Bruce M. Prenner

Efficacy and Tolerability of Once-Daily 5mg Desloratadine, an H1-Receptor Antagonist, in Patients with Seasonal Allergic Rhinitis

ObjectiveTo evaluate the efficacy and tolerability of desloratadine 5mg once daily, a new, selective, H1-receptor antagonist, for the treatment of patients with seasonal allergic rhinitis (SAR) during the two major pollen seasons in the USA.DesignTwo multicentre, randomised, double-blind, placebo-controlled, parallel-group investigations in patients with SAR are reported, one conducted during the spring (172 and 174 patients in the desloratadine and placebo groups, respectively) and the other during the fall (164 patients each in the desloratadine and placebo groups) allergy season.Study ParticipantsPatients 12 years of age or older with clinically symptomatic SAR and a minimum 2-year history of SAR.InterventionsDesloratadine 5mg or placebo once daily for 14 days following a 1-week screening period.Main Outcome MeasuresThe primary efficacy assessment was the mean change from baseline in the average reflective am/pm total symptom score (TSS) averaged over the 2-week study period.ResultsIn both seasons, desloratadine 5mg once daily resulted in a significant improvement in TSS for patients with SAR (p < 0.01 and p = 0.02, respectively) over the 2-week study. Adverse events reported were mild to moderate in severity and similar to placebo. Assessment of sedation and ECG data revealed no clinically significant changes from baseline with desloratadine- or placebo-treated patients.ConclusionDesloratadine 5mg once daily was effective and well tolerated in the treatment of symptoms associated with SAR following the first dose of therapy and continuing for the 2-week duration of the study during both the spring and fall allergy seasons.

Safety of house dust mite sublingual immunotherapy standardized quality tablet in children allergic to house dust mites

BACKGROUND Sublingual immunotherapy (SLIT) tablets could be an important alternative to subcutaneous immunotherapy for house dust mite (HDM) allergy in children. OBJECTIVE To characterize the safety, tolerability, and duration of local adverse events (AEs) of an HDM SLIT tablet (MK-8237; Merck, ALK Abellò, and Torii) in North American children 12 to 17 years old with HDM allergic rhinitis with and without conjunctivitis and with or without asthma. METHODS In this phase 1, multicenter, double-blinded, randomized trial (NCT01678807), children received placebo, HDM SLIT tablet 6 standardized quality (SQ) HDM, or 12 SQ-HDM once daily for 28 days. The primary end point was the proportion of subjects with treatment-emergent AEs receiving active treatment vs placebo. The secondary end point was the proportion of subjects who discontinued owing to AEs. RESULTS In total 195 subjects were randomized. The 2 HDM SLIT tablet doses were well tolerated. No anaphylactic reactions, systemic allergic reactions, AEs requiring epinephrine, serious AEs, or local swellings in the mouth or throat assessed as severe were reported. The proportion of subjects with treatment-emergent AEs was 54% with 6 SQ-HDM and 57% with 12 SQ-HDM (nonsignificant vs 43% with placebo). Local AEs were the most commonly reported treatment-emergent AEs. On day 1, the median duration of individual local AEs ranged from 1 to 43 minutes. The proportion of subjects who discontinued owing to AEs was 0%, 6.2%, and 6.2%, and who experienced treatment-related AEs was 25%, 45%, and 52% for the placebo, 6 SQ-HDM, and 12 SQ-HDM groups, respectively. CONCLUSION The 6 and 12 SQ-HDM doses of the HDM SLIT tablet MK-8237 were well tolerated, and local AEs were of short duration. TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT01678807.

