| Subject | Treatment | Age (years) | Sex | Treatment duration (days) | Reason for discontinuation |
|---|---|---|---|---|---|
| 01-701-1023 | Placebo | 64 | Male | 28 | Adverse event |
| 01-701-1047 | Placebo | 85 | Female | 26 | Adverse event |
| 01-701-1345 | Placebo | 63 | Female | 162 | Study terminated by sponsor |
| 01-701-1387 | Placebo | 87 | Female | 14 | Protocol violation |
| 01-703-1096 | Placebo | 81 | Female | 51 | Lost to follow-up |
| 01-703-1175 | Placebo | 75 | Male | 7 | Protocol violation |
| 01-704-1010 | Placebo | 80 | Male | 138 | Withdrawal by subject |
| 01-704-1233 | Placebo | 87 | Female | 15 | Withdrawal by subject |
| 01-704-1260 | Placebo | 71 | Female | 67 | Withdrawal by subject |
| 01-704-1435 | Placebo | 74 | Male | 54 | Withdrawal by subject |
| 01-704-1445 | Placebo | 75 | Male | 175 | Death |
| 01-705-1018 | Placebo | 69 | Female | NA | Withdrawal by subject |
| 01-705-1059 | Placebo | 66 | Female | 123 | Adverse event |
| 01-705-1186 | Placebo | 84 | Female | 19 | Physician decision |
| 01-708-1158 | Placebo | 81 | Female | 42 | Adverse event |
| 01-708-1378 | Placebo | 67 | Male | 148 | Study terminated by sponsor |
| 01-709-1259 | Placebo | 82 | Male | 139 | Lack of efficacy |
| 01-709-1306 | Placebo | 60 | Female | 134 | Adverse event |
| 01-710-1083 | Placebo | 89 | Female | 11 | Death |
| 01-710-1264 | Placebo | 78 | Male | 121 | Adverse event |
| 01-710-1271 | Placebo | 86 | Female | 56 | Adverse event |
| 01-710-1314 | Placebo | 78 | Female | 30 | Withdrawal by subject |
| 01-710-1315 | Placebo | 83 | Female | 130 | Adverse event |
| 01-715-1155 | Placebo | 59 | Female | 44 | Withdrawal by subject |
| 01-716-1308 | Placebo | 76 | Female | 41 | Withdrawal by subject |
| 01-717-1201 | Placebo | 85 | Female | 65 | Lack of efficacy |
| 01-717-1344 | Placebo | 64 | Female | 63 | Lack of efficacy |
| 01-718-1172 | Placebo | 74 | Male | 70 | Withdrawal by subject |
| 01-701-1033 | Xanomeline Low Dose | 74 | Male | 14 | Study terminated by sponsor |
| 01-701-1111 | Xanomeline Low Dose | 81 | Female | 10 | Adverse event |
| 01-701-1115 | Xanomeline Low Dose | 84 | Male | 55 | Adverse event |
| 01-701-1188 | Xanomeline Low Dose | 71 | Male | 38 | Adverse event |
| 01-701-1211 | Xanomeline Low Dose | 76 | Female | 59 | Death |
| 01-701-1294 | Xanomeline Low Dose | 67 | Male | 83 | Adverse event |
| 01-701-1341 | Xanomeline Low Dose | 51 | Male | 22 | Adverse event |
| 01-701-1429 | Xanomeline Low Dose | 84 | Female | 43 | Withdrawal by subject |
| 01-702-1082 | Xanomeline Low Dose | 84 | Female | 80 | Withdrawal by subject |
| 01-703-1086 | Xanomeline Low Dose | 71 | Male | 94 | Adverse event |
| 01-703-1119 | Xanomeline Low Dose | 81 | Female | 114 | Adverse event |
| 01-703-1182 | Xanomeline Low Dose | 84 | Male | 56 | Adverse event |
| 01-703-1197 | Xanomeline Low Dose | 76 | Female | 14 | Withdrawal by subject |
| 01-703-1279 | Xanomeline Low Dose | 72 | Female | 22 | Withdrawal by subject |
| 01-704-1009 | Xanomeline Low Dose | 83 | Male | 30 | Withdrawal by subject |
| 01-704-1025 | Xanomeline Low Dose | 81 | Female | 28 | Adverse event |
| 01-704-1114 | Xanomeline Low Dose | 77 | Male | 166 | Withdrawal by subject |
| 01-704-1120 | Xanomeline Low Dose | 71 | Female | 62 | Adverse event |
| 01-704-1323 | Xanomeline Low Dose | 68 | Female | 29 | Adverse event |
| 01-704-1325 | Xanomeline Low Dose | 81 | Male | 73 | Protocol violation |
| 01-705-1031 | Xanomeline Low Dose | 56 | Female | 22 | Lost to follow-up |
| 01-705-1199 | Xanomeline Low Dose | 87 | Male | 13 | Adverse event |
| 01-705-1393 | Xanomeline Low Dose | 84 | Female | 148 | Adverse event |
| 01-706-1384 | Xanomeline Low Dose | 74 | Female | 10 | Adverse event |
| 01-707-1037 | Xanomeline Low Dose | 72 | Female | 5 | Withdrawal by subject |
| 01-708-1019 | Xanomeline Low Dose | 68 | Male | 13 | Adverse event |
| 01-708-1032 | Xanomeline Low Dose | 62 | Male | 21 | Adverse event |
| 01-708-1272 | Xanomeline Low Dose | 82 | Male | 45 | Withdrawal by subject |
| 01-708-1297 | Xanomeline Low Dose | 61 | Male | 99 | Adverse event |
| 01-708-1353 | Xanomeline Low Dose | 87 | Female | 56 | Adverse event |
| 01-708-1428 | Xanomeline Low Dose | 84 | Female | 36 | Adverse event |
| 01-709-1007 | Xanomeline Low Dose | 54 | Female | 29 | Adverse event |
| 01-709-1081 | Xanomeline Low Dose | 86 | Female | 100 | Adverse event |
| 01-709-1102 | Xanomeline Low Dose | 71 | Female | 72 | Adverse event |
| 01-709-1217 | Xanomeline Low Dose | 77 | Male | 100 | Adverse event |
