Results and evaluation of a first-in-human study of RG7342, an mGlu5 positive allosteric modulator, utilizing Bayesian adaptive methods.

Single oral doses of RG7342 were generally tolerated up to 0.6 mg under fasting and 0.9 mg under fed conditions in healthy subjects. Bayesian adaptive methods describing the probability of DLEs were applied effectively to support dose escalation. MTDs (fasting, fed) were associated with a Cmax of 6.5 ng ml-1 . The development of RG7342 was discontinued owing to the potential challenges associated with a long half-life in context of the observed adverse events.