Evidence map›Paper›PMID 35229025›Full record

ArticleAlzheimer's & dementia (New York, N. Y.)2022

A phase 1b/2a multicenter study of the safety and preliminary pharmacodynamic effects of selective muscarinic M

Pradeep J Nathan, S Babli Millais, Alex Godwood, Odile Dewit, David M Cross, Janet Liptrot, Bharat Ruparelia, Stephen Paul Jones, Geor Bakker, Paul T Maruff and 5 more

Open access · goldAbstract read
In one paragraph

Article in Alzheimer's & dementia (New York, N. Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 40% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Sex, Age, and Regional Differences inCurrent neuropharmacology · 2023
    Article
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 2 countries.

Pradeep J NathanHeptares Therapeutics Ltd Cambridge UK.ORCID https://orcid.org/0000-0003-0943-5329
S Babli MillaisHeptares Therapeutics Ltd Cambridge UK.ORCID https://orcid.org/0000-0002-1824-3444
Alex GodwoodHeptares Therapeutics Ltd Cambridge UK.
Odile DewitHeptares Therapeutics Ltd Cambridge UK.
David M CrossCross Pharma Consulting Limited Cambridge UK.
Janet LiptrotHeptares Therapeutics Ltd Cambridge UK.
Bharat RupareliaHeptares Therapeutics Ltd Cambridge UK.
Stephen Paul JonestranScrip Partners LLP Wokingham UK.
Geor BakkerHeptares Therapeutics Ltd Cambridge UK.
Paul T MaruffCogstate Ltd New Haven Connecticut USA.
Gregory A LightDepartment of Psychiatry University of San Diego San Diego California USA.
Alastair J H BrownHeptares Therapeutics Ltd Cambridge UK.
Malcolm Peter WeirHeptares Therapeutics Ltd Cambridge UK.
Miles CongreveHeptares Therapeutics Ltd Cambridge UK.
Tim TaskerHeptares Therapeutics Ltd Cambridge UK.
Heptares Therapeutics (United Kingdom) · GBBridge Pharma (United States) · USKowa (United Kingdom) · GBUniversity of Cambridge · GBUniversity of New Haven · USUniversity of San Diego · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThis study examined the safety and pharmacodynamic effects of selective muscarinic M

methodsA randomized, double-blind, placebo-controlled 4-week safety study of HTL0018318 with up-titration and maintenance phases, observing exploratory effects on electrophysiological biomarkers and cognition.

resultsTreatment-emergent adverse events (TEAEs) were mild and less frequently reported during maintenance versus titration. Headache was most commonly reported (7-21%); 0 to 13% reported cholinergic TEAEs (abdominal pain, diarrhea, fatigue, nausea) and two patients discontinued due to TEAEs. At 1 to 2 hours post-dose, HTL0018318-related mean maximum elevations in systolic and diastolic blood pressure of 5 to 10 mmHg above placebo were observed during up-titration but not maintenance. Postive effects of HTL0018318 were found on specific attention and memory endpoints. DISCUSSION: HTL0018318 was well tolerated in mild-to-moderate AD patients and showed positive effects on attention and episodic memory on top of therapeutic doses of donepezil.

Indexed as

Alzheimer's diseaseattentioncholinergicclinical trialcognitionCogstate neuropsychological test batteryelectrophysiologyevent related potentialHTL0018318memorymuscarinic M1 receptorpharmacodynamicsafetysymptomatictolerability

Identifiers

PMID35229025
PMCPMC8864442
OpenAlexW4214502830

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.