Safety Variables

Blood and urine samples for routine laboratory monitoring were taken at the time of admission into the study and on completion of the trial. At each clinic visit, the clinician recorded any unusual symptoms or adverse events.


Comparisons were made on changes from baseline to reduce the between-patient variability. Two-tailed tests were used throughout at the 95 percent level of significance (p<0.05). Students t test was used in the analysis of pulmonary function and laboratory data (Mann-Whitney U test for differential white cell counts) and the Mann-Whitney U test was used in the analysis of all other variables. The most important efficacy variables were considered to be the patient-generated data, patient and clinician assessment of treatment efficacy, and the ability of patients to tolerate reduction and withdrawal of theophylline therapy. Safety was assessed primarily from reports of unusual symptoms or adverse reactions and comparison of laboratory variables at entry and at the end of the study.No patients were withdrawn from the study. Compliance with the protocol was excellent. All patients kept their dose of theophylline constant during the baseline and the first four weeks of treatment. Reduction in theophylline use occurred as per protocol during weeks 5 to 6, and no patient received theophylline during weeks 7 to 8. All patients were included in the analysis of efficacy and safety. comments

Efficacy—Diary Card

Symptom Scores: Symptom severity was greater in the nedocromil sodium group compared with the placebo group during the baseline, significantly so (p<0.05) for nighttime asthma. When test treatment was added to the existing bronchodilator therapy (weeks 1 to 4), there was a marked reduction (^30 percent) in all symptom severity scores for the nedocromil sodium group but no change from baseline for the placebo group (Fig 1). When theophylline dosage was reduced (weeks 5 to 6), symptom scores increased in the placebo group (nighttime asthma score doubled and morning tightness and cough severity scores increased by 50 percent) but remained lower than baseline in the nedocromil sodium group. When theophylline therapy was withdrawn (weeks 7 to 8), all four symptom scores returned to baseline in the nedocromil sodium group but increased to approximately double the baseline levels in the placebo group. Treatment group differences were highly significant (p<0.001) for day and nighttime asthma and increased in significance for morning tightness (p<0.05 to p<0.001) throughout the treatment phase. Treatment group differences were significant for cough severity during weeks 3 to 4 (p<0.05) and weeks 5 to 6 and 7 to 8 (p<0.01).


Baseline Values
NighttimeAsthma MorningTightness DaytimeAsthma Cough
Nedocromilsodium ■I 1.05 ± 1.52 ± 1.45 ± 0.93 ±
0.20 0.19 0.16 0.20
Placebo 0.55 ± 1.09± 1.18 ± 0.59 ±
0.10 0.06 0.07 0.11

Downward black and white arrow = theophylline reduction; downward open arrow = theophylline withdrawal; three asterisks = p<0.001; two asterisks = p<0.01; one asterisk = p<0.05. Error bars are standard error of the mean.

Figure 1. Change from baseline in diary card symptom severity scores. Severity score scale: 0 = none to 4 = severe.







Category: asthma / Tags: Bronchodilator therapy, Chronic Asthma, Nedocromil Sodium