Table 2.
Change in Primary and Secondary Outcomes from Baseline to Week 78.*
| Outcome | Change from Baseline | Difference between Verubecestat Groups and Placebo Group in Mean Change† |
|||||
|---|---|---|---|---|---|---|---|
| Verubecestat 12-mg Group |
Verubecestat 40-mg Group |
Placebo Group |
Verubecestat 12-mg Group vs. Placebo Group (97.51% CI or 95% CI)‡ |
P Value§ | Verubecestat 40-mg Group vs. Placebo Group (97.51% CI or 95% CI)‡ |
P Value§ | |
| Primary | |||||||
| ADAS-cog score | 7.9±0.3 | 8.0±0.4 | 7.7±0.3 | 0.2 (−0.9 to 1.3) | 0.63 | 0.4 (−0.8 to 1.5) | 0.46 |
| ADCS-ADL score | −8.4±0.5 | −8.2±0.5 | −8.9±0.5 | 0.5 (−1.1 to 2.1) | 0.49 | 0.7 (−0.9 to 2.3) | 0.32 |
| Secondary | |||||||
| CDR-SB score | 2.1±0.1 | 2.1±0.1 | 2.1±0.1 | 0.0 (−0.4 to 0.3) | 0.0 (−0.3 to 0.4) | ||
| Hippocampal volume on MRI | |||||||
| No. of patients assessed | 308 | 281 | 308 | ||||
| % change | −5.6±0.1 | −5.7±0.1 | −5.0±0.1 | −0.6 (−1.0 to−0.2) | −0.7 (−1.1 to-0.3) | ||
| CSF concentration of total tau † | |||||||
| No. of patients assessed | 32 | 46 | 33 | ||||
| Magnitude of change | 1.02±0.03 | 1.04±0.02 | 1.07±0.03 | 0.95 (0.87 to 1.04) | 0.97 (0.90 to 1.05) | ||
| Cortical amyloid load on PET | |||||||
| No. of patients assessed | 20 | 10 | 14 | ||||
| Standardized uptake value ratio | −0.02±0.01 | −0.04±0.01 | 0.00±0.01 | −0.03 (−0.05 to 0.00) | −0.04 (−0.06 to −0.02) | ||
| MMSE score | −3.9±0.2 | −3.6±0.2 | −4.1±0.2 | 0.2 (−0.3 to 0.7) | 0.5 (0.0 to 1.0) | ||
| NPI score | 3.4±0.5 | 3.8±0.5 | 2.7±0.5 | 0.7 (−0.6 to 2.1) | 1.1 (−0.4 to 2.6) | ||
Plus-minus values are model-based least-squares means ±SE. This table summarizes data from patients in the primary population who received at least one dose of the trial regimen. For ADAS-cog (with scores ranging from 0 to 70), CDR-SB (with scores ranging from 0 to 18), and NPI (with scores ranging from 1 to 144), a higher positive mean change score corresponds to greater decline relative to baseline and a positive treatment difference favors placebo. For ADCS-ADL (with scores ranging from 0 to 78) and MMSE (with scores ranging from 0 to 30), a higher negative mean change score corresponds to greater decline relative to baseline and a positive treatment difference favors verubecestat. For biomarkers other than the CSF concentration of total tau, a negative mean change corresponds to a reduction in the biomarker value relative to baseline and a negative difference corresponds to a greater reduction with verubecestat than with placebo.
For the CSF concentration of total tau only, the change refers to the magnitude of the change and the difference refers to the ratio of the magnitude of the change with verubecestat to the magnitude of the change with placebo. The standard error is presented on the log scale. A magnitude of change greater than 1 indicates an increase in total tau relative to baseline, and a ratio of change in magnitude of less than 1 indicates a smaller increase with verubecestat than with placebo.
According to the strategy of adjustment for multiple testing, 97.51% confidence intervals are presented for all outcomes except for MMSE and NPI, for which 95% confidence intervals are presented.
According to the strategy of adjustment for multiple testing, formal hypothesis testing ceased within each dose level after the first hypothesis (which was based on the results of the ADAS-cog analysis) failed to be rejected.