Table 5.
Mean percent change from baseline to Day 15 (2-sided 80% CI) in CSF levels of Aβ fragments, sAβPPα, and sAβPPβ in healthy adults treated with multiple-ascending doses of PF-06751979 in studies B8271001 and B8271004
| CSF fragment | Percent change from baseline (2-sided 80% CI) | Placebo-adjusted percent change from baseline (2-sided 80% CI) | ||||||
| Study B8271001 | Study B8271004 | Study B8271001 | Study B8271004 | |||||
| Pooled PBO | PF-06751979 | Pooled | PF-06751979 | PF-06751979 | PF-06751979 | PF-06751979 | PF-06751979 | |
| (N = 4) | 50 mg (N = 8) | (N = 6) | 125 mg (N = 12) | 275 mg (N = 8) | 50 mg (N = 8) | 125 mg (N = 12) | 275 mg (N = 8) | |
| Aβ1–38 | –2.9 (–12.48, 7.63) | –58.4 (–61.34, –55.28) | –4.2 (–12.33, 4.63) | –80.3 (–81.51, –79.06) | –87.9 (–88.82, –86.98) | –57.2 (–62.28, –51.34) | –79.5 (–81.56, –77.11) | –87.4 (–88.80, –85.84) |
| Aβ1–40 | –6.5 (–24.69, 16.18) | –70.2 (–74.20, –65.52) | –10.0 (–18.48, –0.71) | –85.5 (–86.45, –84.38) | –92.9 (–93.54, –92.25) | –68.1 (–75.87, –57.86) | –83.8 (–85.65, –81.78) | –92.1 (–93.15, –90.98) |
| Aβ1–42 | –6.9 (–20.86, 9.61) | –71.9 (–74.97, –68.57) | –10.3 (–19.21, –0.48) | –86.4 (–87.40, –85.28) | –93.6 (–94.22, –92.93) | –69.9 (–75.38, –63.15) | –84.8 (–86.64, –82.74) | –92.9 (–93.85, –91.74) |
| Aβ total | –9.8 (–18.95, 0.30) | –64.0 (–66.62, –61.25) | –7.9 (–13.71, –1.73) | –80.1 (–81.01, –79.18) | –86.5 (–87.26, –85.74) | –60.1 (–65.03, –54.49) | –78.4 (–80.06, –76.62) | –85.4 (–86.57, –84.05) |
| Aβx-38 | –0.9 (–12.16, 11.87) | –60.2 (–63.42, –56.67) | –12.4 (–20.19, –3.77) | –82.0 (–83.18, –80.74) | –90.1 (–90.91, –89.23) | –59.8 (–65.42, –53.36) | –79.5 (–81.69, –76.96) | –88.7 (–90.06, –87.18) |
| Aβx-40 | 2.8 (–9.29, 16.49) | –60.4 (–63.71, –56.76) | –9.8 (–17.46, –1.40) | –81.0 (–82.16, –79.76) | –87.6 (–88.55, –86.62) | –61.5 (–66.98, –55.01) | –78.9 (–81.11, –76.52) | –86.3 (–87.82, –84.55) |
| Aβx-42 | –3.0 (–14.10, 9.64) | –64.3 (–67.21, –61.11) | –10.9 (–17.00, –4.29) | –81.9 (–82.76, –80.91) | –86.6 (–87.43, –85.76) | –63.2 (–68.37, –57.21) | –79.6 (–81.36, –77.78) | –85.0 (–86.34, –83.50) |
| sAβPPα | –9.9 (–18.34, –0.69) | 48.4 (38.56, 58.98) | –8.2 (–15.85, 0.06) | 58.7 (48.89, 69.05) | 81.7 (67.79, 96.85) | 64.8 (46.09, 85.94) | 72.9 (55.37, 92.40) | 98.0 (75.92, 122.96) |
| sAβPPβ | –13.8 (–20.39, –6.56) | –70.6 (–72.23, –68.93) | –5.6 (–12.11, 1.49) | –81.3 (–82.21, –80.27) | –84.3 (–85.28, –83.26) | –65.9 (–69.15, –62.40) | –80.2 (–81.84, –78.33) | –83.4 (–84.92, –81.69) |
Aβ, amyloid-β; CI, confidence interval; CSF, cerebrospinal fluid; sAβPP, soluble AβPP.