A Paroxetine- and Placebo-Controlled Study of 50 mg/Day and 100 mg/Day of EB-1010 Among Outpatients With Major Depressive Disorder Who Have Responded Inadequately to Prior Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

NCT01318434 | Completed Phase 2

• 1 other identifier: EB-1010-301
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 43

Brief Summary

The main research hypothesis for this study is that, among patients with Major Depressive Disorder (MDD) who have responded inadequately to treatment with SSRIs or SNRIs, the degree of improvement, as measured by the change from baseline of the Montgomery-Asberg Depression Rating Scale (MADRS)will be significantly greater among patients treated with EB-1010 (at the dose of 50 mg/day or 100 mg/day) than among those treated with placebo using the sequential parallel comparison design. The secondary research hypothesis for this study is that, among patients with MDD who have responded inadequately to treatment with SSRIs or SNRIs, the degree of improvement in depressive symptoms, as assessed by the MGH Cognitive and Physical Functioning Questionnaire (MGH CPFQ) will be significantly greater among those treated with EB-1010 (50 mg/day or 100 mg/day) than those treated with the SSRI paroxetine.

Conditions

Major Depressive Disorder

Keywords

Outpatient

Outcome Measures

Primary Outcomes (1)

• Change from baseline in MADRS Score

  Improvement in MADRS Score

  6 weeks

Secondary Outcomes (1)

• Change in Clinical Global Severity Scale

  6 weeks

Study Arms (4)

EB-1010 25 mg BID

EXPERIMENTAL

Experimental Active

Drug: EB-1010 25mg BID

EB-1010 50 mg BID

EXPERIMENTAL

Experimental Active

Drug: EB-1010 50mg BID

SSRI/SNRI

ACTIVE COMPARATOR

Active Comparator

Drug: SSRI Active

EB-1010 0 mg BID

PLACEBO COMPARATOR

Placebo comparator

Drug: Placebo

Interventions

EB-1010 25mg BID DRUG

capsule once daily

EB-1010 25 mg BID

SSRI Active DRUG

Active Comparator

SSRI/SNRI

EB-1010 50mg BID DRUG

Experimental Active

EB-1010 50 mg BID

Placebo DRUG

Placebo comparator

EB-1010 0 mg BID

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be able to give informed consent, (as required by IRB/IEC), prior to the initiation of any protocol required procedures.
• Patients must be able to understand the nature of the study, agree to comply with the prescribed dosage regimens, report for regularly scheduled office visits, and communicate to study personnel about adverse events and concomitant medication use.
• Patients with a diagnosis of major depressive episode as defined by DSM-IV-TR criteria, based on the SCID-CT29; their major depressive episode must be deemed "valid" using the SAFER criteria interview24 administered by remote, independent raters.
• Patients who have reported a history for the current depressive episode of an inadequate response to 1 and no more than 1 adequate SSRI or SNRI treatment. An inadequate response is defined as less than a 50% reduction in depressive symptom severity, as assessed by the MGH ATRQ administered by remote, independent raters. An adequate trial is defined as an antidepressant treatment for at least 8 weeks duration at least at the minimum dose as specified in the MGH ATRQ.
• Patients must have a Body Mass Index (BMI) of approximately 18-40.
• Patients must be able to be reliably rated on the psychiatric scales required by the protocol based on Investigator's judgment.
• Patients must be able to understand and read English.
• Placebo non-responders are defined as those patients who failed to achieve at least a 50% decrease in their MADRS score at visit 8 (Week 6), AND have a MADRS score of = or \> 16 at visit 8 (Week 6)
• Men and women, ages 18 to 65 inclusive.
• Meet DSM-IV-TR criteria (by Structured Clinical Interview for DSM-IV-TR - SCID-CT) for MDD, current.
• Treated with one of the allowed SSRIs or SNRIs at adequate doses (defined as 20mg/day or more of citalopram; 10 mg/day or more of escitalopram, 50mg/day or more of sertraline; 125 mg/day or more of venlafaxine; 60 mg/day or more of duloxetine) during the current episode for at least 8 weeks, with the same, adequate dose over the last 4 weeks.
• Between the screen and baseline visits, patients must be documented to have less than a 25% reduction in QIDS-SR score.
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. Adequate methods are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectable or patch hormonal contraception, oral contraceptives, an IUD, double-barrier contraception, sexual abstinence. Form of birth control will be documented at screening and baseline.
• WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ³ 12 consecutive months); or women on hormone replacement therapy \[HRT\] with documented serum follicle stimulating hormone \[FSH\] level \> 35 mIU/mL). Even women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product.

