Endoscopic comparison of gastroduodenal injury with over-the-counter doses of new fast-dissolving ibuprofen and paracetamol formulations: a randomized, placebo-controlled, 4-way crossover clinical trial

Endoscopic comparison of gastroduodenal injury with over-the-counter doses of new fast-dissolving ibuprofen and paracetamol formulations: a randomized, placebo-controlled, 4-way crossover clinical trial

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Frank L Lanza,1 Agron Collaku,2 Dongzhou J Liu3 1Department of Gastroenterology, Houston Institute for Clinical Research, Houston, TX, USA; 2Biostatistics Department, GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA; 3Global Clinical Development, GlaxoSmithKline, Collegeville, PA, USA Background: While gastrointestinal (GI) effects of standard ibuprofen and N-acetyl-p-­aminophenol (APAP) have been reported, upper GI injury following treatment with fast-dissolving (FD) formulations of these analgesics has not been investigated.We evaluated upper GI effects of over-the-counter doses of 2 FD ibuprofen products and 1 FD-APAP product.Methods: In a randomized, placebo-controlled, endoscopist-blinded, 4-way crossover study, 28 healthy subjects received FD ibuprofen 2×200 mg liquid capsules 3 times daily (TID), ibuprofen 2×200 mg tablets TID, FD-APAP 2×500 mg tablets 4 times daily (QID), and placebo 2×500 mg tablets QID for 7 days.The primary end point was gastric mucosal damage assessed by endoscopy using the Lanza scale: 0=normal stomach or proximal duodenum, 1=mucosal hemorrhages only, catherine lansfield ombre rainbow clouds eyelet curtains 2=1 or 2 erosions, 3=numerous (3–10) erosions, and 4=large number of erosions (>10) or ulcer.Secondary end points included duodenal mucosal damage (Lanza scale); gastroduodenal mucosal injury, classified as present (gastric and/or duodenal endoscopy score ≥2) or absent (gastric and/or duodenal endoscopy biomat for sale score <2); and number of hemorrhages, erosions, and ulcers counted separately in the stomach and duodenum.

Results: Significantly greater gastric mucosal injury was observed after treatment with both ibuprofen products vs FD-APAP (p<0.0001 and p=0.0095, respectively).FD-APAP showed no difference from placebo (p=0.4794).

The odds of having an incidence of gastroduodenal mucosal injury were over 6 times greater from FD ibuprofen liquid capsule treatment (odds ratio [OR]=6.19, 95% confidence interval [CI]: 1.60, 23.97) and over 3 times greater from ibuprofen tablet treatment (OR=3.19, 95% CI: 0.

8, 12.74) vs FD-APAP.Conclusion: Treatment with 2 ibuprofen products was associated with significant gastric mucosal injury.Of the 4 treatments studied, FD ibuprofen liquid capsules had the highest risk of incidence of gastroduodenal mucosal injury.Treatment with FD-APAP did not induce any clinically or statistically significant gastroduodenal mucosal injury.

Keywords: gastric mucosal damage, APAP, NSAIDs, erosions, hemorrhages, ulcer.