| Population | Placebo N = 861 |
Xanomeline Low Dose N = 841 |
Xanomeline High Dose N = 841 |
Overall N = 2541 |
|---|---|---|---|---|
| Randomised | 86 (100%) | 84 (100%) | 84 (100%) | 254 (100%) |
| Intention-to-treat population | 86 (100%) | 84 (100%) | 84 (100%) | 254 (100%) |
| Safety population | 86 (100%) | 84 (100%) | 84 (100%) | 254 (100%) |
| Per-protocol population | 58 (67%) | 25 (30%) | 27 (32%) | 110 (43%) |
| 1 n (%) | ||||
| Percentages use the number of randomised subjects in each treatment group as denominator. Every randomised subject received at least one dose of study drug, so the randomised, intention-to-treat and safety populations contain the same subjects; they are counted here under planned treatment, whereas safety outputs count them under actual treatment. | ||||
5 Study patients
5.1 Analysis populations
Every randomised subject received at least one dose of study drug, so the randomised, intention-to-treat and safety populations contain the same subjects. They are not interchangeable in the tables that follow: population tables and efficacy analyses count subjects under the treatment to which they were randomised, whereas safety analyses count them under the treatment actually received, and 12 subjects randomised to the high dose received the low dose instead.
5.2 Disposition of subjects
| Disposition | Placebo N = 861 |
Xanomeline Low Dose N = 841 |
Xanomeline High Dose N = 841 |
Overall N = 2541 |
|---|---|---|---|---|
| Randomised | 86 (100%) | 84 (100%) | 84 (100%) | 254 (100%) |
| Treated (safety population) | 86 (100%) | 84 (100%) | 84 (100%) | 254 (100%) |
| Completed the study | 58 (67%) | 25 (30%) | 27 (32%) | 110 (43%) |
| Discontinued the study | 28 (33%) | 59 (70%) | 57 (68%) | 144 (57%) |
| Reason for discontinuation | ||||
| Adverse event | 8 (29%) | 44 (75%) | 40 (70%) | 92 (64%) |
| Withdrawal by subject | 9 (32%) | 10 (17%) | 8 (14%) | 27 (19%) |
| Study terminated by sponsor | 2 (7.1%) | 2 (3.4%) | 3 (5.3%) | 7 (4.9%) |
| Protocol violation | 2 (7.1%) | 1 (1.7%) | 3 (5.3%) | 6 (4.2%) |
| Lack of efficacy | 3 (11%) | 0 (0%) | 1 (1.8%) | 4 (2.8%) |
| Death | 2 (7.1%) | 1 (1.7%) | 0 (0%) | 3 (2.1%) |
| Physician decision | 1 (3.6%) | 0 (0%) | 2 (3.5%) | 3 (2.1%) |
| Lost to follow-up | 1 (3.6%) | 1 (1.7%) | 0 (0%) | 2 (1.4%) |
| Died | 2 (2.3%) | 1 (1.2%) | 0 (0%) | 3 (1.2%) |
| 1 n (%) | ||||
| Percentages use the number of randomised subjects in each treatment group as denominator, except for the reasons for discontinuation, which use the number of subjects who discontinued in that group and therefore sum to 100%. Reasons come from the disposition domain; the pilot ADSL does not carry them. | ||||
144 subjects discontinued the study before the end of the treatment period, and 3 deaths were reported. The most frequent reason for discontinuation was adverse event, recorded for 92 of the 144 subjects who discontinued, and discontinuation was more frequent in the xanomeline groups than in the placebo group.
5.3 Protocol deviations
The pilot study underlying this demonstration ships no protocol deviation dataset, so deviations can be reported only where they ended a subject’s participation. 6 subjects discontinued for a protocol violation; they are listed in Listing 16.2.2.1. Deviations that did not lead to discontinuation cannot be counted here, so no statement is made about their number or their effect on the primary endpoint.