Table 2.
Efficacy Results (Modified Intention-to-Treat Population).*
| Outcome | Least-Squares Mean Change per Month† | Least-Squares Mean at Week 24† | Estimated Percentage of Patients with Event | Hazard Ratio (95% CI)‡ | ||||
|---|---|---|---|---|---|---|---|---|
| Sodium Phenylbutyrate–Taurursodiol (N = 87) | Placebo (N = 48) | Sodium Phenylbutyrate–Taurursodiol (N = 87) | Placebo (N = 48) | Least-Squares Difference (95% Cl)†§ | Sodium Phenylbutyrate–Taurursodiol (N = 87) | Placebo (N = 48) | ||
| Primary outcome | ||||||||
| ALSFRS-R total score | −1.24±0.12 | −1.66±0.16 | 29.06±0.78 | 26.73±0.98 | 2.32 (0.18 to 4.47)¶ | |||
| Secondary outcomes: continuous | ||||||||
| ATLIS total score — % of predicted normal value‖ | −3.03±0.19 | −3.54±0.26 | 39.08±1.99 | 36.26±2.22 | 2.82 (−0.67 to 6.31) | |||
| ATLIS upper-limb score — % of predicted normal value‖** | −3.04±0.23 | −3.81±0.31 | 36.63±2.32 | 32.36±2.59 | 4.27 (0.16 to 8.38) | |||
| ATLIS lower-limb score — % of predicted normal value‖** | −2.98±0.24 | −3.36±0.33 | 41.17±2.37 | 39.09±2.66 | 2.09 (−2.23 to 6.41) | |||
| Plasma pNF-H level — pg/ml | 3.58±3.19 | −2.34±4.20 | 406.95±35.82 | 374.25±38.81 | 32.70 (−24.34 to 89.75) | |||
| Slow vital capacity — % of predicted normal value | −3.10±0.31 | −4.03±0.42 | 66.17±2.33 | 61.06±2.81 | 5.11 (−0.54 to 10.76) | |||
| Secondary outcomes: survival | ||||||||
| Death, tracheostomy, or hospitalization†† | 19.3±4.2 | 33.1±6.9 | 0.53 (0.27 to 1.05) | |||||
| Death or tracheostomy†† | 2.8±1.7 | 4.4±3.0 | 0.63 (0.11 to 3.92) | |||||
| Hospitalization | 17.5±4.1 | 29.7±6.6 | 0.54 (0.27 to 1.12) | |||||
Plus–minus values are means, differences, or percentages ±SE. The term pNF-H denotes phosphorylated axonal neurofilament H subunit.
Least squares denotes a mean or difference adjusted for terms in the model.
The hazard ratio is for sodium phenylbutyrate–taurursodiol as compared with placebo.
The difference was calculated as the value in the sodium phenylbutyrate–taurursodiol group minus the value in the placebo group. Unadjusted 95% confidence intervals are shown.
P = 0.03; no other P values are reported, in accordance with the prespecified hierarchical order of outcomes.
The numbers of participants who are represented at week 24 are as follows: 32 in the placebo group and 55 in the sodium phenylbutyrate–taurursodiol group for the ATLIS total score; 32 and 55, respectively, for the ATLIS upper-limb score; and 33 and 56, respectively, for the ATLIS lower-limb score. For the numbers of participants in each group at other time points, see Figure S5A through S5C in the Supplementary Appendix.
These are presented as exploratory outcomes.
These secondary outcomes encompassed time to death, tracheostomy, permanent assisted ventilation, or hospitalization and time to death, tracheostomy, or permanent assisted ventilation (as described in the protocol). One tracheostomy occurred in the placebo group; there were no instances of permanent assisted ventilation delivered by noninvasive means.