You may not qualify if:

• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period \[and for up to 4 weeks after the last dose of investigational product.
• WOCBP using a prohibited contraceptive method that does not meet established and acceptable medical standards.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or prior to investigational product administration.
• Sexually active fertile men not using effective birth control if their partners are WOCBP.
• Patients who do not report any prior inadequate response (equal or greater than 50% decrease in depressive symptom severity) or report an inadequate response (less than 50% decrease in depressive symptom severity) to more than 1 prior adequate trials of antidepressant treatments during the current depressive episode (including monotherapy treatment and distinct combination regimens) at a therapeutic dose (as defined by the MGH ATRQ)22-23 and for an adequate duration (minimum 6 weeks for any monotherapy).
• Patients who report treatment with adjunctive medication (buspirone, atypical antipsychotics, lithium) to their antidepressant therapy for a minimum of 4 weeks during the current depressive episode.
• Patients with a current need for involuntary commitment or who have been hospitalized within 4 weeks of the Screening Visit for the current major depressive episode.
• Subjects with other DSM-IV-TR Axis I disorders other than Generalized Anxiety Disorder (GAD: 300.02), Social Anxiety Disorder (300.23), or Specific Phobia (300.29). Subjects with co-morbid GAD, Social Anxiety Disorder, or Specific Phobia are ineligible if the co-morbid condition is clinically unstable, requires treatment, or has been the primary focus of treatment within the 6 month period prior to screening. More specifically, patients who have a current Axis I diagnosis
• Patients experiencing hallucinations, delusions, or any psychotic symptomatology in the current or any previous depressive episode.
• Patients who have met DSM-IV-TR criteria for any significant substance use disorder within the past six months, based on the SCID-CT.
• Patients receiving new-onset psychotherapy and/or somatic therapy (light therapy, trans-cranial magnetic stimulation) within 6 weeks of screening, or at any time during participation in the trial.
• Patients who, in the opinion of the Investigator, are actively suicidal and at significant risk for suicide.
• Patients who have participated in any clinical trial with an investigational drug or device within the past month.
• Patients who routinely perform shift work and whose sleep-wake cycle is frequently changed because of their work.

Sponsors & Collaborators

• Euthymics BioScience, Inc.: lead

Study Sites (43)

Pacific Clinical Research Medical Group

Arcadia, California, 91007, United States

Location

Southwest Research, Inc.

Beverly Hills, California, 90210, United States

Location

Synergy Clinical Research Center

National City, California, 91950, United States

Location

Clinical Innovations, Inc.

Santa Ana, California, 92705, United States

Location

Pacific Clinical Research Medical Group

Upland, California, 91786, United States

Location

Radiant Research, Inc.

Denver, Colorado, 80239, United States

Location

Comprehensive Psychiatric Care

Norwich, Connecticut, 06360, United States

Location

Sanitas Research

Coral Gables, Florida, 33134, United States

Location

Clinical Neuroscience Solution, Inc.

Jacksonville, Florida, 32216, United States

Location

Florida Clinical Research Center

Maitland, Florida, 32751, United States

Location

Clinical Neuroscience Solutions, Inc

Orlando, Florida, 32806, United States

Location

Medical Research Group of Central Florida

Sanford, Florida, 32771, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30308, United States

Location

AMR Baber Research

Naperville, Illinois, 60563, United States

Location

Psychiatric Medicine Associates

Stokie, Illinois, 60076, United States

Location

Lake Charles Clinical Trials

Lake Charles, Louisiana, 70601, United States

Location

Clinical Insights

Glen Burnie, Maryland, 21061, United States

Location

Cambridge Health Alliance

Cambridge, Massachusetts, 02139, United States

Location

AccelRx Research

Fall River, Massachusetts, 02721, United States

Location

St Charles Psychiatric Associates

Saint Charles, Missouri, 63301, United States

Location

Global Medical Institutes

Princeton, New Jersey, 08540, United States

Location

CRI Worldwide, LLC

Willingboro, New Jersey, 08046, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Behavioral Medical Research of Staten Island

Staten Island, New York, 10305, United States

Location

Community Research

Cincinnati, Ohio, 45227, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

North Star Medical Research

Middleburg Heights, Ohio, 44130, United States

Location

Neurology and Neuroscience Center of Ohio

Toledo, Ohio, 43623, United States

Location

SP Research, PLLC

Oklahoma City, Oklahoma, 73112, United States

Location

Lehigh Valley Hospital

Allentown, Pennsylvania, 18103, United States

Location

Southeastern PA Medical Institute

Broomall, Pennsylvania, 19008, United States

Location

Suburban Research Associates

Media, Pennsylvania, 19063, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

CRI Worldwide

Philadelphia, Pennsylvania, 19139, United States

Location

Scranton Counseling Center

Scranton, Pennsylvania, 18503, United States

Location

Radiant Research

Greer, South Carolina, 29651, United States

Location

Clinical NeuroScience Solutions, Inc.

Memphis, Tennessee, 38119, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

FutureSearch Trials of Dallas

Dallas, Texas, 75231, United States

Location

Radiant Research, Inc.

Murray, Utah, 84123, United States

Location

Aspen Clinical Research

Orem, Utah, 84058, United States

Location

VCU

Richmond, Virginia, 23219, United States

Location

Dean Foundation for Health, Research & Education

Middleton, Wisconsin, 53562, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

1-(3,4-dichlorophenyl)-3-azabicyclo-(3.1.0)hexane hydrochloride; BID protein, human

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Pierre Tran, MD

  Euthymics BioScience, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2011
• First Posted: March 18, 2011
• Study Start: February 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: December 4, 2015

Record last verified: 2015-11

Locations

US (43)