Nasal Carbon Dioxide Used As Needed in the Symptomatic Treatment of Seasonal Allergic Rhinitis.

BACKGROUND: Nasal, noninhaled carbon dioxide (CO2) was shown to be effective for the treatment of symptoms of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis in single application studies. OBJECTIVE: To assess the efficacy of as-needed treatment with nasal, noninhaled CO2 in patients with SAR. METHODS: Fifty-six ragweed-allergic patients were enrolled at 3 sites in this study. After a 3- to 7-day run-in, 32 eligible patients who had an instantaneous total nasal symptom score of 8 or more out of a maximum of 12 in at least 2 SAR episodes per day were randomized to the CO2 group (n = 19) or to the placebo group (n = 13). A 10-second/nostril application was used as needed for 14 days (maximum 6 times/d). Patients evaluated their symptoms before and 30 minutes after each application. All symptoms were scored on a 0 to 3 scale. RESULTS: Analysis of all treated episodes (CO2 = 816, placebo = 516) showed a statistically significant beneficial change in total nasal symptom score from baseline (effect size = -0.51; P < .001). The effect size was larger with more severe baseline symptoms (baseline severities of ≥6 = -0.98; ≥8 = -1.14; and ≥10 = -1.61; all P < .001). CO2 was well tolerated, with transient nasal discomfort as the most common adverse event reported. There were no serious adverse events, serious adverse device effects, or early discontinuations. CONCLUSIONS: Nasal, noninhaled CO2 is effective for the as-needed treatment of SAR symptoms. The effect is rapid and the effect size is large. It represents a novel potential option for the as-needed treatment of rhinitis symptoms.

Onset of action of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg in subjects aged 12 years with moderate to severe seasonal allergic rhinitis: a pooled analysis of two single-dose, randomized, double-blind, placebo-controlled allergen exposure unit studies.

BACKGROUND: The onset of action of antihistamine-decongestant combinations is an important factor in the treatment of subjects with seasonal allergic rhinitis (SAR). OBJECTIVE: This was a pooled analysis of 2 published studies with identical designs investigating the onset of action of the combination of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg (FEX60/PSE120) in subjects with moderate to severe SAR. METHODS: Subjects aged 12 years received single doses of FEX60/PSE120 or placebo in 2 randomized, double-blind, placebo-controlled, parallel-group, allergen exposure unit studies and recorded their SAR symptoms on diary cards before dosing, at 15-minute intervals for 2 hours after dosing, and at 30-minute intervals for the next 4 hours. The primary efficacy end point was onset of action, assessed in terms of absolute change in the major symptom complex (MSC) score, which was the sum of scores for the individual symptoms of stuffy nose, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, and sneezing. Secondary end points included the absolute and percent change in the total symptom complex (TSC) score (the sum of the MSC score plus the scores for nose blowing, sniffles, postnasal drip, and cough) and individual symptom scores. Treatment-emergent adverse events (TEAEs) were recorded. Analyses were performed on the modified intention-to-treat (mITT) population, which included all subjects who were randomized to treatment and took the single dose of study medication according to the protocol. RESULTS: A total of 1693 subjects were screened in the 2 studies, and 786 were randomized (298 in study 1, 488 in study 2). Two subjects withdrew from study 2; therefore, the mITT population consisted of 784 subjects. Subjects' mean age was 33.4 years, and 64.4% were female. The onset of action of FEX60/PSE120 was 45 minutes; the least squares mean (SD) treatment difference in the change from baseline in absolute MSC score was 0.8 (0.31) (95% CI, 0.2-1.4; P = 0.008). All subsequent changes from baseline in MSC scores were statistically significant for FEX60/PSE120 compared with placebo (P < 0.001). The absolute and percent change in TSC score and the percent change in MSC score were significantly decreased at all time points from 45 minutes after dosing for FEX60/PSE120 compared with placebo (all, P < 0.05). Individual symptoms (mean of hours 1 to 5) also were significantly improved with FEX60/PSE120 compared with placebo (all, P < 0.05). TEAEs were reported by 2.3% (9/391) and 4.3% (17/393) of subjects receiving FEX60/PSE120 and placebo, respectively. The most commonly occurring TEAS in the FEX60/PSE120 and placebo groups was somnolence (n = 4 and n = 6, respectively). CONCLUSION: In this pooled analysis of 2 allergen exposure unit studies, FEX60/PSE120 had an onset of action of 45 minutes and a sustained effect throughout the 6-hour study period in subjects with moderate to severe SAR.

