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Quelle:
MEDLINE Abstract
Alzheimer-Therapie: Bisher schlugen alle Versuche fehl,
den Verlauf einer Alzheimer-Erkrankung mit Hilfe von Medikamenten
signifikant zu verbessern. Daher hat die hier vorgestellte Studie
eine große Bedeutung. Unter der Gabe 2 x täglich von 800 mg Tarenflurbil
gelang es bei den in die Studie eingeschlossenen Alzheimer-Patienten
im Vergleich zu einem Scheinmedikament ein Fortschreiten der den
Alltag beeinflussenden neurologischen Ausfälle zu verlangsamen.


Die
vollständige englischsprachige Kurzversion dieser Studie (sog.
MEDLINE Abstract) finden Sie
hier
Wilcock
GK, et al.
Efficacy
and safety of tarenflurbil in mild to moderate Alzheimer`s disease:
a randomised phase II trial.
Lancet
Neurol. 2008 Jun;7(6):483-93.
Epub
2008 Apr 29. PMID: 18450517
Abstract
BACKGROUND: The amyloid-beta peptide Abeta(42) has been
implicated in the pathogenesis of Alzheimer`s disease (AD). We
aimed to test the effects of tarenflurbil, a selective Abeta(42)-lowering
agent (SALA), on cognition and function in patients with mild
to moderate AD.
METHODS:
210 patients living in the community who had a mini-mental state
examination (MMSE) score of 15-26 were randomly assigned to receive
tarenflurbil twice per day (400 mg [n=69] or 800 mg [n=70]) or
placebo (n=71) for 12 months in a phase II, multicentre, double-blind
study.
FINDINGS:
A prespecified interaction analysis revealed that patients with
mild AD (baseline MMSE 20-26) and moderate AD (baseline MMSE 15-19)
responded differently to tarenflurbil in the ADAS-cog and the
ADCS-ADL (p>or=0.10); therefore, these groups were analysed
separately.
Patients
with mild AD in the 800 mg tarenflurbil group had lower rates
of decline than did those in the placebo group in activities of
daily living (ADCS-ADL
difference in slope 3.98 [95% CI 0.33 to 7.62] points per year,
effect size [reduction from placebo decline rate] 46.4%, Cohen`s
d 0.45; p=0.033) and global function (CDR-sb difference -0.80
[-1.57 to -0.03] points per year, effect size 35.7%, Cohen`s d
0.42; p=0.042); slowing of cognitive decline did not differ significantly
(ADAS-cog difference -1.36 [-4.07 to 1.36] points per year, effect
size 33.7%, Cohen`s d 0.20; p=0.327). In patients with moderate
AD, 800 mg tarenflurbil twice per day had no significant effects
on ADCS-ADL and ADAS-cog and had a negative effect on CDR-sb (-52%,
Cohen`s d -1.08; p=0.003).
The
most common adverse events were diarrhoea (in seven, nine, and
five patients in the 800 mg, 400 mg, and placebo groups, respectively),
nausea (in seven, seven, and four patients), and dizziness (in
five, nine, and four patients). Patients with mild AD who were
in the 800 mg tarenflurbil group for 24 months had lower rates
of decline for all three primary outcomes than did patients who
were in the placebo group for months 0-12 and a tarenflurbil group
for months 12-24 (all p<0.001), and had better outcomes than
did patients who were in the placebo group for months 0-12 and
the 800 mg tarenflurbil group for months 12-24 (all p<0.05).
INTERPRETATION: 800 mg tarenflurbil twice per day was well
tolerated for up to 24 months of treatment, with evidence of a
dose-related effect on measures of daily activities and global
function in patients with mild AD.
FUNDING:
Myriad Pharmaceuticals.
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