| 01-709-1285 | Xanomeline Low Dose | 87 | Male | 61 | Study terminated by sponsor |
| 01-710-1002 | Xanomeline Low Dose | 88 | Male | 5 | Adverse event |
| 01-710-1045 | Xanomeline Low Dose | 83 | Female | 72 | Adverse event |
| 01-710-1053 | Xanomeline Low Dose | 84 | Female | 47 | Adverse event |
| 01-710-1154 | Xanomeline Low Dose | 84 | Male | 30 | Adverse event |
| 01-710-1166 | Xanomeline Low Dose | 81 | Female | 110 | Adverse event |
| 01-710-1270 | Xanomeline Low Dose | 83 | Female | 18 | Adverse event |
| 01-710-1300 | Xanomeline Low Dose | 78 | Female | 63 | Adverse event |
| 01-710-1358 | Xanomeline Low Dose | 82 | Male | 146 | Withdrawal by subject |
| 01-710-1385 | Xanomeline Low Dose | 77 | Male | 113 | Adverse event |
| 01-711-1143 | Xanomeline Low Dose | 76 | Female | 58 | Adverse event |
| 01-713-1448 | Xanomeline Low Dose | 71 | Female | 118 | Adverse event |
| 01-714-1068 | Xanomeline Low Dose | 79 | Female | 62 | Adverse event |
| 01-715-1107 | Xanomeline Low Dose | 65 | Male | 71 | Adverse event |
| 01-715-1405 | Xanomeline Low Dose | 69 | Male | 2 | Adverse event |
| 01-716-1063 | Xanomeline Low Dose | 80 | Male | 109 | Adverse event |
| 01-716-1094 | Xanomeline Low Dose | 82 | Male | 37 | Adverse event |
| 01-716-1151 | Xanomeline Low Dose | 83 | Female | 100 | Adverse event |
| 01-716-1298 | Xanomeline Low Dose | 76 | Female | 82 | Adverse event |
| 01-716-1311 | Xanomeline Low Dose | 78 | Male | 131 | Withdrawal by subject |
| 01-718-1066 | Xanomeline Low Dose | 79 | Female | 10 | Adverse event |
| 01-718-1079 | Xanomeline Low Dose | 67 | Female | 43 | Adverse event |
| 01-718-1170 | Xanomeline Low Dose | 80 | Female | 27 | Adverse event |
| 01-718-1250 | Xanomeline Low Dose | 82 | Female | 133 | Adverse event |
| 01-701-1146 | Xanomeline High Dose | 75 | Female | 38 | Adverse event |
| 01-701-1180 | Xanomeline High Dose | 56 | Male | 35 | Adverse event |
| 01-701-1181 | Xanomeline High Dose | 79 | Female | 5 | Adverse event |
| 01-701-1275 | Xanomeline High Dose | 61 | Male | 114 | Withdrawal by subject |
| 01-701-1302 | Xanomeline High Dose | 61 | Male | 69 | Adverse event |
| 01-701-1360 | Xanomeline High Dose | 67 | Male | 6 | Physician decision |
| 01-701-1444 | Xanomeline High Dose | 63 | Male | 39 | Adverse event |
| 01-703-1076 | Xanomeline High Dose | 69 | Male | 61 | Adverse event |
| 01-703-1258 | Xanomeline High Dose | 78 | Female | 176 | Adverse event |
| 01-703-1295 | Xanomeline High Dose | 88 | Female | 150 | Withdrawal by subject |
| 01-703-1335 | Xanomeline High Dose | 67 | Female | 52 | Protocol violation |
| 01-703-1403 | Xanomeline High Dose | 67 | Male | 2 | Adverse event |
| 01-704-1008 | Xanomeline High Dose | 76 | Female | 40 | Adverse event |
| 01-704-1017 | Xanomeline High Dose | 77 | Male | 44 | Adverse event |
| 01-704-1065 | Xanomeline High Dose | 75 | Male | 60 | Adverse event |
| 01-704-1074 | Xanomeline High Dose | 80 | Female | 58 | Adverse event |
| 01-704-1093 | Xanomeline High Dose | 79 | Male | 95 | Adverse event |
| 01-704-1241 | Xanomeline High Dose | 86 | Male | 46 | Adverse event |
| 01-704-1266 | Xanomeline High Dose | 82 | Male | 55 | Adverse event |
| 01-704-1332 | Xanomeline High Dose | 80 | Male | 68 | Adverse event |
| 01-705-1281 | Xanomeline High Dose | 73 | Female | 92 | Adverse event |
| 01-705-1303 | Xanomeline High Dose | 72 | Male | 15 | Adverse event |
| 01-705-1310 | Xanomeline High Dose | 74 | Female | 83 | Adverse event |
| 01-705-1377 | Xanomeline High Dose | 63 | Female | 22 | Withdrawal by subject |
| 01-705-1382 | Xanomeline High Dose | 82 | Male | NA | Protocol violation |
| 01-706-1049 | Xanomeline High Dose | 60 | Female | 36 | Adverse event |
| 01-708-1178 | Xanomeline High Dose | 77 | Female | 99 | Physician decision |
| 01-708-1213 | Xanomeline High Dose | 76 | Female | 14 | Adverse event |
| 01-708-1216 | Xanomeline High Dose | 78 | Male | 37 | Adverse event |
| 01-708-1236 | Xanomeline High Dose | 86 | Female | 1 | Withdrawal by subject |
| 01-708-1347 | Xanomeline High Dose | 61 | Female | 60 | Adverse event |
| 01-708-1372 | Xanomeline High Dose | 84 | Male | 8 | Protocol violation |
| 01-709-1168 | Xanomeline High Dose | 72 | Female | 56 | Adverse event |
| 01-709-1238 | Xanomeline High Dose | 69 | Male | 84 | Adverse event |
| 01-709-1329 | Xanomeline High Dose | 70 | Male | 11 | Withdrawal by subject |
| 01-709-1424 | Xanomeline High Dose | 77 | Male | 5 | Adverse event |
| 01-710-1021 | Xanomeline High Dose | 79 | Male | 33 | Adverse event |
