Evaluation of the Safety and Pharmacokinetics of MSI-195 to a Commercial S-Adenosylmethionine
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 1

Summary: 
      This study was a pharmacokinetic and safety evaluation of the S-adenosylmethionine
      formulation MSI-195, and a commercial comparator. The study was broken into two stages. The
      first stage was an exploratory single ascending dose design of MSI-195 in 8 healthy normal
      male volunteers. The second stage was a single dose evaluation, targeting 26 male and female
      volunteers at set doses of MSI-195 and commercial comparator in a cross-over design followed
      by a food effect study on MSI-195. Plasma samples were collected and assayed for
      S-adenosylmethionine. Pharmacokinetic parameters were calculated using that data.
    

Detailed description: 
      The study was focussed on the safety and pharmacokinetic evaluation of MSI-195; a novel
      patented formulation of S-adenosylmethionine. MSI-195 is a 400 mg dosage strength, tablet
      formulation comprising a core tablet, a seal coat and an enteric coat. The commercial
      comparator is SAM-e CompleteTM, manufactured by Pharmavite under the NatureMadeTM brand.

      This study consisting of two stages. The first stage was an exploratory single ascending dose
      design of MSI-195 in 8 healthy normal male volunteers. The second stage was a more
      comprehensive single dose evaluation, targeting 26 male and female volunteers at set doses of
      MSI-195 and commercial comparator in a cross-over design followed by a food effect study on
      MSI-195.

      Stage 1 design In each period of this stage of the study, ascending single doses of 400 mg,
      800 mg and 1600 mg of MSI-195 was orally administered under fasted conditions, followed by 24
      hours of blood draws at periodic intervals for the determination of plasma concentration of
      S-adenosylmethionine in a repeated-measure design. The drug administrations were separated by
      a wash-out of 7 calendar days.

      Stage 2 design In the first 2 periods of this stage of the study, a single 800 mg dose of
      MSI-195 and a single 1600 mg dose of commercial comparator were orally administered under
      fasted conditions, in a 2-way crossover design. During the 3rd period, a single 800 mg dose
      of MSI-195 was administered under fed conditions to all subjects. The drug administrations
      were separated by a wash-out of 7 calendar days. For each dosing, subjects had periodic blood
      draws over a 24 hour period to determine the plasma concentration of S-adenosylmethionine as
      a function of time.

      Male and female volunteers were included in the study. Subjects were in good health as
      determined by a medical history, complete physical examination (including vital signs),
      electrocardiogram (ECG), neurological examination and a panel of clinical laboratory tests.

      Blood samples were collected and stored frozen until assayed. The samples were assayed for
      S-adenosylmethionine using a validated HPLC method with MS/MS detection.

      For pharmacokinetic assessments, the main absorption and disposition parameters were
      calculated using a non-compartmental approach with a log-linear terminal phase assumption.
      The pharmacokinetic parameters of this trial were Cmax, Tmax, AUCT, AUC∞, AUCT/∞, Kel and
      T½el.

      The safety parameters assessed included the occurrence of adverse events, the measurement of
      clinical laboratory parameters, vital signs, neurological function tests, physical
      examination and ECG
    

Intervention name(s): Ademetionine
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Stage 1 - single ascending dose, Stage 2 - crossover and food effect study
Masking: None (Open Label)
Primary purpose: Other
Keywords: depression