of the nitrogen DNA peripheral groups are removed. The degree of ionization of DNA was observed to increase with radiation energy, indicating that the ionized phosphate groups are kept unchanged. This result was interpreted by the shielding of phosphate groups caused by water molecules hydration near sodium atoms.

Determination of degree of ionization of poly(allylamine hydrochloride) (PAH) and poly[1-[4-(3-carboxy-4 hydroxyphenylazo)benzene sulfonamido]-1,2-ethanediyl, sodium salt] (PAZO) in layer-by-layer films using vacuum photoabsorption spectroscopy.

Electrostatic and hydrophobic interactions govern most of the properties of supramolecular systems, which is the reason determining the degree of ionization of macromolecules has become crucial for many applications. In this paper, we show that high-resolution ultraviolet spectroscopy (VUV) can be used to determine the degree of ionization and its effect on the electronic excitation energies of layer-by-layer (LbL) films of poly(allylamine hydrochloride) (PAH) and poly[1-[4-(3-carboxy-4 hydroxyphenylazo)benzene sulfonamido]-1,2-ethanediyl, sodium salt] (PAZO). A full assignment of the VUV peaks of these polyelectrolytes in solution and in cast or LbL films could be made, with their pH dependence allowing us to determine the pK(a) using the Henderson-Hasselbach equation. The pK(a) for PAZO increased from ca. 6 in solution to ca. 7.3 in LbL films owing to the charge transfer from PAH. Significantly, even using solutions at a fixed pH for PAH, the amount adsorbed on the LbL films still varied with the pH of the PAZO solutions due to these molecular-level interactions. Therefore, the procedure based on a comparison of VUV spectra from solutions and films obtained under distinct conditions is useful to determine the degree of dissociation of macromolecules, in addition to permitting interrogation of interface effects in multilayer films.

Is success a sin? A conversation with the reverend Peter J. Gomes. Interview by David A. Light.

The difficult task of achieving worldly success while also storing up spiritual treasure is perennially with us, in good times and in bad. Today, however, as the economy has cooled and companies have demonstrated their mortality, questions about meaning and value appear more relevant, even urgent. HBR associate editor David A. Light recently spoke with the Reverend Peter J. Gomes, one of the nation's best-known preachers and the minister at Harvard University's Memorial Church, about why and how it is both possible and necessary to reconcile a life of success with a life of faith. To do so, says Gomes, you must first "get used to it"--come to terms with the age-old tension between being rich in spirit and rich in worldly goods. Second, you should "get over it"--arrive at an understanding of the value and responsibilities associated with power and wealth. Finally, "get on with it"--figure out how you can live your life spiritually while continuing to lead in the business world. For those wondering how to get on with spiritual development, Gomes cites the growing phenomenon of senior executives gathering with peers--out of shared need, not shared accomplishment--to pray, study sacred texts, and share their religious life together. He counsels that it's never too late to get on with it: We can amend life at any time, whether we're 35, 45, or 75. Gomes concludes that business will continue to be one of the most significant forces in American culture, but it will always struggle against people's need for a perspective that is beyond this world's.

RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2.

Steroids, thyroid hormones, vitamin D3, and retinoids are lipophilic small molecules that regulate diverse biological effects such as cell differentiation, development, and homeostasis. The actions of these hormones are mediated by steroid/nuclear receptors which function as ligand-dependent transcriptional regulators. Transcriptional activation by ligand-bound receptors is a complex process requiring dissociation and recruitment of several additional cofactors. We report here the cloning and characterization of receptor-associated coactivator 3 (RAC3), a human transcriptional coactivator for steroid/nuclear receptors. RAC3 interacts with several liganded receptors through a mechanism which requires their respective ligand-dependent activation domains. RAC3 can activate transcription when tethered to a heterologous DNA-binding domain. Overexpression of RAC3 enhances the ligand-dependent transcriptional activation by the receptors in mammalian cells. Sequence analysis reveals that RAC3 is related to steroid receptor coactivator 1 (SRC-1) and transcriptional intermediate factor 2 (TIF2), two of the most potent coactivators for steroid/nuclear receptors. Thus, RAC3 is a member of a growing coactivator network that should be useful as a tool for understanding hormone action and as a target for developing new therapeutic agents that can block hormone-dependent neoplasia.

Attempted preservation of one gonad in patients with bilateral germ cell tumours.

Almost all patients with early stage testicular or ovarian germ cell tumours can now expect to be cured of their disease. The preservation of fertility and sex hormone production after treatment are of importance in these predominantly young adults, especially in the uncommon cases of bilateral tumours. We present the case reports of a woman with bilateral dysgerminoma and a man with bilateral testicular seminoma, who were managed by organ-sparing surgery of the least affected gonad followed by chemotherapy. Both patients regained fertility, but a further germ tumour has developed in the man's remaining testicle. The merits and potential pitfalls of this approach are discussed.

Local anaesthesia for fibreoptic bronchoscopy: comparison between intratracheal cocaine and lignocaine.

In a double-blind study of 60 patients undergoing fibreoptic bronchoscopy we have compared the local anaesthetic effects of intratracheal injections of cocaine (4 ml, 2.5%) and lignocaine (4 ml, 4%). The two local anaesthetics were equally effective in terms of cough suppression, requirement for extra local anaesthetic, patient discomfort and operator acceptability.