Mometasone furoate nasal spray reduces the ocular symptoms of seasonal allergic rhinitis

BACKGROUND Mometasone furoate nasal spray (MFNS), a potent intranasal corticosteroid with proved efficacy in relieving nasal allergic rhinitis symptoms, has demonstrated effectiveness in improving ocular symptoms associated with seasonal allergic rhinitis (SAR) in retrospective analyses. OBJECTIVE We sought to evaluate prospectively the efficacy of MFNS in reducing total ocular symptom scores (TOSSs) and individual ocular symptoms in subjects with SAR. METHODS Subjects 12 years or older (n = 429) with moderate-to-severe baseline symptoms were randomized to MFNS, 200 microg once daily, or placebo in this 15-day, double-blind, parallel-group study. Subjects evaluated morning instantaneous TOSSs and daily reflective TOSSs, total nasal symptom scores (TNSSs; both instantaneous TNSSs and reflective TNSSs, respectively), and individual ocular and nasal symptoms. Mean changes from baseline averaged over days 2 to 15 (instantaneous) and days 1 to 15 (reflective) were calculated. Quality of life was assessed by using the Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS MFNS treatment yielded significant reductions from baseline versus placebo in instantaneous TOSSs (-0.34, P = .026, coprimary end point), instantaneous TNSSs (-0.88, P < .001, coprimary end point), reflective TOSSs (-0.44, P = .005), and reflective TNSSs (-1.06, P < .001). Significant decreases in all individual reflective ocular symptoms and instantaneous eye itching/burning and eye watering/tearing were observed for MFNS versus placebo (P < .05). Numeric improvements in instantaneous eye redness were seen but did not reach statistical significance. Improvements in Rhinoconjunctivitis Quality of Life Questionnaire total scores and individual symptom domains were achieved with MFNS treatment versus placebo (P < .001). MFNS was well tolerated. CONCLUSION This prospective study demonstrates that MFNS significantly reduces ocular symptoms in subjects with SAR.

Mometasone furoate nasal spray plus oxymetazoline nasal spray: short-term efficacy and safety in seasonal allergic rhinitis.

Background Allergic rhinitis (AR) and associated congestion adversely affect patients’ lives. The intranasal corticosteroid mometasone furoate nasal spray (MFNS) is effective for AR symptoms including nasal congestion, and the intranasal decongestant oxymetazoline (OXY) is effective against nasal congestion, but the combination has not been fully studied. This study was designed to assess the efficacy of the combination of MFNS and OXY for the relief of seasonal allergic rhinitis (SAR) symptoms. Methods This phase 2 controlled clinical trial randomized adolescent and adult subjects (≥12 years; 2-year SAR) to MFNS q.d. (200 μg) + 3 sprays/nostril of OXY 0.05% (MFNS + OXY3); MFNS q.d. + 1 spray/nostril of OXY (MFNS + OXY1); MFNS q.d.; OXY b.i.d.; or placebo for 15 days, with 1-week follow-up. Coprimary end points were change from baseline in morning/evening (A.M./P.M.) instantaneous (NOW) total nasal symptom score (TNSS) over days 1–15 and AUC (AUC[0–4 hr]) change from baseline in day 1 congestion. Results In 705 subjects, both combinations reduced A.M./P.M. NOW TNSS over days 1–15 significantly more than OXY b.i.d. or placebo (p ≤ 0.002). Mean standardized AUC(0–4 hr) day 1 congestion change from baseline was significantly greater in combination and OXY b.i.d. groups (MFNS + OXY3, −0.92; MFNS + OXY1, −0.80; OXY b.i.d., −1.06) versus placebo (–0.57) and MFNS q.d. (–0.63). Combinations and MFNS q.d. were significantly effective for A.M./P.M. NOW TNSS over each weekly period; OXY b.i.d. was superior to placebo in week 1. Adverse events (AEs) were few and similar across treatments; one MFNS q.d. and one placebo subject experienced a serious AE, with neither considered treatment related. Conclusion Combining MFNS with OXY relieves SAR symptoms, including congestion, with faster onset of action than MFNS q.d. and better sustained efficacy than OXY b.i.d.

