Safety outcomes
In both studies all AEs were mild with the exception of upper limb
fracture (n=1 in PK study; considered unrelated to study medicine). No
serious AEs were reported, ECG findings revealed no QT prolongations or
conduction abnormalities, and there were no clinically significant
changes in haematology or blood chemistry parameters. Isolated,
out-of-range blood pressure values were noted in both studies but were
considered not clinically significant.
In the PK study, overall exposure to MR309 was the same for patients
receiving 400 QD and 200 BID dosing (10 days, each). Treatment-emergent
AEs (n=9, 56.3% vs n=6, 37.5%) and treatment-related AEs (n=7, 43.8 vs
n=3, 18.8%) were more frequent with MR309 400 mg QD versus 200 mg BID.
The only AEs reported in ≥10% of individuals were dizziness (400 mg QD:
n=3, 18.8%; 200 mg BID: n=1, 6.3%) and symptomatic orthostatic
tachycardia (400 mg QD: n=2, 12.5%; 200 mg BID: n=1, 6.3%). All cases
of symptomatic orthostatic tachycardia were transient and, while
considered related to study medication, a direct causal relation was
unclear as in two of three individuals the event was reported pre-dose
when plasma levels of MR309 were unquantifiable. One case of
asymptomatic orthostatic tachycardia was also observed during screening
(pre-dose, Day 1) and considered unrelated to study medication.
In the PET study, 4 participants
(57.1%) reported 6 AEs: dizziness (3 instances in n=2; all considered
related to study medication), contusion and dysgeusia (2 instances in
n=2 and 1 instance in n=1, respectively; all AEs were considered
unrelated to study medication).