To avoid burdening the volunteer patients unnecessarily, and being convinced that the administration of higher doses of the trial drugs would not give any further useful information, we decided in the protocol that the study could be ended prematurely on any of the study days—without running into problems of tolerability (such as feeling unwell, T-wave flattening, or rises in pulse rate above 140-min” *)—whenever an individual patient reached a maximal FEV, value. This was considered to be the case when the FEV, value had increased to more than 110 percent of the predicted value, or when it failed to increase by 5 percent or more after the last two drug doses. This latter was the case in 11 of the 12 patients who ended the study somewhat prematurely.
Only one patient (No. 5) went right through the planned dosage scheme. This patient was known to us to have severe nocturnal asthma. He had failed to react in a standard way to salbutamol 200 fig inhalations in a previous study, even when the drug had been given to him at 4 am and 8 am. However, he had no problems with the high doses that were given to him in the present study (228 |xg of formoterol and 3,800 |xg of salbutamol), and he actually felt subjectively better on these days with “freedom in the chest as never before.”