Clinical trial: endoscopic evaluation of naproxen etemesil, a naproxen prodrug, vs. naproxen - a proof-of-concept, randomized, double-blind, active-comparator study.
BACKGROUND
Nonsteroidal anti-inflammatory drugs are associated with upper gastrointestinal mucosal injury. Naproxen etemesil is a lipophilic, non-acidic, inactive prodrug of naproxen that is hydrolysed to pharmacologically active naproxen once absorbed. We hypothesized that with lesser topical exposure to naproxen from the prodrug, there would be reduced gastroduodenal mucosal injury compared with naproxen.


OBJECTIVE
To compare the degree of endoscopic mucosal damage of naproxen etemesil vs. naproxen.


METHODS
This multicentre, randomized, double-blind, double-dummy trial compared oral naproxen etemesil 1200 mg twice daily (n = 61) with naproxen 500 mg twice daily (n = 59) for 7.5 days in 120 healthy subjects (45-70 years; mean 51 years; 58% female) with baseline total modified gastroduodenal Lanza score ≤ 2 (no erosions/ulcers) on endoscopy. The primary endpoint was mean total modified gastroduodenal Lanza score on day 7. A secondary endpoint was incidence of gastric ulcers.


RESULTS
The day 7 mean total modified gastroduodenal Lanza score was 2.8 ± 1.7 for naproxen etemesil vs. 3.5 ± 2.0 for naproxen (P = 0.03), and significantly fewer naproxen etemesil-treated subjects (3.3%) developed gastric ulcers compared with naproxen-treated subjects (15.8%) (P = 0.02).


CONCLUSIONS
In this first proof-of-concept study, naproxen etemesil was associated with significantly lower gastroduodenal mucosal injury compared with naproxen after 7 days of exposure (


BACKGROUND
NCT00750243).
Goldstein
J L
JL
Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA. jlgoldst@uic.edu
Jungwirthová
A
A
David
J
J
Spindel
E
E
Bouchner
L
L
Pešek
F
F
Searle
S
S
Skopek
J
J
Grim
J
J
Ulč
I
I
Sewell
K L
KL
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004311:Double-Blind Method; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects*; D011355:Prodrugs / Q000009:adverse effects*; D013276:Stomach Ulcer / Q000139:chemically induced*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D009288:Naproxen