From the results of these 2 studies, it is concluded that:

• The Holter Bin method, which allows comparison of direct QT interval measurements,
is reproducible, sensitive, capable of demonstrating a statistically significant change in
QT interval as small as 2 to 3 msec, and is appropriate to assess drugs that modify HR.

• The =2.9 msec mean increase in QT interval recorded with alfuzosin at 4 times the
therapeutic dose is less than that observed with moxifloxacin at its therapeutic dose.
This small increase in QT interval is below the range suspected to be associated with
torsades de pointes [preliminary concept paper (5)].

These conclusions are corroborated by the large clinical experience on the safety profile
of alfuzosin in patients with BPH, a population of male patients, generally older than
65 years-of-age and suffering in more than 40% of cases from associated cardiovascular
diseases. Specifically:

• No signal regarding cardiac arrhythmia related to QT/QTc interval prolongation with
alfuzosin was detected in the clinical trials safety database (more than 2000 patients
treated with alfuzosin in phase II/III controlled trials).

• A strong confirmation of this statement is provided by the large post-marketing
experience with alfuzosin (more than 130,000 patients in cohort observational surveys
and a number of days of therapy superior to 1350 millions). No arrhythmogenic signal
is detected in a population unrestricted for prescription.

In conclusion:

• The Holter Bin method is confirmed as a valuable method to assess the effect on QT
interval of a drug that affects HR.

• Thorough clinical assessment of the effect of alfuzosin on QT interval is not indicative
of a prolongation of QT interval that could be associated with ventricular arrhythmia.
This conclusion is corroborated by the absence of a signal of ventricular arrhythmia in
a large clinical and post-marketing experience.