Pharmacokinetic study of a novel oral formulation of S-adenosylmethionine (MSI-195) in healthy subjects: dose escalation, food effect and comparison to a commercial nutritional supplement product.

Background: A novel, high bioavailability oral, enteric coated tablet formulation of S-adenosylmethionine (MSI-195) has been developed for life science application. The present research reports on a Phase 1 study to (i) determine the safety of single doses of MSI-195 (ii) to determine the dose proportionality of MSI-195 at doses of 400, 800 and 1600 mg (iii) determine the pharmacokinetics of MSI-195 compared with a commercial reference product (SAM-e Complete™) over 24 h and (iv) to determine the effect of food on the pharmacokinetic profile of MSI-195 in human subjects.

Methods: This study was a pharmacokinetic and safety evaluation of MSI-195 and a commercial comparator broken into two stages.

Early score fluctuation and placebo response in a study of major depressive disorder.

Early score fluctuation in double-blind, placebo-controlled studies may affect the reliability of the baseline measurement and adversely affect the eventual study outcome. We examined the effect of early score fluctuation during a 2-week double-blind placebo lead-in period in a phase II, double-blind, placebo-controlled trial of adjunctive s-adenosyl methionine (MSI-195) in MDD subjects who had had an inadequate response to ongoing antidepressant treatment. The overall study failed to meet its specified endpoints.

An augmentation study of MSI-195 (S-adenosylmethionine) in Major Depressive Disorder.

We conducted a 6-week double-blind, placebo-controlled, augmentation study comparing the efficacy and safety of MSI-195 800 mg (a proprietary formulation of S-adenosylmethionine) or placebo added to ongoing antidepressant medication (ADT) in acutely depressed subjects with Major Depressive Disorder (MDD) who had experienced an inadequate response to their ongoing ADT (The Horizon Study, ClinicalTrials.gov NCT01912196). There were 234 eligible subjects randomized to either MSI-195 (n = 118) or placebo (n = 116).