Evidence map›Paper›PMID 32067249›Full record

Trial reportBritish journal of clinical pharmacology2020

Pharmacokinetics, pharmacodynamics and safety of the inverse retinoic acid-related orphan receptor γ agonist AZD0284.

Sara Asimus, Robert Palmér, Muna Albayaty, Henrik Forsman, Christina Lundin, Marita Olsson, Rikard Pehrson, John Mo, Muir Russell, Sara Carlert and 2 more

Open access · bronzeAbstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

5 citing papers in PubMed, 17 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
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

12 authors at 6 institutions in 8 countries.

Sara AsimusClinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca Gaithersburg, MD, USA.ORCID 0000-0001-9339-0615
Robert PalmérClinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca Gothenburg, Sweden.
Muna AlbayatyEarly Phase Clinical Unit, Parexel, London, UK.
Henrik ForsmanClinical Development, Research and Early Development, Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Christina LundinClinical Development, Research and Early Development, Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Marita OlssonEarly Biostats and Statistical Innovation, Data Science and AI, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Rikard PehrsonResearch and Early Development, Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
John MoPatient Safety, Respiratory, Inflammation and Autoimmunity, Chief Medical Office, R&D, AstraZeneca, Gothenburg, Sweden.
Muir RussellStudy Delivery, Early Oncology Clinical, Oncology R&D, AstraZeneca, Cambridge, UK.
Sara CarlertEarly Product Development, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
David CloseClinical Development, Research and Early Development, Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
David KeelingResearch and Early Development, Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
AstraZeneca (Finland) · FIAstraZeneca (United Kingdom) · GBAstraZeneca (Italy) · ITAstraZeneca (Netherlands) · NLAstraZeneca (Poland) · PLPAREXEL International (United Kingdom) · GB

Funding

AstraZeneca
6 · The paper itself

Abstract

aimsRetinoic acid-related orphan receptor γ (RORγ), a master regulator of T-helper 17 (Th17) cell function and differentiation, is an attractive target for treatment of Th17-driven diseases. This first-in-human study aimed to investigate the pharmacokinetics, pharmacodynamics, safety and tolerability of the inverse RORγ agonist AZD0284.

methodsWe conducted a phase I, randomized, single-blind, placebo-controlled, two-part, first-in-human study with healthy subjects receiving single (4-238 mg) or multiple (12-100 mg) oral doses of AZD0284 or placebo after overnight fasting. Subjects in the one single dose cohort additionally received a single dose of AZD0284 after a high-calorie meal. AZD0284 plasma concentrations, as well as inhibition of ex vivo-stimulated interleukin (IL)-17A release in whole blood, were frequently measured after both single and multiple dosing.

resultsEighty-three men participated in the study. AZD0284 was absorbed rapidly into plasma after oral dosing and exhibited a terminal half-life of 13-16 hours. Both the area under the concentration-time curve (AUC) and maximum concentration (C

conclusionsAZD0284 was well tolerated, rapidly and dose-dependently absorbed, and reduced stimulated IL-17A release after single and multiple dosing. The results of this study support further clinical development of AZD0284.

Indexed as

TretinoinAdministration, OralArea Under CurveDose-Response Relationship, DrugDouble-Blind MethodHalf-LifeHumansMaleSingle-Blind MethodTretinoinautoimmune diseasephase I clinical trialpsoriasisRORγTh17 cells

Identifiers

PMID32067249
PMCPMC7319014
OpenAlexW3006690226

What OpenQuestion holds

Textmetadata
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.