Regulatory Decision Summary for QNASL

The efficacy and safety of QNASL (beclomethasone dipropionate) Nasal Aerosol were evaluated in four Phase III randomized, double-blind, placebo-controlled, parallel group studies in patients with either seasonal allergic rhinitis (SAR) or perennial allergic rhinitis (PAR) of 2 or 6 weeks duration. Two studies were performed in adolescent and adult patients (12 years and older) treated with 320 µg/day: one study in patients with SAR and one study in patients with PAR. Two studies were performed in pediatric patients treated with 80 µg/day; one study in patients 6 to 11 years of age with SAR and one study in patients 4 to 11 years of age with PAR. The efficacy and safety of QNASL was supported by a 2-week dose ranging study in adult and adolescent patients with SAR and a 52 week study in adult and adolescent patients with PAR.

The primary efficacy endpoint in the clinical trials was the change from baseline in the average morning [that is (i.e.) AM] and evening (i.e., PM) subject-reported reflective total nasal symptom score (rTNSS) over the treatment period. A secondary endpoint for all of the clinical trials was the change from baseline in the average AM and PM subject-reported instantaneous TNSS (iTNSS). In the two pivotal clinical trials in adolescents and adults, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was another secondary endpoint.

In all studies, greater improvements in subject-reported rTNSS over the treatment period were observed compared to placebo and the treatment differences were clinically meaningful (>0.55) and statistically significant. The results for the secondary endpoints generally supported the results of the primary endpoint. In all studies, greater improvements in subject-reported iTNSS over the treatment period were seen with QNASL than with placebo and the difference was statistically significant. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was only assessed for adult subjects with impaired quality of life at baseline. The treatment difference from placebo was not clinically significant for the full adult study population (<0.5) with SAR, but was clinically and statistically significant for adult patients with PAR.

The results for the dose-ranging study and long-term study supported the results of the pivotal studies for the primary endpoint.

The benefit of QNASL is considered robust for the treatment of nasal symptoms of SAR and PAR in patients aged 6 and older. Only one trial included subjects as young as 4 years of age with PAR, therefore there is some uncertainty in the benefit for younger patients. However, the results of the analysis of rTNSS and iTNSS were similar between the two age groups. Therefore, it is acceptable that QNASL has benefit for the treatment of nasal symptoms for patients 4 years and older with SAR and PAR. There is uncertainty in the benefit to the quality of life as the disease-specific quality of life questionnaire, RQLQ, was only evaluated for adult subjects. Therefore, the effect on quality of life for patients aged 4-17 is not known.

QNASL did not have an effect on hypothalamic-pituitary-adrenal function, a known side effect of corticosteroids, which may be due to the low systemic bioavailability compared to oral inhalation of BDP.

The safety profile of QNASL was characterized mainly by local effects. The most comment adverse events in adolescent and adult patients treated with QNASL 320 µg/day were nasal discomfort, epistaxis, and headache. The most common adverse events in pediatric patients (4 to 11 years of age) treated with QNASL 80 µg/day were epistaxis, headache, pyrexia, upper respiratory tract infection, vomiting, nasopharyngitis, and cough. The majority of adverse events reported were of mild or moderate intensity. In the long-term clinical trials in adults and adolescents with PAR, there were four reports of nasal erosions and one nasal septum ulceration in patients treated with QNASL 320 µg/day. All of the potential adverse reactions have been addressed in the product monograph.

Overall, the benefit/risk balance for QNASL Nasal Aerosol is considered favourable for the recommended indication.