Evidence mapPaperPMID 39356093Full record

Trial reportClinical and translational science2024

Safety, pharmacokinetics, and pharmacodynamics of ART-648, a PDE4 inhibitor in healthy subjects: A randomized, placebo-controlled phase I study.

Akira Tanaka, Hiroshi Nagabukuro, Kanako Kuniyeda, Haruhi Ando, Toshinori Higashi, Hirokazu Wakuda, Naoyuki Otani, Hideo Kudo, Masae Kuranari, Hidetoshi Furuie and 1 more

Abstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in Clinical and translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
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

2 citing papers in PubMed.

  1. Trial
  2. 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

11 authors.

Akira TanakaDepartment of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.ORCID 0009-0008-9821-3325
Hiroshi NagabukuroDepartment of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.
Kanako KuniyedaDepartment of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.ORCID 0000-0002-4466-0145
Haruhi AndoDepartment of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.ORCID 0000-0002-6183-2674
Toshinori HigashiCTD Inc., Tokyo, Japan.
Hirokazu WakudaDepartment of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.ORCID 0000-0002-5717-8251
Naoyuki OtaniDepartment of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.ORCID 0000-0002-0127-2118
Hideo KudoDepartment of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.ORCID 0000-0001-8920-1447
Masae KuranariDepartment of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.
Hidetoshi FuruieMedical Corporation Heishinkai OPHAC Hospital, Osaka, Japan.ORCID 0000-0002-8256-0516
Naoto UemuraDepartment of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.ORCID 0000-0002-3722-8979

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Phosphodiesterase 4 (PDE4) inhibitor is associated with a broad-spectrum anti-inflammatory mechanism. However, securing clinically efficacious doses with sufficient safety margins remains challenging due to class specific adverse events that are often unavoidable in the clinic. ART-648 is an orally available PDE4 inhibitor being developed for the treatment of inflammatory diseases. According to the estimated clinical doses based on an in vitro whole-blood assay, a phase I study was designed. The purpose of this phase I study was to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) following single and multiple administration of ART-648 in healthy subjects. PD was assessed by suppression of lipopolysaccharide-induced TNFα release in ex vivo whole-blood assay. In the single rising dose study, ART-648 was safe and well tolerated with a dose-proportional increase in exposures up to 4 mg. Single doses of ART-648 demonstrated dose-dependent PD response, indicating target engagement at 2-8 mg doses. In the multiple rising dose study, doses up to 4 mg BID after careful titration were well tolerated, while doses up to 6 mg BID were tolerated not in all but the majority of subjects. In conclusion, ART-648 exhibits a favorable PK profile with robust target engagement at clinically safe and tolerated doses identified in healthy subjects.

Indexed as

Dose-Response Relationship, DrugHealthy VolunteersPhosphodiesterase 4 InhibitorsAdministration, OralAdultDouble-Blind MethodFemaleHumansLipopolysaccharidesMaleMiddle Agedpara-AminobenzoatesSulfonamidesTumor Necrosis Factor-alphaYoung AdultLipopolysaccharidespara-AminobenzoatesPhosphodiesterase 4 InhibitorsSulfonamidestanimilastTumor Necrosis Factor-alpha

Identifiers

PMID39356093
PMCPMC11445709

What Socratic 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 Socratic graph.