Table 2. Secondary Efficacy End Points in the Intention-to-Treat Population.
| Least squares mean difference in change from baseline: alirocumab vs placebo, % (97.5% CI) | ||||
|---|---|---|---|---|
| Q2W cohort (n = 74) | P value | Q4W cohort (n = 79) | P value | |
| Key secondary end points a | ||||
| LDL-C to week 12 | −45.5 (−56.3 to −34.7) | <.001 | −41.5 (−52.7 to −30.2) | <.001 |
| Apolipoprotein B to week 24 | −37.8 (−47.5 to −28.2) | <.001 | −30.7 (−42.0 to −19.4) | <.001 |
| Non–HDL-C to week 24 | −40.7 (−52.2 to −29.1) | <.001 | −31.9 (−44.1 to −19.7) | <.001 |
| Total cholesterol to week 24 | −30.8 (−39.8 to −21.9) | <.001 | −23.3 (−33.5 to −13.1) | <.001 |
| Apolipoprotein B to week 12 | −38.9 (−48.2 to −29.6) | <.001 | −32.8 (−42.8 to −22.7) | <.001 |
| Non–HDL-C to week 12 | −42.8 (−53.8 to −31.8) | <.001 | −37.5 (−47.9 to −27.0) | <.001 |
| Total cholesterol to week 12 | −32.7 (−41.3 to −24.2) | <.001 | −27.9 (−35.6 to −20.2) | <.001 |
| Combined estimates for odds ratio (97.5% CI): alirocumab vs placebo | ||||
| LDL-C <130 mg/dL at week 24b | 77.6 (6.3 to 960.0) | .001 | 14.9 (3.2 to 69.8) | <.001 |
| LDL-C <130 mg/dL at week 12b | 26.5 (4.0 to 174.8) | <.001 | 40.9 (5.7 to 290.9) | <.001 |
| LDL-C <110 mg/dL at week 24 | 52.7 (3.5 to 804.3) | .001 | 43.1 (3.7 to 498.6) | <.001 |
| LDL-C <110 mg/dL at week 12–LOCF | 41.3 (6.6 to I)c | <.001 | 104.8 (5.2 to 2095.9) | <.001 |
| Adjusted mean difference (97.5% CI) in change from baseline: alirocumab vs placebo, % | ||||
| Lipoprotein(a) to week 24 | −15.2 (−30.3 to −0.1) | .02 | −24.9 (−44.4 to −5.4) | .004 |
| Lipoprotein(a) to week 12b | −5.6 (−21.7 to 10.4) | .43 | −13.5 (−32.7 to 5.7) | .11 |
| HDL-C to week 24d | 6.4 (0.5 to 12.3) | NA | 4.4 (−3.6 to 12.5) | NA |
| Fasting triglyceride to week 24e | 4.3 (−19.1 to 27.6) | NA | −19.0 (−41.5 to 3.5) | NA |
| Apolipoprotein A1 to week 24e | 1.1 (−5.9 to 8.2) | NA | 8.9 (1.3 to 16.5) | NA |
| HDL-C to week 12d | 5.6 (−3.1 to 14.3) | NA | 7.5 (−1.7 to 16.6) | NA |
| Fasting triglyceride to week 12e | −8.7 (−28.8 to 11.4) | NA | −8.1 (−31.3 to 15.1) | NA |
| Apolipoprotein A1 to week 12d | −1.6 (−7.4 to 4.1) | NA | 5.7 (−2.7 to 14.1) | NA |
Abbreviations: HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Q2W, dosing every 2 weeks; Q4W, dosing every 4 weeks; NA, not applicable.
Regarding secondary end points, the proportion of patients reaching 50% or greater reduction in LDL-C at week 24 was 21.6% in the alirocumab Q2W cohort (vs 0% in placebo) and 32.4% in the alirocumab Q4W cohort (vs 9.1% in placebo). At week 12, the proportion of patients reaching 50% or greater reduction in LDL-C was 25.2% in the alirocumab Q2W cohort (vs 0% in placebo) and 31.9% in the alirocumab Q4W cohort (vs 0.1% in placebo).
At the time this study was initiated, the pediatric LDL-C recommendation was <130 mg/dL. Continuous secondary efficacy end points anticipated to have a normal distribution were analyzed using the same approach as the primary end point; those anticipated to have a nonnormal distribution were analyzed using a multiple imputation approach followed by a robust regression model using M-estimation with treatment group and randomization strata as main effects and corresponding baseline value as covariate. Categorical secondary efficacy end points were analyzed using a multiple imputation approach followed by logistic regression model adjusting for treatment group as main effect and corresponding baseline value as covariate, stratified by randomization factors.
Exacts odds ratio vs placebo; hierarchical testing procedure did not establish significance.
Least squares mean difference.
Combined estimate for adjusted mean difference.