DISCUSSION
Mesdopetam (formerly IRL790) is a novel compound for the treatment of
dyskinesia and psychosis in PD. This was a FIH study investigating the
safety, tolerability, and pharmacokinetics after single and repeated
oral administrations of mesdopetam.
During the initial single dose escalation five escalating doses of
IRL790 were tested in 16 male subjects included in two alternating
cohorts with eight subjects in each. At each dose level two subjects
were given placebo and six subjects were given IRL790, using a partial
cross-over design.
The multiple dose escalation included 23 healthy male subjects. IRL790
was administered as once daily doses for 10 consecutive days in doses 40
mg and 80 mg.
Overall, IRL790 was well tolerated up to 120 mg single dose and up to 80
mg multiple dose although an increased frequency of AEs withinNervous system disorders assessed as probably related to study
treatment was seen after multiple dosing at the higher dose level (80
mg), as compared to 40 mg. No SAEs occurred and no AEs led to
withdrawal.
The AEs that occurred in one subject administered a single dose of 160
mg were assessed as being probably related to the study drug as
antidopaminergic symptoms, and the dose was reduced to 120 mg for the
remaining subjects. These AEs were uncomfortable for the subject, but
short-lasting and not serious.
There were no remarkable mean changes over time or individual clinically
significant abnormal findings in vital signs, physical examination or
ECG parameters at any of the time-points assessed in the SAD or the MAD
part of the study. Safety laboratory parameters did not show any
significant abnormal changes. A modest, dose dependent increase in
s-prolactin was observed after both on the SAD and MAD parts of the
study, consistent with target engagement at pituitary dopamine
receptors.