| 01-710-1070 | Xanomeline High Dose | 85 | Female | 137 | Adverse event |
| 01-710-1137 | Xanomeline High Dose | 79 | Female | 34 | Adverse event |
| 01-710-1142 | Xanomeline High Dose | 76 | Female | 19 | Adverse event |
| 01-710-1278 | Xanomeline High Dose | 81 | Male | 65 | Adverse event |
| 01-711-1012 | Xanomeline High Dose | 67 | Female | 27 | Adverse event |
| 01-711-1433 | Xanomeline High Dose | 84 | Female | 10 | Adverse event |
| 01-713-1141 | Xanomeline High Dose | 79 | Male | 32 | Adverse event |
| 01-714-1425 | Xanomeline High Dose | 81 | Male | 5 | Study terminated by sponsor |
| 01-715-1319 | Xanomeline High Dose | 65 | Male | 17 | Withdrawal by subject |
| 01-715-1321 | Xanomeline High Dose | 75 | Female | 70 | Adverse event |
| 01-716-1030 | Xanomeline High Dose | 83 | Female | 6 | Withdrawal by subject |
| 01-716-1071 | Xanomeline High Dose | 78 | Female | 55 | Adverse event |
| 01-716-1189 | Xanomeline High Dose | 81 | Male | 142 | Adverse event |
| 01-716-1229 | Xanomeline High Dose | 73 | Female | 40 | Adverse event |
| 01-716-1373 | Xanomeline High Dose | 74 | Male | 76 | Adverse event |
| 01-717-1357 | Xanomeline High Dose | 77 | Male | 167 | Study terminated by sponsor |
| 01-718-1101 | Xanomeline High Dose | 82 | Male | 165 | Study terminated by sponsor |
| 01-718-1328 | Xanomeline High Dose | 86 | Male | 77 | Withdrawal by subject |
| 01-718-1371 | Xanomeline High Dose | 69 | Female | 98 | Adverse event |
| 01-718-1427 | Xanomeline High Dose | 74 | Female | 57 | Lack of efficacy |
| One row per subject. Reasons come from the disposition domain. | |||||
Appendix A — Listings
A.1 Individual subject data listings
| Subject | Treatment | Age (years) | Sex | Treatment duration (days) | End of study status |
|---|---|---|---|---|---|
| 01-701-1387 | Placebo | 87 | Female | 14 | Discontinued |
| 01-703-1175 | Placebo | 75 | Male | 7 | Discontinued |
| 01-704-1325 | Xanomeline Low Dose | 81 | Male | 73 | Discontinued |
| 01-703-1335 | Xanomeline High Dose | 67 | Female | 52 | Discontinued |
| 01-705-1382 | Xanomeline High Dose | 82 | Male | NA | Discontinued |
| 01-708-1372 | Xanomeline High Dose | 84 | Male | 8 | Discontinued |
| The pilot study ships no protocol deviation dataset, so this listing covers only violations severe enough to end study participation. Deviations that did not lead to discontinuation cannot be listed. | |||||
| Subject | Treatment | Age (years) | Age group | Sex | Race | Completed |
|---|---|---|---|---|---|---|
| 01-701-1015 | Placebo | 63 | 18-64 | Female | White | Yes |
| 01-701-1023 | Placebo | 64 | 18-64 | Male | White | No |
| 01-701-1047 | Placebo | 85 | >64 | Female | White | No |
| 01-701-1118 | Placebo | 52 | 18-64 | Male | White | Yes |
| 01-701-1130 | Placebo | 84 | >64 | Male | White | Yes |
| 01-701-1153 | Placebo | 79 | >64 | Female | White | Yes |
| 01-701-1203 | Placebo | 81 | >64 | Female | Black or african american | Yes |
| 01-701-1234 | Placebo | 69 | >64 | Male | White | Yes |
| 01-701-1345 | Placebo | 63 | 18-64 | Female | White | No |
| 01-701-1363 | Placebo | 81 | >64 | Female | Black or african american | Yes |
| 01-701-1387 | Placebo | 87 | >64 | Female | White | No |
| 01-701-1392 | Placebo | 78 | >64 | Male | White | Yes |
| 01-701-1415 | Placebo | 85 | >64 | Male | White | Yes |
| 01-701-1440 | Placebo | 70 | >64 | Male | White | Yes |
| 01-703-1042 | Placebo | 64 | 18-64 | Male | White | Yes |
| 01-703-1096 | Placebo | 81 | >64 | Female | White | No |
| 01-703-1100 | Placebo | 84 | >64 | Female | White | Yes |
| 01-703-1175 | Placebo | 75 | >64 | Male | White | No |
| 01-703-1210 | Placebo | 72 | >64 | Female | White | Yes |
| 01-703-1299 | Placebo | 81 | >64 | Female | White | Yes |
| 01-704-1010 | Placebo | 80 | >64 | Male | White | No |
| 01-704-1127 | Placebo | 84 | >64 | Female | White | Yes |
| 01-704-1164 | Placebo | 67 | >64 | Female | White | Yes |
| 01-704-1233 | Placebo | 87 | >64 | Female | White | No |
| 01-704-1260 | Placebo | 71 | >64 | Female | White | No |
| 01-704-1351 | Placebo | 70 | >64 | Male | White | Yes |
| 01-704-1388 | Placebo | 81 | >64 | Male | White | Yes |
| 01-704-1435 | Placebo | 74 | >64 | Male | White | No |
| 01-704-1445 | Placebo | 75 | >64 | Male | White | No |
| 01-705-1018 | Placebo | 69 | >64 | Female | White | No |
| 01-705-1059 | Placebo | 66 | >64 | Female | White | No |
| 01-705-1186 | Placebo | 84 | >64 | Female | White | No |
| 01-705-1282 | Placebo | 70 | >64 | Female | Black or african american | Yes |
| 01-705-1349 | Placebo | 86 | >64 | Female | White | Yes |
