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Alzheimers Dement. 2014 Oct;10(5 Suppl):S364-73. doi: 10.1016/j.jalz.2013.09.010. Epub 2014 Jan 10.

Efficacy and safety evaluation of HSD-1 inhibitor ABT-384 in Alzheimer's disease.

Author information

1
Global Pharmaceutical R&D, AbbVie, Inc., North Chicago, IL, USA. Electronic address: gerard.marek@abbvie.com.
2
Global Pharmaceutical R&D, AbbVie, Inc., North Chicago, IL, USA.

Abstract

BACKGROUND:

In this study we assessed increased cortisol in Alzheimer's disease (AD) patients. The selective 11-β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor ABT-384 blocked regeneration of active cortisol and this tests the hypothesis that intracellular hypercortisolism contributes to cognitive impairment.

METHODS:

In this double-blind, placebo- and active-controlled phase II study we examine the efficacy and safety of ABT-384 given 10 mg or 50 mg once daily, donepezil 10 mg once daily, or placebo for 12 weeks in subjects with mild-to-moderate AD. The primary efficacy end point was the change from baseline to final evaluation on the 13-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) total score.

RESULTS:

The study was terminated for futility after randomization of 267 subjects. ABT-384 did not improve ADAS-Cog scores or any secondary end point; however, donepezil significantly improved both cognition and functional end points. Overall incidence of adverse events was similar among treatment groups.

CONCLUSION:

ABT-384, when tested at doses associated with complete brain HSD-1 inhibition, did not produce symptomatic improvement in AD.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01137526.

KEYWORDS:

11-β-hydroxysteroid dehydrogenase; Alzheimer's disease; Clinical trial; Cognition; Cortisol; Dementia; Donepezil; Enzyme inhibitor; Glucocorticoids; Hypothalamic–pituitary–adrenal axis

PMID:
24418055
DOI:
10.1016/j.jalz.2013.09.010
[Indexed for MEDLINE]
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