Rhinitis, Allergic, Perennial
April 3, 2017
Glenmark Pharmaceuticals issued results of a phase III trial of GSP 301, an investigational fixed-dose combination of mometasone furoate (25mcg) and olopatadine hydrochloride (665mcg), administered twice-daily as a nasal spray being studied for the treatment of seasonal allergic rhinitis. This U.S.-based trial was a four-arm, double-blind, randomized, parallel group, active and placebo-controlled study that enrolled 1,176 adults and adolescents 12 years of age and older for 14 days of twice daily treatment with GSP 301, mometasone (a corticosteroid), olopatadine (a histamine H1-receptor agonist) or placebo. All trial arms utilized the same vehicle and nasal spray delivery system. The primary endpoint was change from baseline in average morning and evening patient-reported 12-hour reflective Total Nasal Symptom Score (rTNSS). Secondary endpoints include safety and tolerability. In the trial, treatment with GSP 301 demonstrated statistically significant and clinically meaningful improvement from baseline in average morning and evening patient-reported rTNSS, compared to placebo (p<0.001), olopatadine (p=0.028) and mometasone (p=0.019). All investigational treatments administered in the trial were well-tolerated and showed no meaningful differences in reported adverse events (AEs) across study arms. The most common AE occurring in at least 2% of patients was dysgeusia.
March 17, 2014
Merck released results from phase IIb trials
evaluating two doses of its investigational
house dust mite sublingual immunotherapy
tablet MK-8237. In the double-blind,
single-site, phase IIb study, 124 adults, 18
years of age or older, with house dust mite-induced
allergic rhinitis, with or without
conjunctivitis, were randomized to receive
six Development Units (DU) (n=41) or 12
DU (n=42) of MK-8237 sublingual tablets
once daily for 24 weeks or placebo (n=41).
Sensitivity to house dust mite allergen was
determined by specific IgE testing. Patients
with unstable uncontrolled/partially
controlled or severe asthma were excluded
from the study, as were patients with forced
expiratory volume in 1 second (FEV1). Both
doses of MK-8237 showed a significant
dose- and time-dependent reduction in
average TNSS over the last four hours of the
chamber challenge at week 24 of treatment
compared to placebo (-27%=6 DU, -49%=12
DU). The most common adverse events (incidence
= 5%) occurring in patients receiving
MK-8237 6 DU, 12 DU or placebo, respectively,
were throat irritation (34%, 52%, 0%),
mouth edema (24%, 24%, 0%), lip swelling
(5%, 17%, 2%), oral pruritus (15%, 14%,
0%), dyspepsia (2%, 10%, 0%), ear pruritus
(0%, 7%, 0%), swollen tongue (0%, 5%, 0%),
oropharyngeal swelling (0%, 5%, 0%) and
pharyngeal edema (2%, 5%, 0%). There were
no local swellings of severe intensity and no
serious adverse events reported in patients
treated with MK-8237. A phase III study of
MK-8237 in adolescents and adults with
house dust mite-induced allergic rhinitis
currently is screening patients.
May 30, 2011
Actelion issued results from a phase II trial of their CRTH2 receptor antagonist for the treatment of seasonal allergic rhinitis. This double-blind, placebo-controlled, randomized study enrolled 579 subjects with seasonal allergic rhinitis due to mountain cedar pollen. The subjects were treated for two weeks with various doses of the CRTH2 antagonist or placebo. The primary endpoint was to demonstrate efficacy versus placebo on the mean change from baseline in Daytime Nasal Symptom Score over the entire treatment period. The primary endpoint was reached with statistical significance (p<0.05). The treatment was well tolerated across all treatment groups and no serious adverse events were reported.
May 9, 2011
ISTA Pharmaceuticals issued results from a phase II trial of bepotastine besilate nasal spray for seasonal allergic rhinitis. This randomized, multi-center, double-masked, placebo-controlled, dose-ranging trial enrolled 600 subjects with allergic rhinitis caused by Mountain Cedar pollen. The subjects received one of three concentrations of bepotastine besilate nasal spray or placebo twice a day for two weeks. All three concentrations of bepotastine besilate nasal spray showed statistically significant improvements compared to placebo for nasal and ocular symptoms following exposure to Mountain Cedar pollen during the peak season for this allergen. These improvements were seen on day one of therapy and were sustained through the two-week treatment period. Safety data demonstrated bepotastine besilate was well-tolerated as a nasal spray, with an adverse event profile similar to placebo.