| 01-706-1041 | Placebo | 64 | 18-64 | Female | Black or african american | Yes |
| 01-707-1206 | Placebo | 65 | >64 | Male | White | Yes |
| 01-708-1087 | Placebo | 74 | >64 | Female | White | Yes |
| 01-708-1158 | Placebo | 81 | >64 | Female | White | No |
| 01-708-1171 | Placebo | 77 | >64 | Female | White | Yes |
| 01-708-1253 | Placebo | 61 | 18-64 | Male | White | Yes |
| 01-708-1286 | Placebo | 80 | >64 | Female | Black or african american | Yes |
| 01-708-1296 | Placebo | 57 | 18-64 | Male | Black or african american | Yes |
| 01-708-1316 | Placebo | 74 | >64 | Female | White | Yes |
| 01-708-1342 | Placebo | 59 | 18-64 | Female | White | Yes |
| 01-708-1378 | Placebo | 67 | >64 | Male | Black or african american | No |
| 01-709-1001 | Placebo | 76 | >64 | Female | White | Yes |
| 01-709-1088 | Placebo | 69 | >64 | Male | White | Yes |
| 01-709-1259 | Placebo | 82 | >64 | Male | White | No |
| 01-709-1301 | Placebo | 62 | 18-64 | Female | White | Yes |
| 01-709-1306 | Placebo | 60 | 18-64 | Female | White | No |
| 01-709-1312 | Placebo | 68 | >64 | Female | White | Yes |
| 01-709-1339 | Placebo | 81 | >64 | Male | White | Yes |
| 01-710-1027 | Placebo | 83 | >64 | Male | White | Yes |
| 01-710-1060 | Placebo | 82 | >64 | Male | White | Yes |
| 01-710-1077 | Placebo | 76 | >64 | Female | White | Yes |
| 01-710-1078 | Placebo | 81 | >64 | Female | White | Yes |
| 01-710-1083 | Placebo | 89 | >64 | Female | White | No |
| 01-710-1183 | Placebo | 80 | >64 | Female | White | Yes |
| 01-710-1264 | Placebo | 78 | >64 | Male | White | No |
| 01-710-1271 | Placebo | 86 | >64 | Female | White | No |
| 01-710-1314 | Placebo | 78 | >64 | Female | White | No |
| 01-710-1315 | Placebo | 83 | >64 | Female | White | No |
| 01-710-1368 | Placebo | 88 | >64 | Female | White | Yes |
| 01-711-1036 | Placebo | 70 | >64 | Male | Black or african american | Yes |
| 01-713-1179 | Placebo | 64 | 18-64 | Female | White | Yes |
| 01-713-1256 | Placebo | 71 | >64 | Male | White | Yes |
| 01-713-1269 | Placebo | 73 | >64 | Male | White | Yes |
| 01-714-1035 | Placebo | 88 | >64 | Female | White | Yes |
| 01-714-1375 | Placebo | 78 | >64 | Female | White | Yes |
| 01-715-1155 | Placebo | 59 | 18-64 | Female | White | No |
| 01-715-1207 | Placebo | 78 | >64 | Female | White | Yes |
| 01-715-1397 | Placebo | 76 | >64 | Female | White | Yes |
| 01-716-1024 | Placebo | 87 | >64 | Female | White | Yes |
| 01-716-1026 | Placebo | 73 | >64 | Female | White | Yes |
| 01-716-1044 | Placebo | 74 | >64 | Male | White | Yes |
| 01-716-1108 | Placebo | 86 | >64 | Female | White | Yes |
| 01-716-1160 | Placebo | 83 | >64 | Female | White | Yes |
| 01-716-1177 | Placebo | 72 | >64 | Male | White | Yes |
| 01-716-1308 | Placebo | 76 | >64 | Female | White | No |
| 01-716-1441 | Placebo | 85 | >64 | Male | White | Yes |
| 01-717-1201 | Placebo | 85 | >64 | Female | White | No |
| 01-717-1344 | Placebo | 64 | 18-64 | Female | White | No |
| 01-718-1139 | Placebo | 77 | >64 | Male | White | Yes |
| 01-718-1150 | Placebo | 73 | >64 | Female | White | Yes |
| 01-718-1172 | Placebo | 74 | >64 | Male | White | No |
| 01-718-1355 | Placebo | 79 | >64 | Male | White | Yes |
| 01-701-1033 | Xanomeline Low Dose | 74 | >64 | Male | White | No |
| 01-701-1097 | Xanomeline Low Dose | 68 | >64 | Male | White | Yes |
| 01-701-1111 | Xanomeline Low Dose | 81 | >64 | Female | White | No |
| 01-701-1115 | Xanomeline Low Dose | 84 | >64 | Male | White | No |
| 01-701-1188 | Xanomeline Low Dose | 71 | >64 | Male | White | No |
| 01-701-1192 | Xanomeline Low Dose | 80 | >64 | Female | White | Yes |
| 01-701-1211 | Xanomeline Low Dose | 76 | >64 | Female | White | No |
| 01-701-1294 | Xanomeline Low Dose | 67 | >64 | Male | White | No |
| 01-701-1317 | Xanomeline Low Dose | 68 | >64 | Male | White | Yes |
| 01-701-1324 | Xanomeline Low Dose | 79 | >64 | Male | White | Yes |
| 01-701-1341 | Xanomeline Low Dose | 51 | 18-64 | Male | White | No |
| 01-701-1429 | Xanomeline Low Dose | 84 | >64 | Female | White | No |
| 01-701-1442 | Xanomeline Low Dose | 57 | 18-64 | Female | Black or african american | Yes |
| 01-702-1082 | Xanomeline Low Dose | 84 | >64 | Female | White | No |
| 01-703-1086 | Xanomeline Low Dose | 71 | >64 | Male | White | No |
| 01-703-1119 | Xanomeline Low Dose | 81 | >64 | Female | White | No |
| 01-703-1182 | Xanomeline Low Dose | 84 | >64 | Male | White | No |
| 01-703-1197 | Xanomeline Low Dose | 76 | >64 | Female | Black or african american | No |
| 01-703-1279 | Xanomeline Low Dose | 72 | >64 | Female | White | No |
