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

• Sponsor: MSI Methylation Sciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01912196
• Collaborator: (none)
• Enrollment: 376
• Locations: 35
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder (MDD)	Drug: MSI-195; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 376 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in the total Hamilton Depression Rating Scale (HAM-D17) between randomization and end of study. [assessed from baseline to week 8 (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.

Secondary Outcome Measures

1. change in the total score of the Montgomery-Asberg Depression Rating Scale (MADRS) [collected at baseline, weeks 2, 4, 6, 7 and 8 (end of study)]

   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).

2. change in total score of the Clinical Global Impression Improvement Scale (CGI-S) [assessed from baseline, weeks 2, 4, 7 and 8 (end of study)]

   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.

3. change from randomization to each study visit in the total score of the Inventory of Depressive Symptomatology-Self Rated (IDS-SR30) [assessed on baseline visit, Week 2, 4, 6, and 8 (end of study).]

   A response is defined as a reduction in the IDS-SR30 score of ≥50% and remission is defined as a score of ≤14.

4. Adverse events [collected at baseline, weeks 1, 2, 3, 4, 6, 8 and 9 (follow up)]

   collected from signing informed consent through 7 days after the last dose of study treatment. Ascertained by qualified clinician.

5. Columbia Suicide Severity Rating Scale (C-SSRS) [assessed at baseline, weeks 2, 4, 6 and 8 (end of study)]

   administered by qualified clinician

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MSI Investigational Site	Birmingham	Alabama	United States	35216
2	MSI Investigational Site	Encino	California	United States	91316
3	MSI Investigational Site	Escondido	California	United States	92025
4	MSI Investigational Site	Garden Grove	California	United States	92845
5	MSI Investigational Site	Los Alamitos	California	United States	90720
6	MSI Investigational Site	Los Angeles	California	United States	90024
7	MSI Investigational Site	National City	California	United States	91950
8	MSI Investigational Site	Newport Beach	California	United States	92660
9	MSI Investigational Site	Oakland	California	United States	94612
10	MSI Investigational Site	Oceanside	California	United States	92056
11	MSI Investigational Site	Torrance	California	United States	90502
12	MSI Investigational Site	Jacksonville	Florida	United States	32256
13	MSI INvestigational Site	Kissimmee	Florida	United States	34741
14	MSI Investigational Site	Lauderhill	Florida	United States	33319
15	MSI Investigational Site	Orlando	Florida	United States	32806
16	MSI Investigational Site	Atlanta	Georgia	United States	30328
17	MSI Investigational Site	Hoffman Estates	Illinois	United States	60169
18	MSI Investigational Site	Towson	Maryland	United States	21285
19	MSI Investigational Site	Flowood	Mississippi	United States	39232
20	MSI Investigational Site	Las Vegas	Nevada	United States	89102
21	MSI Investigational Site	Marlton	New Jersey	United States	08053
22	MSI Investigational Site	Albuquerque	New Mexico	United States	87109
23	MSI Investigational Site	New York	New York	United States	10128
24	MSI Investigational Site	Rochester	New York	United States	14618
25	MSI Investigational Site	Canton	Ohio	United States	44718
26	MSI Investigational Site	Dayton	Ohio	United States	45417
27	MSI Investigational Site	Portland	Oregon	United States	97210
28	MSI Investigational Site	Memphis	Tennessee	United States	38119
29	MSI Investigational Site	Austin	Texas	United States	78731
30	MSI Investigational Site	Austin	Texas	United States	78754
31	MSI Investigational Site	Dallas	Texas	United States	75231
32	MSI Investigational Site	Houston	Texas	United States	77008
33	MSI Investigational Site	Houston	Texas	United States	77098
34	MSI Investigational Site	Murray	Utah	United States	84123
35	MSI Investigational Site	Bellevue	Washington	United States	98007

Sponsors and Collaborators

• MSI Methylation Sciences, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MSI Methylation Sciences, Inc.
• ClinicalTrials.gov Identifier: NCT01912196
• Other Study ID Numbers: MSI-CP.002
• First Posted: Jul 31, 2013
• Last Update Posted: Mar 18, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by MSI Methylation Sciences, Inc.: Depressive Disorder
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

No Results Posted as of Mar 18, 2016