February 14, 2011
Teva released positive results from a phase III trial of Qnaze, their nasal aerosol corticosteroid for perennial allergic rhinitis. The randomized, double-blind, placebo-controlled, parallel-group clinical study enrolled 470 subjects, aged 12 years and older, who received Qnaze nasal aerosol 320 mcg or placebo once-daily for six weeks. The primary endpoint, the change from baseline in the average morning and evening subject-reported reflective Total Nasal Symptom Score (rTNSS), was reached with statistical significance over placebo (p<0.001). The change in instantaneous TNSS (iTNSS), a secondary endpoint, was also significantly greater versus placebo. In addition, for both of these measures, all four individual nasal symptom scores of runny nose, nasal congestion, nasal itching and sneezing demonstrated significant improvement versus placebo. Qnaze was well tolerated.
October 11, 2010
ISTA Pharmaceuticals reported positive results from a phase I/II trial of bepotastine besilate nasal spray for the treatment of seasonal allergic rhinitis. This double-masked, randomized, placebo-controlled, parallel-group study enrolled 82 subjects in Canada. The subjects were exposed on multiple occasions in an Environmental Exposure Chamber to a high aerosol concentration of a common seasonal allergen to which they were sensitive. They graded their individual symptoms at select time intervals prior to and following a single dose or one week of dosing with one of three bepotastine besilate nasal spray doses or placebo. The highest two concentrations of bepotatine besilate nasal spray tested showed statistically significant improvement compared to placebo in reducing total nasal symptoms. These reports were consistent for both instantaneous and reflective experiences of their total nasal symptoms. Statistically significant improvements also were seen for all individual nasal symptoms, with the most rapid improvement seen for drug-related reductions in sneezing and nasal itching. Adverse events were similar across all treatment groups.
May 26, 2008
Allergy Therapeutics released positive results from a phase III trial of Pollinex Quattro for the treatment of seasonal allergic rhino-conjunctivitis caused by grass allergy. This double-blind placebo-controlled study, dubbed G301, enrolled 1,028 subjects in the United States, Canada and Europe. The subjects received four injections of either Pollinex Quattro or placebo treatment over three weeks prior to the 2007 grass pollen season. They then recorded rhino-conjunctivitis symptoms and medication intake over the course of the pollen season from May to September. The primary endpoint was the difference in combined symptom plus medication score between active and placebo treatment over the four peak pollen weeks of the season. The primary endpoint was reached, with a 13.3% improvement in the Pollinex Quattro group over placebo (p = 0.0038) in the Intent To Treat population and a 26.9% improvement over placebo in the prospectively defined patient population (p = 0.0031). Treatment was determined to be safe and well tolerated. Based on the results Allergy Therapeutics plans to file an MAA in the EU in quarter one of 2009.
April 28, 2008
Inspire reported negative results from a phase III trial of epinastine nasal spray for the treatment of seasonal allergic rhinitis (SAR). This fourteen-day, randomized, double-blind trial enrolled seven hundred and ninety eight subjects with documented SAR during mountain cedar season in south central Texas. The subjects received epinastine (0.10% and 0.15%) or placebo. The primary efficacy endpoint was average change from baseline for the reflective Total Nasal Symptom Score (TNSS). The study failed to achieve statistical significance compared to placebo on this endpoint. Based on the results Inspire has decided to discontinue the development of epinastine nasal spray.
August 13, 2007
Cobalis announced additional positive results from a phase III trial of PreHistin for the treatment of seasonal allergic rhinitis. These parallel, randomized, double-blind trials enrolled 1,551 subjects in the US. Subjects received either a placebo or a 3.3-mg sublingual dosage of PreHistin twice daily for three weeks prior to the onset of the ragweed allergy season and for an additional three weeks into the allergy season. Results showed a significant average increase of more than 250% in post-treatment blood serum cobalamin (Vitamin B12) levels across the two PreHistin-treated groups compared with essentially no B12 level increase in placebo-treated groups. In the first trial, the mean pre-treatment B-12 levels (measured as pg/mL) for the PreHistin and placebo groups, respectively, were 554.60 and 521.90 and the mean post-treatment B-12 levels were 2050.50 and 526.50, for a 269.73% versus 0.88% change. In the second trial, the mean pre-treatment B-12 levels for the PreHistin and placebo groups, respectively, were 581.58 and 508.54 and the mean post-treatment B-12 levels were 1938.31 and 514.70, for a 233.28% versus a 1.21% change. Cobalis plans to pursue US regulatory approval.
July 16, 2007
Cobalis released mixed results from two phase III trials of PreHistin for the treatment of seasonal allergic rhinitis. These parallel, randomized, double-blind trials enrolled 1,551 subjects in the US. Subjects received either a placebo or a 3.3-mg sublingual dosage of PreHistin twice daily for three weeks prior to the onset of the ragweed allergy season and for an additional three weeks into the allergy season. The primary endpoint was the difference in the mean reduction on the Total Nasal Symptom Score (TNSS) observed between the placebo and PreHistin over the fourth, fifth and sixth weeks of the studies. PreHistin did not achieve statistically significant differences from placebo in this primary endpoint. However, the TNSS data for placebo-treated subjects was far lower than would be expected for this population. The very low symptom levels reported in both the placebo and PreHistin groups were determined to be likely due to low pollen counts in the regions where the trials were conducted. Based on the results, Cobalis plans to pursue FDA approval of PreHistin.
