Subjects could not use inhaled or oral steroids, cromolyn sodium, or long-acting theophylline for the treatment of asthma. Acetaminophen was the sole nonprescription medication permitted for analgesia. Subjects were not permitted to receive prescription medications for acute exacerbation of asthma within 12 h of each trial period. Prescription medication was permitted during the study only after mutual consent of the investigator and the sponsor. All subjects were prohibited from consuming alcohol, caffeine, or any medication (other than those permitted above) that could theoretically interact with the trial medication. Written informed consent was obtained from each subject, and the study was approved by the appropriate Institutional Review Board (Western Institutional Review Board, Olympia, Wash).
During the 2 weeks before the trial, each subject provided a medical history and underwent a complete physical examination, 12-lead electrocardiography, routine clinical laboratory tests, a urine screen for drug abuse, pulmonary function tests, measurements of vital signs, and a determination of subjective symptoms. Subjects stopped taking all asthma and allergy medications at least 12 h before entering the study. canadian neightbor pharmacy
The study consisted of three successive treatment periods separated by 3-day to 4-week intervals. Total treatment was completed within 3 months and took place when there was no evidence of ragweed in the environment. Three formulations of ICI 204,219 were used in this trial. Each formulation was a suspension of ICI 204,219 in chlorofluorocarbons combined with a surfactant, which served as a suspending agent and aided in lubricating the valve. Formulation 1 contained an amorphous bulk drug that is used in oral formulations, whereas formulations 2 and 3 contained a crystalline bulk drug. The delivery and dispersal characteristics were not significantly different among the three formulations. A single 0.2-mg dose of each formulation of ICI 204,219 was administered during treatment periods by means of a metered-dose inhaler: formulation 1, delivered in four actuations at 0.05 mg of drug per actuation; formulation 2, delivered in four actuations at 0.05 mg of drug per actuation; and formulation 3, delivered in one actuation at 0.2 mg of drug per actuation.
Bronchoprovocation was performed with a standardized ragweed allergen, provided the subject had an FEV, of at least 65 percent of the predicted normal value and within ± 15 percent of the screening FEV, value. Allergen was delivered by means of a nebulizer (DeVilbiss No. 646, DeVilbiss Company, Somerset, Pa) during slow, submaximal inspiration from functional residual capacity to near total lung capacity. The nebulizer was attached to a dose-monitoring device (Rosenthal-French Dosimeter, Laboratory for Applied Immunology, Inc, Fairfax, Va), consisting of a breath-actuated solenoid valve timing circuit and compressed air supply at 20 pounds per square inch (PSI). The solenoid valve was set to remain in the open position for 0.6 s at the onset of inspiration. After the solenoid valve closed, inspiration continued for another 0.5 s. Each subject was instructed to hold his or her breath for 2 to 5 s after inhalation before exhaling.