In the present trial, as expected, patients who were randomized to A5 monotherapy continued to have a benefit on BP control during the 8 weeks’ randomized treatment period, even though they did not respond adequately to the 6-week open-label treatment. In non-responder trials, further BP reduction during the double-blind treatment phase in those patients who continue to receive the same monotherapy as in the run-in phase is a common observation. This is due not only to the placebo effect but also to the regression-to-the-mean phenomenon. The crucial factor in such trials is to demonstrate a statistically significant and clinically relevant additional BP reduction in response to the combination therapy in patients who did not respond adequately to standard therapeutic doses of the monotherapy.