AEs in healthy male and female volunteers | ||||||
Single ascending dose (n=72) | ||||||
AE | 10 mg (n=10) | 20 mg (n=20) | 40 mg (n=10) | 80 mg (n=10) | 160 mg (n=10) | Placebo (n=12) |
All AEs, moderate | 0 (0) | 2 (10.0) | 0 (0) | 0 (0) | 4 (40.0) | 1 (8.3) |
All AEs, severe | 0 (0) | 1 (5.0) | 0 (0) | 0 (0) | 0 (0) | 1 (8.3) |
Gastrointestinal symptoms | ||||||
Nausea | 0 (0) | 2 (10.0) | 0 (0) | 0 (0) | 4 (40.0) | 0 (0) |
Vomiting | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 3 (30.0) | 0 (0) |
Nervous system symptoms | ||||||
Dizziness | 0 (0) | 3 (15.0) | 1 (10.0) | 3 (30.0) | 4 (40.0) | 2 (16.7) |
Fainting | 0 (0) | 1 (5.0) | 0 (0) | 0 (0) | 0 (0) | 1 (8.3) |
General symptoms | ||||||
Feeling hot | 0 (0) | 2 (10.0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Heart rate increased | 2 (20.0) | 1 (5.0) | 0 (0) | 0 (0) | 0 (0) | 2 (16.7) |
Orthostatic hypotension | 0 (0) | 1 (5.0) | 0 (0) | 0 (0) | 0 (0) | 1 (8.3) |
AEs in healthy male and female volunteers | ||||
Multiple ascending dose (n=48) | ||||
AE | 4×20 mg (n=12) | 4×40 mg (n=12) | 4×60 mg (n=12) | Placebo (n=12) |
All AEs, moderate | 2 (16.7) | 0 (0) | 1 (8.3) | 2 (16.7) |
All AEs, severe | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Gastrointestinal symptoms | ||||
Nausea | 1 (8.3) | 0 (0) | 2 (16.7) | 1 (8.3) |
Vomiting | 0 (0) | 0 (0) | 2 (16.7) | 0 (0) |
Nervous system symptoms | ||||
Dizziness | 2 (16.7) | 2 (16.7) | 3 (25.0) | 1 (8.3) |
General symptoms | ||||
Abdominal pain | 1 (8.3) | 0 (0) | 0 (0) | 0 (0) |
Headache | 2 (16.7) | 3 (25.0) | 1 (8.3) | 2 (16.7) |
Other | 5 (41.2) | 1 (8.3) | 1 (8.3) | 6 (50.0) |
AEs in MCI patients | |
Multiple dose (n=5) | |
Adverse event | 4×60 mg (n=5) |
All AEs, moderate | 0 (0) 1* |
All AEs, severe | 0 (0) |
Gastrointestinal symptoms | |
Nausea | 1 (20) 1* |
Vomiting | 0 (0) 1* |
Nervous system symptoms | |
Dizziness | 1 (20.0) |
General disorders | |
General pain | 1 (20.0) |
Headache | 5 (100.0) |
Other | 5 (100.0) |
The AEs, dizziness/fainting and orthostatic hypotension, were the most frequently observed safety observations during the course of this study. Orthostatic hypotension was observed in Posiphen treated people, but occurred with comparable frequency in placebo subjects. Some subjects experienced orthostatic effects at multiple measurement points postdose, but there was no apparent correlation between time of occurrence and plasma concentration of Posiphen. Dizziness, nausea and vomiting increased with Posiphen doses and at 160 mg there was a statistically significant effect of Posiphen on these two measures. In the multiple ascending dose studies there was a trend, but no statistically significant effect, in the 4×60 mg/day group.
↵* One person had leg cramps and was nauseous during the catheterisation (predrug). This subject vomited and dropped out after the second and before the third 60 mg dose on day 1.
MCI, mild cognitive impairment.