Asthma Respiratory Asthma
Conditions
Interventions
Subjects were randomly assigned to one of the four treatment groups in blocks of four patients according to a computer-generated randomization schedule prepared by the sponsor. Participants receive 3
Sponsors
Roberts Pharmaceutical Corporation
ABC farmaceutici
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and nonpregnant females. Women of childbearing potential had to use acceptable methods of birth control and have a negative prestudy serum ß-hCG pregnancy test. Acceptable methods of birth control were limited to vaginal or intrauterine contraceptive devices or agents and natural (postmenopausal) or surgical sterility. Abstention, oral contraceptives, and use of contraceptive by the woman’s partner were not acceptable methods of birth control 2. Age: adults, 16 years of age or older 3. Health status: nonsmokers for at least 6 months before entering the study, in good physical condition with a more than 1-year history of chronic, extrinsic reversible hyperreactive airway disease (asthma) 4. Willing to undergo the procedures required in the protocol 5. Willing to undergo a chest x-ray if required by the Principal Investigator 6. On screening, subjects must have had a baseline FEV1 value within 50% to 80% of the predicted FEV1 value for their age and height, when immediate-release theophylline or sustained-release theophylline had been withheld for at least 24 hours. Subjects were further required to have abstained from use of any sympathomimetic, including beta-agonist inhalers, for at least 8 hours before the screening pulmonary function tests (PFTs) 7. On screening, subjects had to show at least a 15% increase in FEV1 30 minutes after administration of a standard dose (2 puffs, 180 µg) of albuterol 8. Subjects must have demonstrated, by verbal history, a period of at least 1 month of acceptable clinical control of their asthma in the preceding 3 years using oral theophylline, alone or in combination with a beta-agonist inhaler 9. Subjects had to weight at least 48 kg (105 lb)
Exclusion criteria
Exclusion criteria: 1. Clinically significant deviation from normal in physical examination, laboratory parameters, ECG, or chest x-ray, as evaluated by the Principal Investigator, that would have precluded the subject’s participation in the study 2. Clinically significant coexisting disease, including: 2.1. Clinically significant cardiovascular disease, including a history of congestive heart failure 2.2. Angina pectoris within 1 year 2.3. History of myocardial infarction within 1 year 2.4. Convulsive disorder 2.5. Clinically significant gastrointestinal disease, including active peptic ulcers within the preceding 5 years 2.6. Renal disease 2.7. Hepatic disease 2.8. Hematologic disease 2.9. Insulin-dependent diabetes mellitus 2.10. Nonreversible chronic pulmonary disease 2.11. Known infection with human immunodeficiency virus 2.12. Chronic obstructive pulmonary disease 3. Presence of any acute illness 4. Sensitivity to theophylline or theophylline-like agents 5. A resting heart rate of less than 50 bpm or greater than 100 bpm and/or an arterial blood pressure of less than 100/60 mmHg or greater than 140/90 mmHg when sitting 6. History of alcohol, narcotic, barbiturate, marijuana, or polydrug abuse 7. Participation in other investigational drug studies within 30 days before the start of this study 8. Subjects who were unlikely to be compliant with the protocol requirements 9. Oral contraceptive use was not allowed because of the propensity for these drugs to decrease theophylline clearance. If a woman became pregnant during the study, she was to be withdrawn from the study 10. Nursing mothers 11. Subjects using aerosol steroids were required to discontinue their use at least 1 month before the study and to refrain from using them throughout the entire study. Subjects using oral steroids to control bronchoconstriction were excluded from participation. Subjects using cromolyn sodium or oral steroids were required to discontinue their use at least 1 month before the study and to refrain from using them throughout the entire study, with the exception of acute steroid burst treatment 12. Due to their effects on theophylline clearance, none of the following could be taken during the study: allopurinol, ciprofloxacin, erythromycin, troleandomycin, lithium carbonate, phenytoin, rifampin, or cimetidine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcome was the forced expiratory volume in 1 s (FEV1). The derived variable that was considered for comparative assessments among treatments was the percent change in the 2 hours FEV1 value from the baseline value (T0, hour 0). The primary timepoint was the last observation that was reported for each subject during the double-blind treatment period (3 months). FEV1 values were measured by using pulmonary function tests (PFTs) at day 1 (T0) and after at week 2, week 4, week 6, week 8, week 10, week 12. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The secondary outcome variables were forced vital capacity (FVC), FEV1/FVC, forced expiratory flow during the middle half of the FVC (FEF25%-75%) and peak expiratory flow rate (PEFR). These outcomes were expressed as the percent change in the 2 hours values from the baseline value (T0, hour 0). The endpoint was the last observation that was reported for each subject during the double-blind treatment period (3 months). These secondary outcomes were measured by using PFTs at day 1 (T0) and after at week 2, week 4, week 6, week 8, week 10, week 12. 2. Secondary efficacy variables derived from the Medication/Symptom Diaries were asthmatic attack rate (total number of attacks divided by the total number of days on study medication), albuterol use rate (total number of puffs divided by total number of days on study medication), average daily peak flow meter (PFM) rate, and global assessment. For the daily PFM rate, the percent change from baseline (T0) was calculated. For the remaining efficacy variables derived from the Medication/Symptom Diaries, the absolute change from baseline (T0) was determined. “Baseline” for these variables was defined as the value obtained from the diaries during the placebo run-in phase, after that these secondary outcomes were measured at week 2, week 4, week 6, week 8, week 10, week 12. 3. Safety was assessed by physical examinations, ECGs, and the recording of vital signs, laboratory test results, and adverse events. All clinical adverse events (AE) entered on the Case Report Forms (CRFs) were to be classified as to possible relation to study medication (not related, possibly related, definitely related, or unknown) and severity (mild, moderate, or severe). Also recorded for each AE were the start and stop dates, the action taken (none, study medication discontinued, or treatment prescribed), and the outcome (recovered, recovered with sequelae, under treatment, deceased, unknown, or ongoing). If a subject experienced an AE leading to with | — |
Countries
United States of America
Outcome results
None listed