Table 2.
Adverse events and safety during 5 weeks of treatment with xanomeline–trospium demonstrate that incidence of cholinergic/anticholinergic adverse events was higher with active treatment versus placebo, but the percentage of patients who discontinued treatment were similar across both groups (safety population) [128]
| Variable | Xanomeline–trospium (N = 89) | Placebo (N = 90) |
|---|---|---|
| Any AE | 48 (54) | 39 (43) |
| SAEa | 1 (1) | 0 (0) |
| Severe AEb | 1 (1) | 1 (1) |
| AE leading to discontinuation | 2 (2) | 2 (2) |
| AE occurring in ≥ 2% of patients in xanomeline–trospium group | ||
| Constipation | 15 (17) | 3 (3) |
| Nausea | 15 (17) | 4 (4) |
| Dry mouth | 8 (9) | 1 (1) |
| Dyspepsia | 8 (9) | 4 (4) |
| Vomiting | 8 (9) | 4 (4) |
| Headache | 6 (7) | 5 (6) |
| Somnolence | 5 (6) | 4 (4) |
| Akathisia | 3 (3) | 0 (0) |
| Dizziness | 3 (3) | 3 (3) |
| Increased weight | 3 (3) | 4 (4) |
| Tachycardia | 3 (3) | 2 (2) |
| Sedation | 2 (2) | 2 (2) |
| Diarrhea | 2 (2) | 4 (4) |
| Increased γ-glutamyltransferase level | 2 (2) | 0 (0) |
| Agitation | 2 (2) | 1 (1) |
| Insomnia | 2 (2) | 2 (2) |
| Decreased appetite | 2 (2) | 0 (0) |
| Hyperhidrosis | 2 (2) | 1 (1) |
| Mean change from baseline to week 5 in body weight, kg | 1.5 ± 2.8 | 1.1 ± 3.5 |
| Mean change from baseline to week 5 in score Simpson–Angus Scalec | − 0.1 ± 0.7 | − 0.1 ± 0.8 |
| Mean change from baseline to week 5 in Barnes Akathisia Rating Scaled | − 0.1 ± 1.0 | 0.0 ± 0.7 |
Data are given as n (%) or mean ± SD. The safety population included all the patients who had undergone randomization and had received at least one dose of xanomeline–trospium or placebo. Adverse events that occurred during the treatment period were defined as those that started or worsened from the time of the first dose of xanomeline–trospium or placebo (visit 1 at day 2) to the time of discharge (visit 9 at day 35). From New England Journal of Medicine, Brannan et al. [128]. Copyright © 2021 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
AE adverse event, SAE serious adverse event
aA serious adverse event was defined as any adverse event that resulted in death, was immediately life threatening, led to inpatient hospitalization or prolongation of hospitalization, or caused persistent or clinically significant disability or incapacity
bA severe adverse event was defined as any event that was incapacitating or caused an inability to perform normal activities of daily living
cScores on the Simpson–Angus Scale range from 0 to 40; higher scores indicate greater severity of drug-induced parkinsonian symptoms
dScores on the Barnes Akathisia Rating Scale range from 0 to 14; higher scores indicate greater symptoms of akathisia