| 01-703-1379 | Xanomeline Low Dose | 81 | >64 | Female | Black or african american | Yes |
| 01-704-1009 | Xanomeline Low Dose | 83 | >64 | Male | White | No |
| 01-704-1025 | Xanomeline Low Dose | 81 | >64 | Female | White | No |
| 01-704-1114 | Xanomeline Low Dose | 77 | >64 | Male | White | No |
| 01-704-1120 | Xanomeline Low Dose | 71 | >64 | Female | White | No |
| 01-704-1135 | Xanomeline Low Dose | 74 | >64 | Female | White | Yes |
| 01-704-1218 | Xanomeline Low Dose | 81 | >64 | Female | White | Yes |
| 01-704-1323 | Xanomeline Low Dose | 68 | >64 | Female | White | No |
| 01-704-1325 | Xanomeline Low Dose | 81 | >64 | Male | White | No |
| 01-705-1031 | Xanomeline Low Dose | 56 | 18-64 | Female | White | No |
| 01-705-1199 | Xanomeline Low Dose | 87 | >64 | Male | White | No |
| 01-705-1292 | Xanomeline Low Dose | 60 | 18-64 | Female | Black or african american | Yes |
| 01-705-1393 | Xanomeline Low Dose | 84 | >64 | Female | White | No |
| 01-705-1431 | Xanomeline Low Dose | 68 | >64 | Female | White | Yes |
| 01-706-1384 | Xanomeline Low Dose | 74 | >64 | Female | White | No |
| 01-707-1037 | Xanomeline Low Dose | 72 | >64 | Female | White | No |
| 01-708-1019 | Xanomeline Low Dose | 68 | >64 | Male | White | No |
| 01-708-1032 | Xanomeline Low Dose | 62 | 18-64 | Male | White | No |
| 01-708-1084 | Xanomeline Low Dose | 73 | >64 | Female | White | Yes |
| 01-708-1272 | Xanomeline Low Dose | 82 | >64 | Male | White | No |
| 01-708-1297 | Xanomeline Low Dose | 61 | 18-64 | Male | White | No |
| 01-708-1348 | Xanomeline Low Dose | 79 | >64 | Female | White | Yes |
| 01-708-1353 | Xanomeline Low Dose | 87 | >64 | Female | Black or african american | No |
| 01-708-1428 | Xanomeline Low Dose | 84 | >64 | Female | White | No |
| 01-709-1007 | Xanomeline Low Dose | 54 | 18-64 | Female | White | No |
| 01-709-1020 | Xanomeline Low Dose | 72 | >64 | Female | White | Yes |
| 01-709-1081 | Xanomeline Low Dose | 86 | >64 | Female | White | No |
| 01-709-1102 | Xanomeline Low Dose | 71 | >64 | Female | White | No |
| 01-709-1217 | Xanomeline Low Dose | 77 | >64 | Male | White | No |
| 01-709-1285 | Xanomeline Low Dose | 87 | >64 | Male | White | No |
| 01-709-1326 | Xanomeline Low Dose | 75 | >64 | Female | White | Yes |
| 01-710-1002 | Xanomeline Low Dose | 88 | >64 | Male | White | No |
| 01-710-1045 | Xanomeline Low Dose | 83 | >64 | Female | White | No |
| 01-710-1053 | Xanomeline Low Dose | 84 | >64 | Female | White | No |
| 01-710-1154 | Xanomeline Low Dose | 84 | >64 | Male | White | No |
| 01-710-1166 | Xanomeline Low Dose | 81 | >64 | Female | White | No |
| 01-710-1235 | Xanomeline Low Dose | 56 | 18-64 | Female | White | Yes |
| 01-710-1270 | Xanomeline Low Dose | 83 | >64 | Female | White | No |
| 01-710-1300 | Xanomeline Low Dose | 78 | >64 | Female | White | No |
| 01-710-1358 | Xanomeline Low Dose | 82 | >64 | Male | White | No |
| 01-710-1385 | Xanomeline Low Dose | 77 | >64 | Male | White | No |
| 01-711-1143 | Xanomeline Low Dose | 76 | >64 | Female | White | No |
| 01-713-1043 | Xanomeline Low Dose | 78 | >64 | Female | White | Yes |
| 01-713-1073 | Xanomeline Low Dose | 74 | >64 | Female | Black or african american | Yes |
| 01-713-1448 | Xanomeline Low Dose | 71 | >64 | Female | White | No |
| 01-714-1068 | Xanomeline Low Dose | 79 | >64 | Female | White | No |
| 01-714-1195 | Xanomeline Low Dose | 75 | >64 | Male | White | Yes |
| 01-715-1085 | Xanomeline Low Dose | 77 | >64 | Female | White | Yes |
| 01-715-1107 | Xanomeline Low Dose | 65 | >64 | Male | White | No |
| 01-715-1405 | Xanomeline Low Dose | 69 | >64 | Male | White | No |
| 01-716-1063 | Xanomeline Low Dose | 80 | >64 | Male | White | No |
| 01-716-1094 | Xanomeline Low Dose | 82 | >64 | Male | White | No |
| 01-716-1103 | Xanomeline Low Dose | 79 | >64 | Male | White | Yes |
| 01-716-1151 | Xanomeline Low Dose | 83 | >64 | Female | White | No |
| 01-716-1157 | Xanomeline Low Dose | 85 | >64 | Male | White | Yes |
| 01-716-1167 | Xanomeline Low Dose | 68 | >64 | Male | White | Yes |
| 01-716-1298 | Xanomeline Low Dose | 76 | >64 | Female | White | No |
| 01-716-1311 | Xanomeline Low Dose | 78 | >64 | Male | White | No |
| 01-717-1004 | Xanomeline Low Dose | 80 | >64 | Female | White | Yes |
| 01-717-1446 | Xanomeline Low Dose | 75 | >64 | Female | White | Yes |
| 01-718-1066 | Xanomeline Low Dose | 79 | >64 | Female | White | No |
| 01-718-1079 | Xanomeline Low Dose | 67 | >64 | Female | White | No |
| 01-718-1170 | Xanomeline Low Dose | 80 | >64 | Female | White | No |
