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The effect of LCZ696 (sacubitril/valsartan) on amyloid-β concentrations in cerebrospinal fluid in healthy subjects.

Langenickel TH, Tsubouchi C, Ayalasomayajula S, Pal P, Valentin MA, Hinder M, Jhee S, Gevorkyan H, Rajman I - Br J Clin Pharmacol (2016)

Bottom Line: LCZ696 had no significant effect on CSF AUEC(0,36 h) of the aggregable Aβ species 1-42 or 1-40 compared with placebo (estimated treatment ratios 0.98 [95% CI 0.73, 1.34; P = 0.919] and 1.05 [95% CI 0.82, 1.34; P = 0.702], respectively).LCZ696 did not cause changes in CSF levels of aggregable Aβ isoforms (1-42 and 1-40) compared with placebo, despite achieving CSF concentrations of LBQ657 sufficient to inhibit neprilysin.The clinical relevance of the increase in soluble CSF Aβ 1-38 is currently unknown.

View Article: PubMed Central - PubMed

Affiliation: Translational Medicine, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.

No MeSH data available.


Related in: MedlinePlus

Concentration of amyloid‐β isoforms by timepoint at baseline and on day 14 for LCZ696 (green lines) and placebo (blue lines) groups, (A) amyloid‐β 1–42 in cerebral spinal fluid, (B) amyloid‐β 1–40 in cerebral spinal fluid, (C) amyloid‐β 1–38 in cerebral spinal fluid and (D) amyloid‐β 1–40 in plasma
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bcp12861-fig-0001: Concentration of amyloid‐β isoforms by timepoint at baseline and on day 14 for LCZ696 (green lines) and placebo (blue lines) groups, (A) amyloid‐β 1–42 in cerebral spinal fluid, (B) amyloid‐β 1–40 in cerebral spinal fluid, (C) amyloid‐β 1–38 in cerebral spinal fluid and (D) amyloid‐β 1–40 in plasma

Mentions: Compared with placebo, LCZ696 treatment was not associated with a change from baseline to day 14 in CSF Aβ1–42 AUEC(0,36 h), when assessed by treatment comparison or visual inspection of the concentration time–profile (Table 2, Figure 1A). Similarly, there was no change from baseline in CSF Aβ1–40 AUEC(0,36 h) with LCZ696 compared with placebo (Table 2, Figure 1B).


The effect of LCZ696 (sacubitril/valsartan) on amyloid-β concentrations in cerebrospinal fluid in healthy subjects.

Langenickel TH, Tsubouchi C, Ayalasomayajula S, Pal P, Valentin MA, Hinder M, Jhee S, Gevorkyan H, Rajman I - Br J Clin Pharmacol (2016)

Concentration of amyloid‐β isoforms by timepoint at baseline and on day 14 for LCZ696 (green lines) and placebo (blue lines) groups, (A) amyloid‐β 1–42 in cerebral spinal fluid, (B) amyloid‐β 1–40 in cerebral spinal fluid, (C) amyloid‐β 1–38 in cerebral spinal fluid and (D) amyloid‐β 1–40 in plasma
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4834603&req=5

bcp12861-fig-0001: Concentration of amyloid‐β isoforms by timepoint at baseline and on day 14 for LCZ696 (green lines) and placebo (blue lines) groups, (A) amyloid‐β 1–42 in cerebral spinal fluid, (B) amyloid‐β 1–40 in cerebral spinal fluid, (C) amyloid‐β 1–38 in cerebral spinal fluid and (D) amyloid‐β 1–40 in plasma
Mentions: Compared with placebo, LCZ696 treatment was not associated with a change from baseline to day 14 in CSF Aβ1–42 AUEC(0,36 h), when assessed by treatment comparison or visual inspection of the concentration time–profile (Table 2, Figure 1A). Similarly, there was no change from baseline in CSF Aβ1–40 AUEC(0,36 h) with LCZ696 compared with placebo (Table 2, Figure 1B).

Bottom Line: LCZ696 had no significant effect on CSF AUEC(0,36 h) of the aggregable Aβ species 1-42 or 1-40 compared with placebo (estimated treatment ratios 0.98 [95% CI 0.73, 1.34; P = 0.919] and 1.05 [95% CI 0.82, 1.34; P = 0.702], respectively).LCZ696 did not cause changes in CSF levels of aggregable Aβ isoforms (1-42 and 1-40) compared with placebo, despite achieving CSF concentrations of LBQ657 sufficient to inhibit neprilysin.The clinical relevance of the increase in soluble CSF Aβ 1-38 is currently unknown.

View Article: PubMed Central - PubMed

Affiliation: Translational Medicine, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.

No MeSH data available.


Related in: MedlinePlus