Several conditions require treatment with alkalinising agents. The objective is to restore the homeostasis on various parameters or stabilise some urine parameters. The agents used currently have to be administered several times a day in order to maintain the effect but have a bad gastro-intestinal tolerability, both leading to bad compliance. A new formulation in the form of granules (ADV7103) has been developed to limit the administration to 2 intakes daily and improve gastro-intestinal tolerability.

A randomized, placebo-controlled, double-blind, two-period cross-over study has been conducted to evaluate the pharmacodynamics, safety and tolerability of repeated oral doses of ADV7103 at three dose levels, in 8 subjects. The effect was evaluated on urine pH on the first morning urines and on 12 fresh urine collections of 2hours for 24hours, after 4 and 5 days of treatment. The safety and tolerability was evaluated.

Urine pH increased proportionally to the dose administered (Fig. 1). All doses administered demonstrated a statistically significant increase of urine pH as compared to placebo (P<0.05 or P<0.0001). No saturating effect occurred within the dose-range tested. A single gastro-intestinal adverse event was reported for 240 administrations: an episode of nausea of mild intensity, 30minutes after the high dose intake. Very few urine samples were noted above pH8.

A stable urine pH over 24hours with two doses per day was obtained for the majority of samples, despite a strong nyctohemeral rhythm.

ADV7103, proved its efficacy in maintaining a constant increase of the urine pH over 24hours with 2 daily intakes. The safety profile has been confirmed.