| 01-718-1250 | Xanomeline Low Dose | 82 | >64 | Female | White | No |
| 01-718-1254 | Xanomeline Low Dose | 78 | >64 | Male | White | Yes |
| 01-701-1028 | Xanomeline High Dose | 71 | >64 | Male | White | Yes |
| 01-701-1034 | Xanomeline High Dose | 77 | >64 | Female | White | Yes |
| 01-701-1133 | Xanomeline High Dose | 81 | >64 | Female | White | Yes |
| 01-701-1146 | Xanomeline High Dose | 75 | >64 | Female | White | No |
| 01-701-1148 | Xanomeline High Dose | 57 | 18-64 | Male | White | Yes |
| 01-701-1180 | Xanomeline High Dose | 56 | 18-64 | Male | White | No |
| 01-701-1181 | Xanomeline High Dose | 79 | >64 | Female | White | No |
| 01-701-1239 | Xanomeline High Dose | 56 | 18-64 | Male | White | Yes |
| 01-701-1275 | Xanomeline High Dose | 61 | 18-64 | Male | American indian or alaska native | No |
| 01-701-1287 | Xanomeline High Dose | 56 | 18-64 | Female | White | Yes |
| 01-701-1302 | Xanomeline High Dose | 61 | 18-64 | Male | White | No |
| 01-701-1360 | Xanomeline High Dose | 67 | >64 | Male | White | No |
| 01-701-1383 | Xanomeline High Dose | 72 | >64 | Female | White | Yes |
| 01-701-1444 | Xanomeline High Dose | 63 | 18-64 | Male | White | No |
| 01-703-1076 | Xanomeline High Dose | 69 | >64 | Male | White | No |
| 01-703-1258 | Xanomeline High Dose | 78 | >64 | Female | White | No |
| 01-703-1295 | Xanomeline High Dose | 88 | >64 | Female | White | No |
| 01-703-1335 | Xanomeline High Dose | 67 | >64 | Female | Black or african american | No |
| 01-703-1403 | Xanomeline High Dose | 67 | >64 | Male | White | No |
| 01-703-1439 | Xanomeline High Dose | 76 | >64 | Female | White | Yes |
| 01-704-1008 | Xanomeline High Dose | 76 | >64 | Female | White | No |
| 01-704-1017 | Xanomeline High Dose | 77 | >64 | Male | White | No |
| 01-704-1065 | Xanomeline High Dose | 75 | >64 | Male | White | No |
| 01-704-1074 | Xanomeline High Dose | 80 | >64 | Female | White | No |
| 01-704-1093 | Xanomeline High Dose | 79 | >64 | Male | White | No |
| 01-704-1241 | Xanomeline High Dose | 86 | >64 | Male | White | No |
| 01-704-1266 | Xanomeline High Dose | 82 | >64 | Male | White | No |
| 01-704-1332 | Xanomeline High Dose | 80 | >64 | Male | White | No |
| 01-705-1280 | Xanomeline High Dose | 56 | 18-64 | Female | White | Yes |
| 01-705-1281 | Xanomeline High Dose | 73 | >64 | Female | Black or african american | No |
| 01-705-1303 | Xanomeline High Dose | 72 | >64 | Male | White | No |
| 01-705-1310 | Xanomeline High Dose | 74 | >64 | Female | White | No |
| 01-705-1377 | Xanomeline High Dose | 63 | 18-64 | Female | Black or african american | No |
| 01-705-1382 | Xanomeline High Dose | 82 | >64 | Male | White | No |
| 01-706-1049 | Xanomeline High Dose | 60 | 18-64 | Female | White | No |
| 01-708-1178 | Xanomeline High Dose | 77 | >64 | Female | Black or african american | No |
| 01-708-1213 | Xanomeline High Dose | 76 | >64 | Female | White | No |
| 01-708-1216 | Xanomeline High Dose | 78 | >64 | Male | White | No |
| 01-708-1236 | Xanomeline High Dose | 86 | >64 | Female | White | No |
| 01-708-1336 | Xanomeline High Dose | 73 | >64 | Male | White | Yes |
| 01-708-1347 | Xanomeline High Dose | 61 | 18-64 | Female | White | No |
| 01-708-1372 | Xanomeline High Dose | 84 | >64 | Male | White | No |
| 01-708-1406 | Xanomeline High Dose | 71 | >64 | Female | White | Yes |
| 01-709-1029 | Xanomeline High Dose | 82 | >64 | Male | White | Yes |
| 01-709-1099 | Xanomeline High Dose | 79 | >64 | Female | White | Yes |
| 01-709-1168 | Xanomeline High Dose | 72 | >64 | Female | White | No |
| 01-709-1238 | Xanomeline High Dose | 69 | >64 | Male | White | No |
| 01-709-1309 | Xanomeline High Dose | 65 | >64 | Male | White | Yes |
| 01-709-1329 | Xanomeline High Dose | 70 | >64 | Male | White | No |
| 01-709-1424 | Xanomeline High Dose | 77 | >64 | Male | White | No |
| 01-710-1006 | Xanomeline High Dose | 77 | >64 | Male | White | Yes |
| 01-710-1021 | Xanomeline High Dose | 79 | >64 | Male | Black or african american | No |
| 01-710-1070 | Xanomeline High Dose | 85 | >64 | Female | White | No |
| 01-710-1137 | Xanomeline High Dose | 79 | >64 | Female | Black or african american | No |
| 01-710-1142 | Xanomeline High Dose | 76 | >64 | Female | White | No |
| 01-710-1187 | Xanomeline High Dose | 78 | >64 | Female | White | Yes |
| 01-710-1249 | Xanomeline High Dose | 79 | >64 | Male | White | Yes |
| 01-710-1278 | Xanomeline High Dose | 81 | >64 | Male | White | No |
| 01-710-1354 | Xanomeline High Dose | 73 | >64 | Male | White | Yes |
| 01-710-1408 | Xanomeline High Dose | 80 | >64 | Male | White | Yes |
