Dataset Information

A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug.

ABSTRACT:

Background and purpose

ATB-346 is a hydrogen sulfide (H₂ S)-releasing anti-inflammatory and analgesic drug. Animal studies demonstrated negligible gastrointestinal (GI) damage despite marked inhibition of COX activity and significant analgesic and anti-inflammatory effects. In humans, ATB-346 (250 mg once daily) was found to inhibit COX to the same extent as naproxen (550 mg twice daily).

Experimental approach

Two hundred forty-four healthy volunteers completed a 2-week, double-blind study, taking either ATB-346 (250 mg once daily) or naproxen (550 mg twice daily), with upper GI ulceration being examined endoscopically.

Key results

Forty-two per cent of the subjects taking naproxen developed at least one ulcer (?3-mm diameter), while only 3% of the subjects taking ATB-346 developed at least one ulcer. The two drugs produced comparable and substantial (>94%) suppression of COX activity. Subjects in the naproxen group developed more ulcers per subject than ATB-346-treated subjects and a greater incidence of larger ulcers (?5-mm diameter). The incidence of dyspepsia, abdominal pain, gastro-oesophageal reflux, and nausea was lower with ATB-346 than with naproxen. Subjects treated with ATB-346 had significantly higher plasma levels of H₂ S than those treated with naproxen.

Conclusions and implications

This Phase 2B study provides unequivocal evidence for a marked reduction of GI toxicity of the H₂ S-releasing analgesic/anti-inflammatory drug, ATB-346, as compared to the conventional dose of naproxen that produced equivalent suppression of COX.

Linked articles

This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.

SUBMITTER: Wallace JL

PROVIDER: S-EPMC7024706 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug.

Wallace John L JL Nagy Peter P Feener Troy D TD Allain Thibault T Ditrói Tamás T Vaughan David J DJ Muscara Marcelo N MN de Nucci Gilberto G Buret Andre G AG

British journal of pharmacology 20190411 4

<h4>Background and purpose</h4>ATB-346 is a hydrogen sulfide (H<sub>2</sub> S)-releasing anti-inflammatory and analgesic drug. Animal studies demonstrated negligible gastrointestinal (GI) damage despite marked inhibition of COX activity and significant analgesic and anti-inflammatory effects. In humans, ATB-346 (250 mg once daily) was found to inhibit COX to the same extent as naproxen (550 mg twice daily).<h4>Experimental approach</h4>Two hundred forty-four healthy volunteers completed a 2-week ...[more]

PMID: 30834513

Similar Datasets

Project description:By electrospinning of polycaprolactone (PCL) solutions containing N-(benzoylthio)benzamide (NSHD1), a H2S donor, fibrous scaffolds with hydrogen sulfide (H2S) releasing capability (H2S-fibers) are fabricated. The resultant microfibers are capable of releasing H2S upon immersion in aqueous solution containing biological thiols under physiological conditions. The H2S release peaks of H2S-fibers appeared at 2-4h, while the peak of donor alone showed at 45 min. H2S release half-lives of H2S-fibers were 10-20 times longer than that of donor alone. Furthermore, H2S-fibers can protect cells from H2O2 induced oxidative damage by significantly decreasing the production of intracellular reactive oxygen species (ROS). Finally, we investigated the H2S-fibers application as a wound dressing in vitro. Given that H2S has a broad range of physiological functions, H2S-fibers hold great potential for various biomedical applications.Hydrogen sulfide, as a gaseous messenger, plays a crucial role in many physiological and pathological conditions. Recent studies about functions of H2S suggests H2S-based therapy could be promising therapeutic strategy for many diseases, such as cardiovascular disease, arthritis, and inflammatory bowel disease. Although many H2S donors have been developed and applied for biomedical studies, most of H2S donors have the shortage that the H2S release is either too fast or uncontrollable, which poorly mimic the biological generation of H2S. By simply combining electrospinning technique with our designed biological thiols activated H2S donor, NSHD1, we fabricated H2S releasing microfibers (H2S-fibers). This H2S-fibers significantly prolonged the releasing time compared to H2S donor alone. By adjusting the electrospinning parameters, tunable releasing profiles can be achieved. Moreover, the H2S fibers can protect cardiac myoblasts H9c2 and fibroblast NIH 3T3 from oxidative damage and support their proliferation as cellular scaffolds. To our knowledge, this is the first report of electrospun fibers with H2S releasing capacity. We anticipate this H2S-releasing scaffold will have great potential for biomedical applications.

Dataset Information

A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Linked articles

Publications

A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets