Table 1.
Demographic and Baseline Clinical Characteristics.*
| Characteristic | Verubecestat 12-mg Group (N = 652) |
Verubecestat 40-mg Group (N = 652) |
Placebo Group (N = 653) |
|---|---|---|---|
| Demographics | |||
| Age — yr | 71.3±7.4 | 71.8±7.6 | 72.4±7.6 |
| Female sex — no. (%) | 350 (53.7) | 379 (58.1) | 354 (54.2) |
| Race — no.(%)† | |||
| White | 523 (80.2) | 511 (78.4) | 532 (81.5) |
| Asian | 113 (17.3) | 120 (18.4) | 109 (16.7) |
| Other | 11 (1.7) | 14 (2.1) | 10 (1.5) |
| Data not reported | 5 (0.8) | 7 (1.1) | 2 (0.3) |
| Geographic region — no. (%) | |||
| United States or Canada | 269 (41.3) | 271 (41.6) | 270 (41.3) |
| Europe, Australia, or New Zealand | 203 (31.1) | 201 (30.8) | 203 (31.1) |
| Japan | 92 (14.1) | 89 (13.7) | 90 (13.8) |
| Other | 88 (13.5) | 91 (14.0) | 90 (13.8) |
| APOE4 carrier — no. (%) | 424 (65.0) | 400 (61.3) | 415 (63.6) |
| Alzheimer’s disease of mild severity, as evidenced by MMSE score of ≥21 — no. (%)‡ | 318 (48.8) | 305 (46.8) | 314 (48.1) |
| Treatment with acetylcholinesterase inhibitor, memantine, or both for Alzheimer’s disease — no. (%) | 576 (88.3) | 576 (88.3) | 583 (89.3) |
| Educational level below undergraduate degree — no. (%) | 392 (60.1) | 390 (59.8) | 394 (60.3) |
| Positive biomarker test for Alzheimer’s disease — no./total no. (%) | |||
| According to PET§ | 43/47 (91.5) | 23/25 (92.0) | 30/34 (88.2) |
| According to CSF analysis¶ | 54/56 (96.4) | 67/72 (93.1) | 50/55 (90.9) |
| Clinical outcome measures∥ | |||
| ADAS-cog | |||
| No. of patients assessed | 631 | 626 | 644 |
| Score | 21.3±7.5 | 21.4±7.6 | 21.7±7.6 |
| ADCS-ADL | |||
| No. of patients assessed | 627 | 622 | 636 |
| Score | 63.1±9.4 | 62.9±9.9 | 62.1±10.5 |
| CDR-SB | |||
| No. of patients assessed | 611 | 600 | 623 |
| Score | 5.4±2.1 | 5.4±2.1 | 5.6±2.3 |
| MMSE | |||
| No. of patients assessed | 610 | 600 | 628 |
| Score | 20.4±3.3 | 20.2±3.3 | 20.3±3.3 |
| NPI | |||
| No. of patients assessed | 632 | 631 | 639 |
| Score | 8.8±10.6 | 8.2±9.6 | 9.3±11.7 |
| Biomarkers∥ | |||
| Hippocampal volume on MRI — μl | |||
| No. of patients assessed | 308 | 281 | 308 |
| Value | 5875±1217 | 5795±1194 | 5812±1067 |
| CSF concentration of total tau — pg/ml | |||
| No. of patients assessed | 32 | 46 | 33 |
| Value | 211±95 | 243±120 | 254±211 |
| Cortical amyloid load on PET — standardized uptake value ratio | |||
| No. of patients assessed | 20 | 10 | 14 |
| Value | 0.89±0.10 | 0.87±0.11 | 0.88±0.11 |
Plus-minus values are means ±SD. This table summarizes data from patients in the primary population who received at least one dose of the trial regimen. The primary population included all patients who underwent randomization except the first 200 patients enrolled in the study and the patients who were randomly assigned to receive the 60-mg dose of verubecestat. Data from 1 patient in the 12-mg group who did not receive the trial regimen were excluded from this summary. Percentages may not sum to 100 because of rounding.
Race was reported by the patient.
Scores on the Mini–Mental State Examination (MMSE) range from 0 to 30, with lower scores indicating poorer cognitive performance.
The patient’s diagnosis was based on the visual read of a positron-emission tomography (PET) scan with 18F-flutemetamol that was performed according to the product label.
The patient’s diagnosis was based on the cerebrospinal fluid (CSF) concentration of tau or Aβ−42 with a cutoff level of 0.215.21
Results are provided for patients who were included in the full-analysis set. This subgroup consisted of patients who received at least one dose of the trial regimen and who had a baseline measurement and at least one postrandomization outcome measurement that was obtained within a window of ±6 weeks of a scheduled assessment visit. The number of patients analyzed differed depending on the particular outcome measure assessed. Alzheimer’s Disease Assessment Scale (ADAS-cog) scores range from 0 to 70, with higher scores indicating worse dementia. Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) scores range from 0 to 78, with lower scores indicating worse function. Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) scores range from 0 to 18, with higher scores indicating worse dementia. Neuropsychiatric Inventory (NPI) scores range from 1 to 144, with higher scores indicating more severe symptoms. MRI, CSF measurements, and PET were performed in a subgroup of patients.