Clinical Studies with Phospholipid-Associated NSAIDs

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DESCRIPTION (adapted from the application) The major objective of the proposed clinical trial will be to evaluate the gastroduodenal toxicity and biological activity of a formulation of aspirin (ASA) and another non-steroidal anti-inflammatory drug (NSAID), diclofenac, chemically associated with the zwitterionic phospholipid, phosphatidylcholine (PC). This will be accomplished first, by comparing the effects of unmodified ASA (administered at a dose of 650 mg, t.i.d.) to that of the ASA-PC test compound, over a one month study period, in healthy human subjects with no history of gastrointestinal or inflammatory disease and who are not frequent NSAID users. The subjects will initially receive either the ASA or the ASA-PC based upon a randomized program, and after a washout period of no less than 6 weeks will enter the second arm of the study where they will receive the alternate medication. Endoscopic procedures will be performed by the professional staff, who are blinded to which test-drug the subject is taking, at the beginning (baseline) and end (follow-up) of the study period, at which time the number, size and location of gastroduodenal ulcers/erosions will be scored under video-endoscopy, biopsies will be taken for surface hydrophobicity (contact angle analysis), cyclo-oxygenase (COX) activity (radioimmunoassay/RIA) and blood collected for assessment of platelet aggregability, thromboxane (TXB2) conc. and hematocrit. A second study will be designed in a similar manner to the above, to compare the gastroduodenal toxicity and biological activity of diclofenac (75 mg b.i.d.) with diclofenac-PC, except in this case we will add a third arm of the study in which the subjects are administered the COX- inhibitor, Celecoxib, at a dose (200 mg b.i.d.) having equivalent therapeutic efficacy to diclofenac.