Evotec’s EVT 101 Well Tolerated in Four Week Higher Repeat Dose Safety Study
News Jul 04, 2008
Evotec AG has announced top-line results of a double-blind, 4-week Phase Ib study with EVT 101, an orally active NR2B-subtype selective antagonist of NMDA receptors with potential in Alzheimer’s disease, neuropathic pain and other indications. The study showed in both young and elderly subjects that the drug was well tolerated up to the highest dose tested.
The study was designed to evaluate safety/tolerability, pharmacokinetics, and pharmacodynamics during prolonged dosing with EVT 101 as com-pared to placebo, but at higher dose levels and for a longer duration that the previously completed Phase I study. The study was conducted and completed as planned per protocol.
EVT 101 was administered to 48 young and elderly healthy subjects over four weeks. Up to the highest dose level (12 mg/day in elderly, 15 mg/day in young subjects) EVT 101 was well tolerated by both populations. No severe or serious adverse events were reported, and only few transient, mostly mild, adverse events occurred.
This safety and tolerability profile is extremely encouraging as the doses evaluated are predicted to be well into the anticipated therapeutic range. As previously reported (see press re-lease, March 28, 2008), this trial contained a sub-study in which drug CSF levels were measured to determine the extent of brain penetration.
Psychometric tests, examining different aspects of cognitive function, revealed a mixed pattern of minor transient changes, as expected from populations of healthy subjects performing optimally in cognitive tasks.
“Together with results from the fMRI brain imaging which we announced in March, these results provide a robust Phase Ib package. We have found doses of this highly specific compound that achieve a high level of brain exposure to achieve a high level of NR2B receptor blockade. These doses produce specific modulation of relevant brain areas and, importantly, are also well tolerated. This provides a good foundation for moving forward with the clinical development of this compound and enables us to investigate EVT 101 in relevant patient groups,” commented Dr Tim Tasker, Executive Vice President Clinical Development, Evotec AG.