Trial reportClinical drug investigation2012
Effects of single doses of avagacestat (BMS-708163) on cerebrospinal fluid Aβ levels in healthy young men.
Trial report in Clinical drug investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Impact of frequent cerebrospinal fluid sampling on Aβ levels: systematic approach to elucidate influencing factors.Alzheimer's research & therapy · 2016Trial
- Synthesize heterogeneous biological knowledge via representation learning for Alzheimer's disease drug repurposing.iScience · 2023Article
- Advances in PPARs Molecular Dynamics and Glitazones as a Repurposing Therapeutic Strategy through Mitochondrial Redox Dynamics against Neurodegeneration.Current neuropharmacology · 2022Review
- Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer's disease.Inflammopharmacology · 2019Review
- Drug Development for Alzheimer's Disease: Microglia Induced Neuroinflammation as a Target?International journal of molecular sciences · 2019Review
- Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · 2018Review
- Inhibition of γ-Secretase Leads to an Increase in Presenilin-1.Molecular neurobiology · 2018Article
- A Translational Systems Pharmacology Model for Aβ Kinetics in Mouse, Monkey, and Human.CPT: pharmacometrics & systems pharmacology · 2017Article
- Amyloid beta modulators and neuroprotection in Alzheimer's disease: a critical appraisal.Drug discovery today · 2017Review
- Current Research Therapeutic Strategies for Alzheimer's Disease Treatment.Neural plasticity · 2016Review
- Review
- Fluid Biomarkers in Clinical Trials of Alzheimer's Disease Therapeutics.Frontiers in neurology · 2015Review
- Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases.Nature reviews. Neurology · 2015Review
- Interpreting Alzheimer's disease clinical trials in light of the effects on amyloid-β.Alzheimer's research & therapy · 2014Review
- γ-Secretase inhibitors and modulators.Biochimica et biophysica acta · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe concentration of amyloid β (Aβ) peptides in cerebrospinal fluid (CSF) is a biomarker for Alzheimer's disease (AD) pathology, and has been used to evaluate the effectiveness of γ-secretase inhibition. Avagacestat is a selective γ-secretase inhibitor in development for the treatment of AD. The primary objective of this study was to assess the effects of single oral doses of avagacestat on the CSF Aβ concentrations in healthy male subjects. Secondary objectives included single-dose pharmacokinetics in CSF and plasma, safety and tolerability.
methodsThis was a double-blind, placebo-controlled, randomized, single-dose study. Healthy male subjects were assigned to one of three sequential avagacestat dose panels (50, 200 and 400 mg) or placebo as single oral doses.
results34 subjects were enrolled. Administration of a single dose of 200 or 400 mg of avagacestat resulted in a marked decrease in CSF Aβ(1-38), Aβ(1-40) and Aβ(1-42) concentrations vs placebo; with smaller decreases observed in the 50 mg dose group. Avagacestat was quickly absorbed into the systemic circulation, with a mean time to reach maximum plasma concentration (t(max)) of approximately 1-2 h, and a CSF t(max) of approximately 3 h. Adverse events were uncommon and occurred with similar frequency in the placebo and avagacestat groups.
conclusionAvagacestat was safe, well tolerated, and resulted in a notable decrease in CSF Aβ concentrations, suggestive of γ-secretase inhibition. The results warrant further clinical study in patients with AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.