Table 3.
Least-Squares Mean Percent Change from Baseline in Pharmacodynamic Variables at Day 84 after the First Dose in the Multiple-Dose Phase (Pharmacodynamic Population).*
| Variable | Placebo (N = 11) | Inclisiran
|
|||||
|---|---|---|---|---|---|---|---|
| 300 mg, with Statin (N = 3) | 300 mg, without Statin (N = 6) | 500 mg, with Statin (N = 5) | 500 mg, without Statin (N = 6) | 125 mg, without Statin (N = 6) | 250 mg, without Statin (N = 6) | ||
| PCSK9 | |||||||
| Percent change (95% CI) | 16.9 (−2.4 to 40.0) | −79.9 (−85.4 to −72.5)† | −71.8 (−77.4 to −64.8)† | −83.8 (−87.3 to −79.3)† | −81.5 (−85.2 to −76.9)† | −77.4 (−81.9 to −71.8)† | −75.7 (−80.5 to −69.6)† |
| Difference (percentage points) | — | −96.8 | −88.7 | −100.7 | −98.4 | −62.1 | −92.6 |
|
| |||||||
| LDL cholesterol | |||||||
| Percent change (95% CI) | −14.2 (−30.2 to 5.5) | −45.1 (−61.6 to −21.4)‡ | −59.7 (−68.7 to −48.1)† | −53.2 (−64.5 to −38.3)§ | −51.7 (−62.5 to −37.8)§ | −39.8 (−51.1 to −25.9) | −52.2 (−62.9 to −38.4)§ |
| Difference (percentage points) | — | −30.9 | −45.5 | −39.0 | −37.5 | −49.3 | −38.0 |
| Percent change at group nadir¶ | −14.2 | −51.6 | −59.7 | −58.8 | −53.9 | −45.0 | −55.5 |
|
| |||||||
| Total cholesterol | |||||||
| Percent change (95% CI) | −7.6 (−15.5 to 1.0) | −24.9 (−35.8 to −12.0)‡ | −40.4 (−46.7 to −33.4)† | −30.4 (−38.4 to −21.3)† | −27.0 (−34.7 to −18.3)§ | −23.8 (−31.9 to −14.7) | −34.5 (−41.4 to −26.7)† |
| Difference (percentage points) | — | −17.3 | −32.8 | −22.8 | −19.4 | −20.9 | −26.9 |
|
| |||||||
| HDL cholesterol | |||||||
| Percent change (95% CI) | 0.6 (−6.0 to 7.6) | 10.8 (−1.5 to 24.6) | 11.7 (2.7 to 21.4) | 5.3 (−3.9 to 15.3) | 12.8 (3.8 to 22.6)‡ | 12.9 (3.8 to 22.7) | 4.1 (−4.2 to 13.1) |
| Difference (percentage points) | — | 10.2 | 11.1 | 4.7 | 12.2 | −4.1 | 3.5 |
|
| |||||||
| Non-HDL cholesterol | |||||||
| Percent change (95% CI) | −10.6 (−21.3 to 1.6) | −35.7 (−48.7 to −19.3)‡ | −56.9 (−63.3 to −49.4)† | −46.2 (−54.9 to −35.8)† | −45.1 (−53.3 to −35.5)† | −36.9 (−46.3 to −25.9) | −45.3 (−53.4 to −35.8)† |
| Difference (percentage points) | — | −25.1 | −46.3 | −35.6 | −34.5 | −26.2 | −34.7 |
|
| |||||||
| Apolipoprotein B | |||||||
| Percent change (95% CI) | −12.8 (−23.2 to −1.0) | −37.2 (−49.8 to −21.4)‡ | −52.4 (−59.4 to −44.2)† | −41.8 (−51.1 to −30.7)† | −46.4 (−54.3 to −37.2)† | −33.3 (−43.1 to −21.8) | −46.5 (−54.3 to −37.3)† |
| Difference (percentage points) | — | −24.4 | −39.6 | −29.0 | −33.6 | −24.5 | −33.7 |
|
| |||||||
| Lipoprotein(a) | |||||||
| Percent change (95% CI) | −6.0 (−26.7 to 20.4) | −30.7 (−54.3 to 5.1) | −19.2 (−40.0 to 8.8) | −42.7 (−59.7 to −18.4)‡ | −27.4 (−45.8 to −2.7) | −22.7 (−28.4 to −16.5)‡ | −28.1 (−46.4 to −3.4) |
| Difference (percentage points) | — | −24.7 | −13.2 | −36.7 | −21.4 | −24.7 | −22.1 |
The analysis was performed with the use of a baseline-adjusted analysis of covariance (ANCOVA). Differences shown in the inclisiran groups are with the placebo group. Data for the 11 participants in the placebo group were pooled (3 participants were taking a stable dose of statins, and 8 were not). The 300-mg and 500-mg doses were administered as two monthly doses, the 125-mg dose was administered as four weekly doses, and the 250-mg dose was administered as once every 2 weeks for two doses. Values are from day 91 for the 125-mg group. P values were calculated with the use of the repeated-measures ANCOVA.
P<0.001 for the pairwise comparison with placebo.
P<0.05 for the pairwise comparison with placebo.
P<0.01 for the pairwise comparison with placebo.
The group nadir was defined as the largest mean percent reduction from the baseline value during the study.