Table 3.
Changes in Laboratory Parameters from Baseline to Week 13/et
| Maralixibat 10 mg (n = 21) | Maralixibat 20 mg (n = 21) | Maralixibat Overall (n = 42) | Placebo (n = 24) | |
|---|---|---|---|---|
| Bile acid synthesis | ||||
| C4, ng/mL | ||||
| LS mean change from baseline (95% CI) | 21.5 | 5.5 | 13.5 | –2.2 |
| (10.9, 32.1)‡ | (–5.2, 16.2) | (6.0, 21.0)‡ | (–12.5, 8.1) | |
| LS mean difference from placebo (95% CI) | 23.7 | 7.7 | 15.7 | N/A |
| (8.9, 38.5)† | (–7.2, 22.7) | (2.9, 28.5)* | ||
| Potential regulators of bile acid synthesis | ||||
| FGF‐19, pg/mL | ||||
| LS mean change from baseline (95% CI) | 7.1 | –31.8 | –12.3 | –5.8 |
| (–31.1, 45.4) | (–70.9, 7.3) | (–39.3, 14.6) | (–42.5, 30.9) | |
| LS mean difference from placebo (95% CI) | 12.9 | –26.0 | –6.5 | N/A |
| (–39.7, 65.5) | (–80.8, 28.8) | (–52.6, 39.5) | ||
| FGF‐21, pg/mL | ||||
| LS mean change from baseline (95% CI) | –32.2 | 28.9 | –1.7 | 20.8 |
| (–99.7, 35.3) | (–33.6, 91.4) | (–47.1, 43.8) | (–39.3, 80.9) | |
| LS mean difference from placebo (95% CI) | –53.0 | 8.1 | –22.4 | N/A |
| (–143.5, 37.5) | (–78.5, 94.7) | (–97.8, 52.9) | ||
| Cholestasis | ||||
| ALP, U/L | ||||
| LS mean change from baseline (95% CI) | –7.4 | 17.1 | 4.9 | 7.3 |
| (–41.8, 27.0) | (–17.3, 51.5) | (–19.5, 29.2) | (–24.7, 39.3) | |
| LS mean difference from placebo (95% CI) | –14.7 | 9.8 | –2.4 | N/A |
| (–61.7, 32.3) | (–37.2, 56.8) | (–42.6, 37.8) | ||
| Autotaxin, ng/mL | ||||
| LS mean change from baseline (95% CI) | –167.7 | –82.5 | –125.1 | 62.8 |
| (–275.6, –59.8)† | (–188.9, 23.9) | (–201.1, –49.1)† | (–42.5, 168.1) | |
| LS mean difference from placebo (95% CI) | –230.5 | –145.3 | –187.9 | N/A |
| (–381.9, –79.0)† | (–296.1, 5.6) | (–318.8, –56.9)† | ||
| GGT, U/L | ||||
| LS mean change from baseline (95% CI) | 28.6 | 61.9 | 45.3 | 45.0 |
| (–46.5, 103.7) | (–13.1, 137.0) | (–7.7, 98.2) | (–24.6, 114.6) | |
| LS mean difference from placebo (95% CI) | –16.4 | 16.9 | 0.3 | N/A |
| (–118.7, 85.9) | (–85.5, 119.4) | (–87.2, 87.7) | ||
| Total bilirubin, mg/dL | ||||
| LS mean change from baseline (95% CI) | 0.00 | 0.09 | 0.04 | –0.05 |
| (–0.13, 0.13) | (–0.04, 0.21) | (–0.05, 0.13) | (–0.17, 0.07) | |
| LS mean difference from placebo (95% CI) | 0.05 | 0.14 | 0.09 | N/A |
| (–0.12, 0.22) | (–0.04, 0.31) | (–0.06, 0.24) | ||
| Conjugated bilirubin, mg/dL | ||||
| LS mean change from baseline (95% CI) | 0.004 | 0.05 | 0.03 | –0.01 |
| (–0.06, 0.07) | (–0.02, 0.11) | (–0.02, 0.07) | (–0.08, 0.05) | |
| LS mean difference from placebo (95% CI) | 0.02 | 0.06 | 0.04 | N/A |
| (–0.08, 0.11) | (–0.03, 0.15) | (–0.04, 0.12) | ||
| Hepatocellular injury | ||||
| ALT, U/L | ||||
| LS mean change from baseline (95% CI) | 0.7 | 1.7 | 1.2 | 1.1 |
| (–12.7, 14.1) | (–11.8, 15.3) | (–8.3, 10.8) | (–11.5, 13.7) | |
| LS mean difference from placebo (95% CI) | –0.4 | 0.6 | 0.1 | N/A |
| (–18.7, 18.0) | (–18.0, 19.3) | (–15.7, 16.0) | ||
| AST, U/L | ||||
| LS mean change from baseline (95% CI) | –5.4 | 0.9 | –2.3 | 5.7 |
| (–18.9, 8.0) | (–12.7, 14.4) | (–11.9, 7.3) | (–7.0, 18.4) | |
| LS mean difference from placebo (95% CI) | –11.2 | –4.9 | –8.0 | N/A |
| (–29.8, 7.5) | (–23.7, 13.9) | (–24.1, 8.1) | ||
| Lipid metabolism | ||||
| Total cholesterol, mg/mL | ||||
| LS mean change from baseline (95% CI) | –15.4 | –6.3 | –10.9 | 2.3 |
| (–28.2, –2.7)* | (–18.8, 6.2) | (–19.7, –2.0)* | (–9.4, 14.0) | |
| LS mean difference from placebo (95% CI) | –17.7 | –8.6 | –13.2 | N/A |
| (–35.1, –0.4)* | (–25.7, 8.5) | (–27.8, 1.5) | ||
| LDL‐C, mg/mL | ||||
| LS mean change from baseline (95% CI) | –13.7 | –11.6 | –12.6 | –4.0 |
| (–24.2, –3.1)* | (–21.7, –1.5)* | (–19.8, –5.4)‡ | (–13.6, 5.6) | |
| LS mean difference from placebo (95% CI) | –9.6 | –7.5 | –8.6 | N/A |
| (–24.1, 4.8) | (–21.4, 6.3) | (–20.7, 3.5) | ||
*
P < 0.05, † P < 0.01, ‡ P < 0.001 (analysis of covariance model with treatment group, ALP level [strata] and treatment group by ALP level interaction as factors, and baseline value as a covariate). All P values are nominal (not adjusted for multiplicity).
Abbreviation: N/A, not applicable.