December 5, 2005
Rigel Pharmaceuticals issued negative results of a phase II study of R112, for the treatment of allergic rhinitis. Trial data failed to meet their primary endpoint, producing no significant reduction in symptom severity score on the total nasal symptom severity diagnostic scale, compared to placebo. Subjects receiving treatment with an approved control drug did experience such a reduction. This randomized, double-blind, controlled study enrolled 396 patients across 25 US sites, who received the drug, approved treatment with beclomethasone, or placebo twice daily for 7 days.
October 31, 2005
Cobalis issued positive final results of a phase III trial of PreHistin, for the treatment of allergic rhinitis. Results from the study demonstrated a statistically significant reduction in symptom severity score for both mean values for weeks 4-6 (p=0.0262) and the week 6 final analysis (p=0.0416), compared to baseline. Efficacy was also demonstrated in comparison to placebo for both values (p=0.0028, p=0.0048, respectively). The magnitude of difference in score, 1.31 points, represented a clinically significant difference. This randomized, double-blind, placebo-controlled, multi-center study enrolled 714 subjects across 8 US sites, who received the drug or placebo for 6 weeks during peak allergy season. These data served to support the company's ongoing phase III development program and eventual NDA submission.
September 26, 2005
Evolutec has issued positive results of a phase II trial of rEV131, their recombinant immunomodulatory drug under investigation for the treatment of seasonal allergic rhinitis. Results from the study met their primary efficacy endpoint, producing a significant reduction in the mean sum of symptom scores at 15 minutes (p<0.05). Symptom relief was seen to be dose-dependent, and no serious adverse events or tolerability concerns were raised. This placebo-controlled, single-dose, dose- ranging allergen-challenge study enrolled 112 patients across 2 sites in San Antonio, Texas, who were randomized into one of four 20-patient single-dose cohorts (16 active, 4 placebo), or a fifth cohort of 32 subjects at the optimum dose (16 active, 16 placebo). Based on these results, the company announced plans to initiate a multiple-dose phase II study of the drug in the near future.
July 11, 2005
Corixa has announced positive results of a phase I trial of CRX-675, their toll-like receptor 4 agonist under investigation for the treatment of allergic rhinitis. Results from the study met their primary safety endpoints, with no serious adverse events reported and an overall positive tolerability profile, which was similar to placebo. Exploratory efficacy data indicated that a 100 mcg dose of the drug yielded trends towards reduction in nasal symptoms following ragweed challenge at both 1 and 14 days. Neither a dose-response relationship nor a trend towards improvement in nasal congestion was not noted. This randomized, blinded, placebo-controlled study enrolled 64 subjects, who were randomized to receive one of 4 single escalating doses of the drug (2 mcg, 20 mcg, 100 mcg or 200 mcg; n=12/group) or placebo (n=16). The company announced plans to initiate safety and efficacy studies by the end of 2005 or early 2006.
February 9, 2004
Intranasal Technology reported results from a clinical trial investigating their intranasal hydromorphone, a narcotic and analgesic for the treatment of allergic rhinitis. Results showed median times to peak plasma concentrations of 10 minutes in the hydromorphone IV group and 15 minutes in the hydromorphone intranasally group. Data showed a statistically significant delay in time to peak in subjects treated with fluticasone propionate. The open-label, randomized, three-way crossover, inpatient study enrolled 12 subjects with perennial or seasonal rhinitis. Subjects were randomized to receive single doses of hydromorphone HCl 2.0 mg intravenously, intranasally with no pretreatment, or intranasally after 6 days of pretreatment with fluticasone propionate. Results were reported in the January issue of Pharmacotherapy.
August 19, 2002
Inspire Pharmaceuticals announced positive results of a phase II trial with INS37217 Intranasal, a P2Y2 agonist, for the treatment of perennial allergic rhinitis (PAR). The randomized, parallel-group, double-blind study, which involved 59 subjects with chronic rhinitis, compared the effects of three doses of INS37217 Intranasal to placebo. Results showed that subjects treated with INS37217 Intranasal demonstrated statistically significant improvement in PAR symptoms as compared to placebo across multiple days and multiple doses. In addition, the mid-dose treatment group showed statistically significant improvement compared to placebo in the mean total nasal symptom score at the end of the study. This result is consistent with phase I results which also indicated the most robust effects in the mid-dose group.