Asthma symptoms and airway hyperresponsiveness are lower during treatment with nedocromil sodium than during treatment with regular inhaled albuterol

In a double-blind, double-dummy, multicenter study, 212 patients with asthma whose symptoms were not controlled by as-needed use of inhaled bronchodilators were randomized to receive either 4 mg of nedocromil sodium or 180 micrograms of albuterol four times daily for 12 weeks. Asthma symptom scores (daytime asthma, nighttime asthma, morning chest tightness, and cough) and peak expiratory flow rate were recorded daily on diary cards. Bronchial hyperresponsiveness was assessed by changes in diurnal variation in peak expiratory flow rate and by methacholine inhalation challenge. Statistically significant differences were found between groups favoring nedocromil sodium for relief of day and nighttime asthma and morning chest tightness. Patients treated with nedocromil sodium also had significantly lower diurnal variation in peak expiratory flow rate compared with patients treated with albuterol. Compared with patients treated with albuterol, patients treated with nedocromil sodium showed a greater improvement in cough and a decreased sensitivity to methacholine challenge. Patients in both groups reduced their as-needed albuterol use. Regular treatment with nedocromil sodium therefore led to greater asthma symptom control and reduced bronchial responsiveness compared with regular treatment with albuterol. The study also showed that more frequent use of a beta 2-agonist (for symptom relief or not) did not improve asthma control. Both drugs were well tolerated.

Efficacy, safety, and optimal dose selection of beclomethasone dipropionate nasal aerosol for seasonal allergic rhinitis in adolescents and adults.

Abstract Objective: Some patients with allergic rhinitis (AR) may prefer nonaqueous intranasal corticosteroid aerosols because of unwanted attributes of aqueous formulations. The mandatory removal of chlorofluorocarbon-propelled nonaqueous aerosols from the market limited available treatment options. To fulfill this unmet need, a nonaqueous, hydrofluoroalkane-propelled beclomethasone dipropionate (BDP) nasal aerosol was developed and approved for treatment of AR nasal symptoms. As part of the development program, this dose-ranging study evaluated three doses of BDP nasal aerosol to determine the optimally safe and effective dose for adolescent and adult patients (≥12 years old) with seasonal AR (SAR). Methods: After a 7 to 21 day placebo run-in period, eligible patients with SAR were randomly assigned to once-daily BDP nasal aerosol 80 µg, 160 µg, 320 µg, or placebo. The primary endpoint was the change from baseline in average a.m. and p.m. patient-reported reflective total nasal symptom scores (rTNSS) over 2 weeks. Safety and tolerability were also assessed. A potential study limitation could be lack of objective assessment of AR symptoms. Results: Significant improvements were seen in average a.m. and p.m. rTNSS (least squares [LS] mean treatment difference, −0.63; 95% CI: −1.13, −0.13; p = 0.013) as well as in average a.m. and p.m. instantaneous TNSS (iTNSS; LS mean treatment difference, −0.60; 95% CI: −1.09, −0.11; p = 0.016) with BDP nasal aerosol 320 µg/day compared with placebo. Although there were numerical improvements from baseline in patient-reported rTNSS and iTNSS with BDP nasal aerosol 80 µg and 160 µg, these doses did not achieve statistical significance compared with placebo. BDP nonaqueous nasal aerosol was well tolerated at all doses tested, with a safety profile comparable to that of placebo. Conclusions: These data indicate that 320 µg/day of BDP nasal aerosol is the optimally safe and effective dose for the treatment of SAR in adolescent and adult patients. Trial registration NCT: #NCT00854360.

Once-Daily Cetirizine Is Safe and Effective for Children with Allergic Rhinitis with and without Intermittent Asthma

The prevalence of seasonal allergic rhinitis among 1 to 12 year olds is between 10% and 20%. Cetirizine is a selective, once-daily H1 antagonist approved for the treatment of seasonal allergic rhinitis, perennial allergic rhinitis, and chronic idiopathic urticaria in adults and children 2 years and older, and was recently approved for the treatment of perennial allergic rhinitis and chronic urticaria in children down to 6 months of age. This randomized, multicenter, double-blind, placebo-controlled study enrolled 172 children with seasonal allergic rhinitis, including a large subgroup with concomitant asthma. Cetirizine syrup or placebo were administered for 2 weeks. Cetirizine 10 mg once daily provided significant relief from symptoms of seasonal allergic rhinitis, both in children with and without concomitant asthma. Among subjects with asthma, the frequency and severity of asthma symptoms were similar between the cetirizine and placebo groups. Cetirizine caused no adverse effects on pulmonary function ...