Add-On Study of MSI-195 (S-Adenosyl-L-Methionine, SAMe) for Patients With Major Depressive Disorder (MDD)

A Double-Blind, Placebo-Controlled, Randomized Add-On Study of MSI-195 (Methylation Sciences Inc. S-Adenosyl-L-Methionine, SAMe) For Patients With Major Depressive Disorder(MDD) Who Have Had An Inadequate Response to Current Antidepressant Therapy

The purpose of this study is to determine the efficacy and safety of 800 mg MSI-195 in reducing symptoms of depression in Major Depressive Disorder (MDD)patients with inadequate response to current antidepressant therapy.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder (MDD)
• Intervention / Treatment: Drug: Placebo; Drug: MSI-195

• Study Type: Interventional
• Enrollment (Actual): 376
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • MSI Investigational Site
  • California
    • Encino, California, United States, 91316
      • MSI Investigational Site
    • Escondido, California, United States, 92025
      • MSI Investigational Site
    • Garden Grove, California, United States, 92845
      • MSI Investigational Site
    • Los Alamitos, California, United States, 90720
      • MSI Investigational Site
    • Los Angeles, California, United States, 90024
      • MSI Investigational Site
    • National City, California, United States, 91950
      • MSI Investigational Site
    • Newport Beach, California, United States, 92660
      • MSI Investigational Site
    • Oakland, California, United States, 94612
      • MSI Investigational Site
    • Oceanside, California, United States, 92056
      • MSI Investigational Site
    • Torrance, California, United States, 90502
      • MSI Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32256
      • MSI Investigational Site
    • Kissimmee, Florida, United States, 34741
      • MSI Investigational Site
    • Lauderhill, Florida, United States, 33319
      • MSI Investigational Site
    • Orlando, Florida, United States, 32806
      • MSI Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • MSI Investigational Site
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • MSI Investigational Site
  • Maryland
    • Towson, Maryland, United States, 21285
      • MSI Investigational Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • MSI Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • MSI Investigational Site
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • MSI Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • MSI Investigational Site
  • New York
    • New York, New York, United States, 10128
      • MSI Investigational Site
    • Rochester, New York, United States, 14618
      • MSI Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • MSI Investigational Site
    • Dayton, Ohio, United States, 45417
      • MSI Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97210
      • MSI Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • MSI Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • MSI Investigational Site
    • Austin, Texas, United States, 78754
      • MSI Investigational Site
    • Dallas, Texas, United States, 75231
      • MSI Investigational Site
    • Houston, Texas, United States, 77008
      • MSI Investigational Site
    • Houston, Texas, United States, 77098
      • MSI Investigational Site
  • Utah
    • Murray, Utah, United States, 84123
      • MSI Investigational Site
  • Washington
    • Bellevue, Washington, United States, 98007
      • MSI Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meets the Diagnostic and Statistical Manual of Mental Disorder, 4th Edition, Text Revision (DSM-IV-TR) criteria for Major Depressive Disorder (MDD)
• A total score of 16 or higher on the Hamilton Rating Scale for Depression- 17 item version (HAM-D17) at the Screening and Baseline Visits, with a score of ≥2 on mood item 1.
• Have experienced 1-4 prior Major Depressive Episodes. Patients with more than 5 lifetime episodes (including current episode) will require discussion with the medical monitor prior to inclusion.
• Failed 1-3 treatment regimens in the current depressive episode
• Received an adequate dose and duration of Antidepressant Therapy (ADT) (on ADT for at least 6 weeks with a stable dose for at least 3 weeks)

Exclusion Criteria:

• Failed 4 or more adequate treatment regimens in current episode of depression
• patient may have a significant risk for suicidal behavior during the course of their participation in the study
• Intolerance to SAMe; Prior use of MSI-195
• History of any of the following psychiatric disorders: eating disorder within 6 months; obsessive compulsive disorder, psychotic disorder, bipolar disorder, mental retardation, dementia or other forms of cognitive impairment at any time or alcohol or substance abuse
• >3X upper limit of normal (ULN) Alkaline Phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT); >1.5X ULN total bilirubin
• Pregnant or lactating women
• Any history of seizures, excluding febrile seizures
• Known positivity for human immunodeficiency virus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSI-195; Patients randomized to the MSI-195 arm will receive treatment with 2 tablets (800 mg) of MSI-195 plus on-going antidepressant therapy (ADT). MSI-195 800 mg (two tablets) taken orally once a day in the morning on an empty stomach with water (food should be avoided for at least 1 hr after taking the study drug)	Drug: MSI-195
Placebo Comparator: Placebo; Patients randomized to the placebo arm will receive 2 tablets placebo plus on-going antidepressant therapy (ADT). Placebo (two tablets) taken orally once a day in the morning on an empty stomach with water (food should be avoided for at least 1 hr after taking the study drug).	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the total Hamilton Depression Rating Scale (HAM-D17) between randomization and end of study.	Based on historical data, the standard deviation is assumed to range between 9 and 12. With a standard effect size of 0.367 a total of at least 120 evaluable patients per group are needed to provide 80% power with a two-sided 5% significance level. HAM-D17 will be derived from the Combined HAM-D28-MADRS Instrument.	assessed from baseline to week 8 (end of study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in the total score of the Montgomery-Asberg Depression Rating Scale (MADRS)	for the MADRS, the number and proportion of patients who are responders at the end of the study and the number and proportion of patients who are in remission at the end of the study will be summarized by treatment group, along with the difference and 95% confidence interval for the difference (based on the Wilson Score method).	collected at baseline, weeks 2, 4, 6, 7 and 8 (end of study)
change in total score of the Clinical Global Impression Improvement Scale (CGI-S)	the number and proportion of patients who are responders at the end of the study and the number and proportion of patients who are in remission at the end of the study will be summarized by treatment group, along with the difference and 95% confidence interval for the difference (based on the Wilson Score method). Remission is defined as a score of 1 or 2.	assessed from baseline, weeks 2, 4, 7 and 8 (end of study)
change from randomization to each study visit in the total score of the Inventory of Depressive Symptomatology-Self Rated (IDS-SR30)	A response is defined as a reduction in the IDS-SR30 score of ≥50% and remission is defined as a score of ≤14.	assessed on baseline visit, Week 2, 4, 6, and 8 (end of study).
Adverse events	collected from signing informed consent through 7 days after the last dose of study treatment. Ascertained by qualified clinician.	collected at baseline, weeks 1, 2, 3, 4, 6, 8 and 9 (follow up)
Columbia Suicide Severity Rating Scale (C-SSRS)	administered by qualified clinician	assessed at baseline, weeks 2, 4, 6 and 8 (end of study)

Collaborators and Investigators

• Sponsor: MSI Methylation Sciences, Inc.

Publications and helpful links

General Publications

• Targum SD, Cameron BR, Ferreira L, MacDonald ID. An augmentation study of MSI-195 (S-adenosylmethionine) in Major Depressive Disorder. J Psychiatr Res. 2018 Dec;107:86-96. doi: 10.1016/j.jpsychires.2018.10.010. Epub 2018 Oct 18.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: July 26, 2013
• First Submitted That Met QC Criteria: July 30, 2013
• First Posted (Estimate): July 31, 2013

Study Record Updates

• Last Update Posted (Estimate): March 18, 2016
• Last Update Submitted That Met QC Criteria: March 17, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Depressive Disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major
• Other Study ID Numbers: MSI-CP.002