Trial reportAlzheimer's research & therapy2021
Safety, pharmacokinetics and exploratory pro-cognitive effects of HTL0018318, a selective M
Trial report in Alzheimer's research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed.
- Effectiveness of KarXT (xanomeline-trospium) for cognitive impairment in schizophrenia: post hoc analyses from a randomised, double-blind, placebo-controlled phase 2 study.Translational psychiatry · 2022Trial
- Safety and Pharmacokinetics of HTL0018318, a Novel MDrugs in R&D · 2021Trial
- Exploring Adjunctive Novel Therapeutic Approach of KarXT (Xanomeline-Trospium Chloride) for Managing Psychotic Symptoms in Patients With Schizophrenia and Alzheimer's Disease.Brain and behavior · 2026Review
- A New Era of Muscarinic Acetylcholine Receptor Modulators in Neurological Diseases, Cancer and Drug Abuse.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Muscarinic control of cardiovascular function in humans: a review of current clinical evidence.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2024Review
- Lewy Body Dementia: An Overview of Promising Therapeutics.Current neurology and neuroscience reports · 2023Review
- Modulation of Muscarinic Signalling in the Central Nervous System by Steroid Hormones and Neurosteroids.International journal of molecular sciences · 2022Review
- Reduced expression of the psychiatric risk gene DLG2 (PSD93) impairs hippocampal synaptic integration and plasticity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Targeting the M1 muscarinic acetylcholine receptor in Alzheimer's disease.Neuronal signaling · 2022Review
- Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders.Biomedicines · 2022Review
- The Basal Forebrain Cholinergic Nuclei and Their Relevance to Schizophrenia and Other Psychotic Disorders.Frontiers in psychiatry · 2022Review
- A phase 1b/2a multicenter study of the safety and preliminary pharmacodynamic effects of selective muscarinic MAlzheimer's & dementia (New York, N. Y.) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe cholinergic system and M
methodsThis randomised, double blind, placebo-controlled study was performed, investigating oral doses of 15-35 mg/day HTL0018318 or placebo in 7 cohorts of healthy younger adult (n = 36; 3 cohorts) and elderly (n = 50; 4 cohorts) subjects. Safety, tolerability and pharmacokinetic measurements were performed. Pharmacodynamics were assessed using a battery of neurocognitive tasks and electrophysiological biomarkers of synaptic and cognitive functions.
resultsHTL0018318 was generally well-tolerated in multiple doses up to 35 mg/day and were associated with mild or moderate cholinergic adverse events. There were modest increases in blood pressure and pulse rate when compared to placebo-treated subjects, with tendency for the blood pressure increase to attenuate with repeated dosing. There were no clinically significant observations or changes in blood and urine laboratory measures of safety or abnormalities in the ECGs and 24-h Holter assessments. HTL0018318 plasma exposure was dose-proportional over the range 15-35 mg. Maximum plasma concentrations were achieved after 1-2 h. The apparent terminal half-life of HTL0018318 was 16.1 h (± 4.61) in younger adult subjects and 14.3 h (± 2.78) in elderly subjects at steady state. HTL0018318 over the 10 days of treatment had significant effects on tests of short-term (working) memory (n-back) and learning (Milner maze) with moderate to large effect sizes.
conclusionMultiple doses of HTL0018138 showed well-characterised pharmacokinetics and were safe and generally well-tolerated in the dose range studied. Pro-cognitive effects on short-term memory and learning were demonstrated across the dose range. These data provide encouraging data in support of the development of HTL0018138 for cognitive dysfunction in AD and DLB.
trial registrationNetherlands Trial Register identifier NTR5781 . Registered on 22 March 2016.
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