Primary objective: To investigate the safety and local tolerability of increasing cumulative doses (2, 4, 6 actuations) of a low (0.1%) and a high (0.5%) concentration of BHT administered via oral inhalation with the Respimat® inhaler B (RMT-B) vs. 2 inhalation solutions without BHT (placebo to BHT given by RMT B and placebo given by hydroxylfluoralkane metered dose inhaler (HFA MDI)). In a first step, the trial was performed in healthy subjects and - if no safety concerns arose - in a second step in patients with mild asthma who were sensitive to metacholine in a respective challenge test. Secondary objective: To explore the pharmacokinetics (PK) of BHT.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
61
Maximum decrease of forced expiratory volume in one second (FEV1)
(Minimum FEV1 value over the interval 5 min to 2 h 50 min) minus (baseline value)
Time frame: baseline, 3 h after administration
Maximum decrease in FEV1 after 2 actuations
(minimum FEV1 value over the interval 5 min to 50 min) - (baseline value)
Time frame: baseline, up to 50 minutes after drug administration
Maximum decrease in FEV1 after 4 actuations
(minimum FEV1 value over the interval 1 h 5 min to 1 h 50 min) - (baseline value)
Time frame: baseline, up to 1:50 hours after drug administration
Maximum decrease in FEV1 after 6 actuations
(minimum FEV1 value over the interval 2 h 5 min to 2 h 50 min) - (baseline value)
Time frame: baseline, up to 2:50 hours after drug administration
Number of subjects with a decrease in FEV1
stratified into classes of 0-20%, \>20-40%, and \>40%
Time frame: baseline, up to 2:50 hours after drug administration
Number of patients with cough episodes
within 5 min prior to the 1st inhalation and within 5 min after each of the 3 inhalations on each treatment day
Time frame: up to 9 days
Number of patients requiring rescue medication
Time frame: up to 60 min after each dosing
Number of patients with adverse events
Time frame: up to 10 days after the last treatment day
Cmax (maximum measured concentration of the analyte in plasma)
Time frame: pre-dose, 2, 10, 25 and 55 min after each dosing
tmax (time from dosing to maximum measured concentration of the analyte in plasma)
Time frame: pre-dose, 2, 10, 25 and 55 min after each dosing
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable concentration at tz)
Time frame: pre-dose, 2, 10, 25 and 55 min after each dosing
Area under the curve (AUC) of FEV1
Time frame: over 3 hours after first dosing
AUC of FEV1
Time frame: over 1 hours after each dosing
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