| 01-711-1012 | Xanomeline High Dose | 67 | >64 | Female | White | No |
| 01-711-1433 | Xanomeline High Dose | 84 | >64 | Female | White | No |
| 01-713-1106 | Xanomeline High Dose | 74 | >64 | Male | White | Yes |
| 01-713-1141 | Xanomeline High Dose | 79 | >64 | Male | White | No |
| 01-713-1209 | Xanomeline High Dose | 77 | >64 | Female | White | Yes |
| 01-714-1288 | Xanomeline High Dose | 77 | >64 | Male | Black or african american | Yes |
| 01-714-1425 | Xanomeline High Dose | 81 | >64 | Male | White | No |
| 01-715-1319 | Xanomeline High Dose | 65 | >64 | Male | White | No |
| 01-715-1321 | Xanomeline High Dose | 75 | >64 | Female | White | No |
| 01-716-1030 | Xanomeline High Dose | 83 | >64 | Female | White | No |
| 01-716-1071 | Xanomeline High Dose | 78 | >64 | Female | White | No |
| 01-716-1189 | Xanomeline High Dose | 81 | >64 | Male | White | No |
| 01-716-1229 | Xanomeline High Dose | 73 | >64 | Female | White | No |
| 01-716-1364 | Xanomeline High Dose | 84 | >64 | Female | White | Yes |
| 01-716-1373 | Xanomeline High Dose | 74 | >64 | Male | White | No |
| 01-716-1418 | Xanomeline High Dose | 80 | >64 | Female | White | Yes |
| 01-716-1447 | Xanomeline High Dose | 72 | >64 | Female | White | Yes |
| 01-717-1109 | Xanomeline High Dose | 84 | >64 | Male | White | Yes |
| 01-717-1174 | Xanomeline High Dose | 73 | >64 | Male | White | Yes |
| 01-717-1357 | Xanomeline High Dose | 77 | >64 | Male | White | No |
| 01-718-1101 | Xanomeline High Dose | 82 | >64 | Male | Black or african american | No |
| 01-718-1328 | Xanomeline High Dose | 86 | >64 | Male | White | No |
| 01-718-1371 | Xanomeline High Dose | 69 | >64 | Female | White | No |
| 01-718-1427 | Xanomeline High Dose | 74 | >64 | Female | Black or african american | No |
| One row per subject, in treatment group and subject identifier order. | ||||||
| Subject | Treatment | Preferred term | System organ class | Onset day | Severity | Related | Outcome |
|---|---|---|---|---|---|---|---|
| 01-709-1424 | Xanomeline Low Dose | Syncope | Nervous system disorders | 5 | Moderate | Yes | Recovered/resolved |
| 01-718-1170 | Xanomeline Low Dose | Syncope | Nervous system disorders | 27 | Severe | Yes | Recovered/resolved |
| 01-718-1371 | Xanomeline High Dose | Partial seizures with secondary generalisation | Nervous system disorders | 38 | Severe | No | Recovered/resolved |
| Onset day is relative to the first dose of study drug. One row per event. | |||||||
| Subject | Treatment | Analyte | Visit | Worst post-baseline value | Upper limit of reference range | Multiple of upper limit |
|---|---|---|---|---|---|---|
| 01-705-1186 | Placebo | Alanine Aminotransferase (U/L) | Week 4 | 107.0 | 32.0 | 3.3 |
| 01-705-1186 | Placebo | Aspartate Aminotransferase (U/L) | Week 4 | 135.0 | 34.0 | 4.0 |
| 01-705-1186 | Placebo | Bilirubin (umol/L) | Unscheduled 4.1 | 124.8 | 21.0 | 5.9 |
| 01-708-1286 | Placebo | Alanine Aminotransferase (U/L) | Week 24 | 124.0 | 32.0 | 3.9 |
| 01-708-1286 | Placebo | Aspartate Aminotransferase (U/L) | Week 24 | 168.0 | 34.0 | 4.9 |
| 01-708-1286 | Placebo | Bilirubin (umol/L) | Week 16 | 8.5 | 21.0 | 0.4 |
| 01-705-1292 | Xanomeline Low Dose | Alanine Aminotransferase (U/L) | Week 12 | 88.0 | 34.0 | 2.6 |
| 01-705-1292 | Xanomeline Low Dose | Aspartate Aminotransferase (U/L) | Week 12 | 125.0 | 34.0 | 3.7 |
| 01-705-1292 | Xanomeline Low Dose | Bilirubin (umol/L) | Week 24 | 12.0 | 21.0 | 0.6 |
| 01-705-1310 | Xanomeline High Dose | Alanine Aminotransferase (U/L) | Week 8 | 129.0 | 32.0 | 4.0 |
| 01-705-1310 | Xanomeline High Dose | Aspartate Aminotransferase (U/L) | Week 8 | 114.0 | 34.0 | 3.4 |
| 01-705-1310 | Xanomeline High Dose | Bilirubin (umol/L) | Week 8 | 15.4 | 21.0 | 0.7 |
| 01-709-1029 | Xanomeline High Dose | Alanine Aminotransferase (U/L) | Week 26 | 18.0 | 35.0 | 0.5 |
| 01-709-1029 | Xanomeline High Dose | Aspartate Aminotransferase (U/L) | Week 24 | 27.0 | 36.0 | 0.8 |
| 01-709-1029 | Xanomeline High Dose | Bilirubin (umol/L) | Week 20 | 53.0 | 21.0 | 2.5 |
| One row per subject per analyte, showing the worst post-baseline value and its multiple of the upper limit of the reference range. Restricted to the analytes screened in the potential drug-induced liver injury table. | ||||||
A.2 Index of outputs
Every table, figure and listing of this report carries the ICH E3 output number that R/tlf-index.R holds for it. The index below lists them all, with the ICH E3 section each number belongs to and the population the output was computed on.
