Safety of fixed-dose loratadine/montelukast in subjects with allergic rhinitis.

The safety of loratadine (second-generation antihistamine) and montelukast (leukotriene receptor antagonist) as monotherapies is well documented. Safety of the fixed-dose, single-tablet therapy loratadine/montelukast (L/M; SCH 445761, containing loratadine [10 mg]/montelukast [10 mg]), for treatment of the symptoms of allergic rhinitis in >3800 subjects is described. Safety data from 19 randomized clinical studies in which subjects were administered L/M are presented. Adverse events (AEs) were defined as any unfavorable and unintended sign, symptom, or laboratory data, including onset of new illness and exacerbation of preexisting conditions. Only AEs with an onset during the treatment period (i.e., treatment emergent) are summarized. Safety was also assessed via clinical laboratory evaluations and monitoring of vital signs and electrocardiogram (ECG). Overall, the incidence of AEs reported with L/M in the 19 studies was low and comparable with placebo, loratadine monotherapy, and montelukast monotherapy. The most frequently reported AE across all studies was headache. Most AEs were not severe and the duration of such events was short lived. Three AEs (headache [4.5%], fatigue [1.2%], and pharyngolaryngeal pain [1.2%]), regardless of relation to treatment, were reported by >1% of subjects in the L/M treatment group of multiple-dose, placebo-controlled studies. There were no clinically significant changes in clinical laboratory analyses or in vital signs, physical findings, or ECG found to be clinically relevant. Administration of the fixed-dose, single-tablet formulation of L/M was well tolerated. In these clinical studies, the safety of L/M was comparable with placebo, loratadine, and montelukast.

Intranasal mometasone furoate alleviates the ocular symptoms associated with seasonal allergic rhinitis: results of a post hoc analysis.

BACKGROUND: Burdensome symptoms of allergic rhinitis (AR) include nasal and ocular symptoms such as itching, tearing and redness. Intranasal corticosteroids are efficacious in the treatment of nasal symptoms of AR. OBJECTIVE: It was the aim of this study to determine the efficacy of the intranasal corticosteroid mometasone furoate nasal spray (MFNS) in relieving ocular symptoms associated with seasonal AR (SAR). METHODS: Ocular symptom data were analyzed for subjects >or=12 years of age, randomized to MFNS 200 mug q.d. (n = 176) or placebo (n = 177) in a placebo-controlled, double-blind clinical trial. Post hoc efficacy analysis assessed the mean change from baseline in subject-reported total ocular symptom scores (TOSS) averaged over the treatment period. RESULTS: Mean baseline TOSS was 4.91 for the MFNS group and comparable (5.05) for the placebo group - combined average for individual symptoms such as itching, tearing and redness ranged from 0 (no symptoms) to 9 (all symptoms, severe). Mean change from baseline in TOSS averaged over days 1-15 was -1.42 for the MFNS group and -0.94 for the placebo group (p = 0.02), for an observed treatment difference of 0.49 (statistical data rounded to 2 decimal positions). Improvement in individual symptoms (eye itching, tearing and redness) contributed to this treatment effect; the greatest improvement occurred with tearing, which decreased -0.52 from the baseline score 1.59 in the MFNS group and -0.31 from 1.67 in those receiving placebo (p < 0.01), for an observed treatment difference of 0.21. Treatment with MFNS was safe and well tolerated. CONCLUSION: MFNS is effective in reducing ocular symptoms of SAR, in addition to its established efficacy in reducing nasal symptoms of SAR.

Rhinosinusitis: Developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication, "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

Rhinosinusitis: developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

Effective dose range of mometasone furoate nasal spray in the treatment of acute rhinosinusitis.

BACKGROUND: Mometasone furoate nasal spray (MFNS) 400 microg, twice daily, as adjunctive treatment with oral antibiotic significantly improved symptoms of recurrent rhinosinusitis. OBJECTIVE: To evaluate the effectiveness and safety of MFNS 200 microg, twice daily, and 400 microg, twice daily, compared with placebo as adjunctive treatment with oral antibiotic for acute rhinosinusitis. METHODS: In this multicenter, double-blind, placebo-controlled study, 967 outpatients with computed tomographic scan-confirmed moderate to severe rhinosinusitis received amoxicillin/clavulanate potassium (Augmentin, GlaxoSmithKline, Research Triangle Park, NC) 875 mg, twice daily, for 21 days with adjunctive twice daily MFNS 200 microg, MFNS 400 microg, or placebo nasal spray. Patients recorded scores of six rhinosinusitis symptoms and any adverse events twice daily. Pre- and postcosyntropin-stimulation plasma cortisol levels were measured in a subset of patients at selected study sites. RESULTS: Treatment with MFNS 200 microg or 400 microg, twice daily, produced significantly greater improvements in total symptoms score (primary efficacy variable) day 1 to day 15 average (50% and 51%, respectively) than placebo (44%, P < or = 0.017). Both doses of MFNS produced significant total symptoms score improvement over placebo by day 4, and maintained efficacy over the entire 21-day study. Relief of individual symptoms showed a similar pattern. Both doses of MFNS were well tolerated, and adverse events were similar to that of placebo. Cosyntropin stimulation showed no evidence of hypothalamic-pituitary-adrenal axis suppression. CONCLUSIONS: As adjunctive therapy to oral antibiotic treatment, MFNS at doses of 200 microg or 400 microg, twice daily, was well tolerated and significantly more effective in reducing the symptoms of rhinosinusitis than antibiotic therapy alone.

Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness.

Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04 0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.