Clinical Development

An enhanced Phase Ia single ascending dose clinical trial addressed safety, tolerability, and pharmacokinetics of intranasal Memogain in healthy young and elderly subjects, in comparison to the daily recommended doses of the reference drugs Reminyl (16mg) and Aricept (10mg). The healthy young and elderly subjects in the study were also tested for drug-dependent improvements in cognition.

Administration of Memogain was safe and well tolerated at all dose levels investigated. All adverse events (AE) were either mild or moderate. Nausea was elevated in a few subjects after administration of oral Reminyl 16 mg and Memogain 44 mg, but not at the lower dose levels of Memogain. These excellent safety data will allow an efficacious dose to be administered from the first day of treatment, thus avoiding the months-long up-titration periods usually required by oral galantamine (Reminyl), and the other drugs of its class, to allow patients time to sufficiently tolerate such AEs as nausea, vomiting and diarrhea. Enhanced tolerability of Memogain is likely to improve patients’ compliance at all stages of treatment – current estimates of drop–out rates range from 30-50% due to lack of perceived benefit and continuing GI side effects.  Memogain has the potential of regaining the lost market revenue from these drop-outs.

Memogain enhances by more than one order of magnitude the active concentration of galantamine in the brain, compared to orally administered galantamine. The kinetics of Memogain’s exposure in plasma are consistent with the concept of being preferentially and rapidly distributed into the brain where the pro-drug is enzymatically cleaved to the active drug galantamine. The pharmacokinetics profile of Memogain suggests that once a day dosing will be possible.

The cognitive test battery employed in the phase Ia trial demonstrated effects of Memogain on several important cognition domains. Particularly noteworthy were improved performance in the adaptive tracking test (measuring eye-hand coordination, vigilance and arousal) in both young and elderly subjects at different dose levels, and in the visual verbal learning test (VVLT, measuring word learning and recall) in healthy elderly at 22 mg and higher dose levels, suggestive of improved short-term memory capacity.  Neither oral administration of Aricept nor of galantamine (Reminyl) showed such effect on the VVLT.

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