Results From a Multiple Ascending Dose Study in Healthy Volunteers of ACD856, a Positive Modulator of Neurotrophin Trk‐Receptors

Abstract

AbstractBackgroundACD856 is a novel positive allosteric modulator of Trk‐receptors in clinical development for the treatment of Alzheimer’s disease and other disorders where cognition is impaired. The aim of this study was to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple ascending doses of ACD856.Method24 healthy volunteer subjects were administered ACD856 or placebo as a daily oral solution over 7 days in 3 cohorts of stepwise ascending doses. After each dose, the safety, tolerability, and pharmacokinetics of ACD856 were assessed by an internal Safety Review Committee to decide on the escalation of dose to the next cohort.ResultThere were no clinically significant changes from baseline in mean ECG, vital signs, physical examination findings, clinical chemistry, haematology, coagulation, or urinalysis parameters after receiving the 7 daily doses of ACD856. Occasional individual abnormal laboratory values were observed but all were assessed as not clinically significant. Most of the reported adverse events were of mild intensity, only a few were of moderate intensity and none of severe intensity. No serious adverse events were reported.The pharmacokinetic data confirmed the findings from the previously performed single ascending dose (SAD) study, including that ACD856 has a rapid absorption, long half‐life, high bioavailability, and a linear dose‐dependent exposure. The Cmax at steady state was approximately 1.6‐fold higher than the initial dose administration and no time‐dependent clearance was observed. Moreover, initial CSF data confirms CNS exposure of ACD856. Further PK, CSF and pharmacodynamic data will be shown at the time of presentation.ConclusionACD856 was shown to be safe and well tolerated in man at the tested dose levels and with a suitable pharmacokinetic profile for further clinical development. In the next step, ACD856 will be evaluated in a phase Ib study with the aim to further assess pharmacodynamic effects.