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Type: Artigo
Title: A proof‐of‐concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide‐releasing anti‐inflammatory drug
Author: Wallace, John L.
Nagy, Peter
Feener, Troy D.
Allain, Thibault
Ditrói, Tamás
Vaughan, David J.
Muscara, Marcelo N.
Nucci, Gilberto de
Buret, Andre G.
Abstract: ATB‐346 is a hydrogen sulfide (H2S)‐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). 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. 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 H2S than those treated with naproxen. This Phase 2B study provides unequivocal evidence for a marked reduction of GI toxicity of the H2S‐releasing analgesic/anti‐inflammatory drug, ATB‐346, as compared to the conventional dose of naproxen that produced equivalent suppression of COX
Subject: Conteúdo gastrointestinal
Sulfeto de hidrogênio
Country: Reino Unido
Editor: John Wiley & Sons
Rights: Fechado
Identifier DOI: 10.1111/bph.14641
Date Issue: 2020
Appears in Collections:FCM - Artigos e Outros Documentos

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