Efficacy of fexofenadine in the prophylactic control of cat allergen-induced allergic rhinitis.

BACKGROUND: To date, it is unknown whether fexofenadine mitigates the worsening of symptoms induced by the cat allergen Felis domesticus allergen 1. OBJECTIVE: To determine the effects of a single dose of fexofenadine hydrochloride, 180 mg, in preventing and controlling cat allergen-induced allergic rhinitis symptoms using the cat room challenge model. METHODS: This single-center, randomized, double-blind, placebo-controlled, 2-way crossover study consisted of a screening visit, 1 or 2 qualifying visits, and 2 treatment periods separated by a mean +/- SD washout period of 14 +/- 3 days. Patients were randomized to treatment sequence 1 (placebo followed by fexofenadine) or sequence 2 (fexofenadine followed by placebo). Baseline end points were obtained before study drug administration, and allergen challenges were initiated 1 1/2 hours after dosing. The primary end point was the change from predose baseline in the total symptom score (sum of rhinorrhea, itchy nose/palate/ throat, sneezing, and itchy/watery/red eyes) after 30 minutes of allergen exposure compared with placebo. RESULTS: Of 211 patients screened, 66 were randomized and 63 completed the study. Mean change in the total symptom score from predose baseline was significantly less with fexofenadine compared with placebo 30 minutes after initiation of the cat allergen challenge (2 hours after dosing) (P = .03). The overall incidence of treatment-emergent adverse events was low and comparable for both groups. CONCLUSION: Prophylactic treatment with a single dose of fexofenadine hydrochloride, 180 mg, significantly mitigated the worsening of allergic rhinitis symptoms induced by exposure to cat allergen compared with placebo use.

An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment.

BACKGROUND: R112 inhibits Syk kinase, a transducer of signaling through the Fcepsilon receptor of mast cells, blocking mast cell responses to allergic stimuli. OBJECTIVE: Examine the efficacy and safety of intranasal R112 in volunteers with symptomatic seasonal allergic rhinitis compared with a placebo in a park setting. METHODS: In this double-blind, placebo-controlled study of 319 volunteers with seasonal allergic rhinitis, 160 were randomized to intranasal R112 and 159 to a vehicle control during 2 days at 2 separate locations in spring 2004. Subjects were evaluated for symptoms of allergic rhinitis (i.e., sneezes, runny nose/sniffles, itchy nose, stuffy nose) on the basis of a possible maximum score of 32 for the Global Symptom Complex (GSC) scale. The primary outcome evaluated was the difference in the reduction in GSC (area under the curve over a period of 8 hours) from baseline between R112 and vehicle placebo. RESULTS: At baseline, the combined GSC was approximately 18/32 and equal between treatment groups. After 8 hours (dosing 3 mg/nostril every 4 hours x 2), R112 significantly reduced the GSC compared with placebo (7 vs 5.4 units, respectively; P = .0005). Each individual symptom combined to form the GSC was also significantly improved in the R112 group compared with control ( P < .05). As early as 45 minutes after dosing, R112 showed a significant improvement in symptoms over placebo, and the duration of action exceeded 4 hours. Adverse effects were indistinguishable between the groups and clinically insignificant. CONCLUSION: Intranasal R112 was effective in this park study and is a promising new treatment for seasonal allergic rhinitis.

Fexofenadine HCl 60 mg/ pseudoephedrine HCl 120 mg has a 60-minute onset of action in the treatment of seasonal allergic rhinitis symptoms, as assessed in an allergen exposure unit.

Although antihistamine-decongestant combinations are frequently used for allergic rhinitis, published data about the onset of action of these combination agents are limited. This randomized, double-blind, placebo-controlled, parallel-group study investigated the onset of action, efficacy, and safety of fexofenadine HCl 60 mg/pseudoephedrine HCl 120 mg or placebo in patients with moderate-to-severe seasonal allergic rhinitis in an allergen exposure unit. Assessments included major symptom complex (MSC) score (sum of sneezing, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, and stuffy nose), and total symptom complex (TSC) score (MSC symptoms plus nose blows, sniffles, postnasal drip, and cough). Onset of action was defined as the first time that two consecutive, statistically significant absolute changes in MSC scores from baseline were achieved for study drug relative to placebo. The onset of action for the combination was 60 minutes (mean absolute MSC change from baseline: -6.9 +/- 0.3 for the combination compared with -5.9 +/- 0.3 for placebo from a baseline of 17.0 and 16.8, respectively; p < 0.05) for the modified intention-to-treat population (n = 486). Reductions in absolute MSC scores were significantly greater with the combination than placebo at all subsequent time points (p < 0.01). The combination resulted in significantly greater reductions compared with placebo for percent MSC, absolute TSC, and percent TSC scores at 60 minutes postdose (all p < 0.05) and throughout the study (all p < 0.05). The incidence of adverse events was 1.6 and 3.3% for the combination and placebo, respectively. In conclusion, fexofenadine HCl 60 mg/pseudoephedrine HCl 120 mg is effective in the treatment of patients with moderate-to-severe seasonal AR, with an onset of action of 60 minutes and a good safety profile.

Onset of action, efficacy, and safety of fexofenadine 60 mg/pseudoephedrine 120 mg versus placebo in the Atlanta allergen exposure unit.

BACKGROUND: Second-generation antihistamine-decongestant combinations are often used to treat seasonal allergies. However, onset of action and efficacy data for these agents in a controlled setting are limited. OBJECTIVE: Determine onset of action of fexofenadine-pseudoephedrine (Allegra-D, Aventis, Bridgewater, NJ) for treating moderate-to-severe seasonal allergies in an allergen exposure unit. METHODS: This single-dose, double-blind, placebo-controlled study was conducted during the fall ragweed allergy season. Qualifying subjects attended one to two priming visits; those with sufficient symptom scores returned for treatment and were initially exposed to ragweed pollen for 90 minutes. Symptomatic subjects received fexofenadine-pseudoephedrine or placebo and recorded symptoms for 6 hours postdose. Efficacy variables were major symptom complex (MSC; sneezes, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, stuffy nose), total symptom complex (nose blows, sniffles, postnasal drip, cough, plus all MSC symptoms), and all individual symptoms as well as headache. Onset of action for each efficacy variable was calculated as the earliest time at which a consistent, significant decrease was seen for fexofenadine-pseudoephedrine versus placebo. RESULTS: Of 571 screened subjects, 298 were randomized. Onset of relief for fexofenadine-pseudoephedrine (n = 148) was 45 minutes postdose (MSC, P = 0.0127; total symptom complex, P = 0.0380). All individual symptoms were reduced to a greater extent with fexofenadine-pseudoephedrine than with placebo (P < 0.05, not adjusted for multiple comparisons). Decrease in headache with fexofenadine-pseudoephedrine versus placebo began 45 minutes postdose (P = 0.0425). Incidence of treatment-related adverse events was 1.4% for fexofenadine-pseudoephedrine and 3.3% for placebo. CONCLUSIONS: Fexofenadine-pseudoephedrine was safe and effective in treating a broad range of allergy symptoms, with a rapid onset of action at 45 minutes.