- Table 14.1.1
-
Analysis populations. ICH E3 section 14.1. Randomised population.
- Table 14.1.2
-
Subject disposition. ICH E3 section 14.1. Randomised population.
- Table 14.1.3
-
Demographic and baseline characteristics. ICH E3 section 14.1. Randomised population.
- Table 14.1.4
-
Medical history by body system and preferred term. ICH E3 section 14.1. Conditions reported by at least 5% of subjects in any treatment group, randomised population.
- Figure 14.1.1
-
Disposition of subjects from screening to study completion (Schulz et al. 2010). ICH E3 section 14.1.
- Table 14.2.1
-
Time to first dermatologic treatment-emergent adverse event. ICH E3 section 14.2. Intention-to-treat population.
- Table 14.2.1.1
-
Time to first dermatologic treatment-emergent adverse event (supportive analysis). ICH E3 section 14.2. Per-protocol population.
- Table 14.2.2
-
Change from baseline in supine systolic blood pressure at week 24. ICH E3 section 14.2. Safety population.
- Figure 14.2.1
-
Cumulative incidence of the first dermatologic treatment-emergent adverse event, intention-to-treat population. ICH E3 section 14.2.
- Figure 14.2.2
-
Hazard ratio for the primary endpoint by age group and sex, intention-to-treat population. ICH E3 section 14.2.
- Figure 14.2.3
-
Mean supine systolic blood pressure by visit and treatment group, safety population. ICH E3 section 14.2.
- Table 14.3.5
-
Extent of exposure. ICH E3 section 14.3. Safety population.
- Table 14.3.6
-
Prior and concomitant medications by drug class and preferred term. ICH E3 section 14.3. Medications taken by at least 5% of subjects in any treatment group, safety population.
- Table 14.3.1.1
-
Overview of treatment-emergent adverse events. ICH E3 section 14.3.1. Safety population.
- Table 14.3.1.2
-
Treatment-emergent adverse events by system organ class and preferred term. ICH E3 section 14.3.1. Events reported by at least 5% of subjects in any treatment group, safety population.
- Table 14.3.1.3
-
Treatment-emergent adverse events by maximum severity. ICH E3 section 14.3.1. Events reported by at least 5% of subjects in any treatment group, safety population.
- Table 14.3.1.4
-
Treatment-emergent adverse events by relationship to study drug. ICH E3 section 14.3.1. Events reported by at least 5% of subjects in any treatment group, safety population.
- Table 14.3.1.5
-
Serious treatment-emergent adverse events. ICH E3 section 14.3.1. Safety population.
- Table 14.3.4.1
-
Shift from baseline to worst post-baseline category. ICH E3 section 14.3.4. Alanine aminotransferase, safety population.
- Table 14.3.4.2
-
Shift from baseline to worst post-baseline category. ICH E3 section 14.3.4. Aspartate aminotransferase, safety population.
- Table 14.3.4.3
-
Shift from baseline to worst post-baseline category. ICH E3 section 14.3.4. Bilirubin, safety population.
- Table 14.3.4.4
-
Shift from baseline to worst post-baseline category. ICH E3 section 14.3.4. Creatinine, safety population.
- Table 14.3.4.5
-
Potential drug-induced liver injury. ICH E3 section 14.3.4. Safety population.
- Table 14.3.7
-
Shift from baseline to worst post-baseline category. ICH E3 section 14.3. Systolic blood pressure measured supine, safety population.
- Table 14.3.8
-
Shift from baseline to worst post-baseline category. ICH E3 section 14.3. QTcF interval, safety population.
- Listing 16.2.1.1
-
Subjects who discontinued the study. ICH E3 section 16.2.1. Randomised population.
- Listing 16.2.2.1
-
Subjects who discontinued for a protocol violation. ICH E3 section 16.2.2. Randomised population.
- Listing 16.2.4.1
-
Demographic data. ICH E3 section 16.2.4. Randomised population.
- Listing 16.2.7.1
-
Serious treatment-emergent adverse events. ICH E3 section 16.2.7. Safety population.
- Listing 16.2.8.1
-
Abnormal laboratory values meeting a liver-injury criterion. ICH E3 section 16.2.8. Safety population.