Merrion Pharmaceuticals Ltd, (DUBLIN, Ireland and WILMINGTON, North Carolina), a privately-held international specialty pharmaceutical company engaged in the development of improved oral dosage forms of drugs that have poor bioavailability, announced the successful completion of a phase II clinical pharmacology study of MER 103. The new agent is an enteric-coated tablet of the bisphosphonate alendronate sodium (FosamaxR, Merck) in a GIPETâ„¢ (Gastrointestinal Permeation Enhancement Technology) formulation, Merrion's proprietary platform technology, which increases drug absorption. The patented MER 103 formulation features GIPET enhancers to substantially improve bioavailability and enteric coating to release the drug in the small intestine. These improvements may allow simplification of the current complex dosing regimen, avoid GI side effects, significantly reduce the dose, and potentially reduce the frequency of administration alendronate.

The phase II single dose, four-way crossover study was conducted in 16 postmenopausal women to evaluate the relative bioavailability of MER 103, under several fed or fasted conditions. An oral dose of Fosamax, was the reference drug, taken as per label. Based on urinary excretion data for alendronate, MER 103 gave an increase in relative bioavailability of approximately 15-fold when dosed at night time, 12-fold when dosed fasted overnight, and 3-fold when dosed with a high-fat breakfast.

The study compared the absorption of a 6 mg dose of MER 103 administered under three different conditions: in the fasted state, with a high-fat meal, and at bedtime, against a 35 mg dose of Fosamax administered in the fasted state as per label directions. Subjects who received 6 mg MER 103 after an overnight fast absorbed approximately twelve times more alendronate on a dose adjusted basis than when they received 35 mg of Fosamax under the same conditions. In practice, these data indicate that a 6 mg weekly dose of MER 103 will be bioequivalent to a 70 mg weekly dose of Fosamax.

Subjects who received MER 103 at bedtime, approximately 4 hours after the evening meal, absorbed the same amount of alendronate as they did when taking the drug after an overnight fast. Subjects were instructed to lie down for at least 2 hours after taking their medication rather than remaining upright per the dosing instructions for the marketed oral bisphosphonates. There were no serious or clinically significant adverse events in this treatment group. The study also showed that, as with all bisphosphonate drugs, coadministration with food reduced the absorption of MER 103, although the percentage of drug absorbed was still greater than for the Fosamax dose.

The company believes that the combination of improved bioavailability and the elimination of the morning dosing ritual addresses directly two of the major limitations of oral bisphosphonates. Up to 60% of patients taking weekly bisphosphonates discontinue therapy within the first year, primarily because of difficulty in complying with the morning dosing ritual.

—A. Techman

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