Mometasone furoate

Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured by spirometry.

A TEAE is any adverse event that started on or after the time of the first inhalation of study drug but not later than 7 days (30 days in the case of a SAE) after the last administration. A SAE is described as any adverse event that leads to death, is life-threatening, results in persistent or significant disability/incapacity, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event which is medically significant.

Patients were required to record a 12 hour "reflective" score twice a day approximately 12 hours apart. For the rTNSS patients were asked to "look back" or "reflect" on their severity of nasal symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline rTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as "mean baseline rTNSS" - "mean post-randomization rTNSS". A positive change from baseline in rTNSS is considered a favorable outcome.

Patients were required to record a 12 hour "reflective" score twice a day approximately 12 hours apart. For the rTNSS patients were asked to "look back" or "reflect" on their severity of nasal symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline rTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as "mean baseline rTNSS" - "mean post-randomization rTNSS". A positive change from baseline in rTNSS is considered a favorable outcome.

Mometasone furoate plasma concentrations were determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Cmax of mometasone furoate was determined with Phoenix WinNonlin (Version 8.0 or higher). A correction factor was applied to MF pharmacokinetic parameters to consider the first-dose effect that is based on the fact that the participants in this study received a single dose from single unused (unprimed) C1 and TH devices. Unprimed devices are not coated with the formulation, and therefore may lead to lower fine particle mass (FPM) and delivered dose compared to later doses actuated from the device throughout its use time. The first-dose correction factor (FPMprimed (MF) / FPMunprimed (MF)) for MF delivered via TH was 1.26 and for MF delivered via C1 it was 1.62.

AUC0-6h of mometasone furoate was determined using non-compartment methods with Phoenix WinNonlin (Version 8.0 or higher). The linear trapezoidal rule was used for AUC0-6h calculation. A correction factor was applied to MF pharmacokinetic parameters to consider the first-dose effect that is based on the fact that the participants in this study received a single dose from single unused (unprimed) C1 and TH devices. Unprimed devices are not coated with the formulation, and therefore may lead to lower fine particle mass (FPM) and delivered dose compared to later doses actuated from the device throughout its use time. The first-dose correction factor (FPMprimed (MF) / FPMunprimed (MF)) for MF delivered via TH was 1.26 and for MF delivered via C1 it was 1.62.

Spirometry is conducted according to the global standard. Trough FEV1 is defined as the average of the 23 hour 10 minute and 23 hour 45 minute post dose FEV1 readings.

Forced Expiratory Volume in 1 second (FEV1) was measured via spirometry conducted according to internationally accepted standards. Measurements were taken on day 29 after treatment.

For FEV1 AUC(0-12h) the trapezoidal rule was applied using planned time measurements to calculate the AUC up to and including the last measurement recorded before intake of rescue medication. The AUC was standardized by dividing by the length of time for which measurements of FEV1 were included in the calculation of the AUC thus adjusting for subjects who were unable to complete the measurements during the 12-hour observation period and without inhaling rescue medication. The unit of the AUC was in L, being a weighted average of the acceptable FEV1 measurements recorded over 12 hours post dose