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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)

Information source: Euthymics BioScience, Inc.
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Major Depressive Disorder

Intervention: EB-1010 25mg BID (Drug); SSRI Active (Drug); EB-1010 50mg BID (Drug); Placebo (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Euthymics BioScience, Inc.

Official(s) and/or principal investigator(s):
Pierre Tran, MD, Study Director, Affiliation: Euthymics BioScience, Inc.

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.

Clinical Details

Official title: A Double-Blind, 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) (Triple Reuptake Inhibitor Anti-Depressant Effects - TRIADE Study)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Change from baseline in MADRS Score

Secondary outcome: Change in Clinical Global Severity Scale

Eligibility

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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 17-item Hamilton Rating Scale for Depression (HAM-D-17) (whose

score is derived from the HAM-D-28)20 score ≥ 18 during the screening phase to qualify for inclusion. The HAM-D-28 will be administered by the study clinicians at the screening and baseline visits, and by remote, independent raters during the screening phase at the time of the SAFER interview.

- 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. Exclusion Criteria:

- 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.

- Patients who have received ECT in the past 20 years or Vagal Nerve/Deep Brain

Stimulation during their lifetime.

- Unstable medical illness including, cardiovascular, hepatic, renal, respiratory,

endocrine, neurological, or hematological disease.

- Subjects with evidence or history of significant neurological disorder, including

head trauma with loss of consciousness, history of stroke, Parkinson's disease, epilepsy disorder, conditions that lower seizure threshold, seizures of any etiology (including substance or drug withdrawal), who are taking medications to control seizures, or who have increased risk of seizures as evidenced by history of EEG with epileptiform activity (with the exception of juvenile febrile seizures).

- Subjects who are known to have AIDS or to be HIV positive.

- Patients with a significant history of drug or food allergy or hypersensitivity.

Specifically, patients who report a history of drug-induced and/or food-induced asthma, facial-swelling, tongue swelling, angioedema, urticaria, stridor, hives, epiglottis swelling, recurrent skin rashes, toxic epidermal necrolysis, or Stevens-Johnson Syndrome.

- Patients who, in the Investigator's judgment represent a significant risk of

committing suicide during the course of the trial based on history or evaluation of current mental status. Patients with significant hostility and history of aggressive acts who, in the Investigator's judgment, represent a significant risk of committing violent acts during the course of the trial based on history or evaluation of current mental status.

- Patients who have a history or evidence of a medical condition that would expose them

to an undue risk of a significant adverse event or interfere with assessments of safety or efficacy during the course of the trial.

- Patients with thyroid pathology (unless condition has been stabilized with

medications for at least the past three months).

- Patients with a lifetime history of serotonin syndrome.

- Patients with a significant history of a seizure disorder.

- Patients who have received a vaccination in the past three months.

- Patients with a recent (within two weeks) viral or systemic illness.

- Patients with current skin rashes.

- Patients who have recently (within two weeks) begun any medications.

- Patients who have a positive urine drug screen which cannot be explained by

prescribed medications.

- Patients with AST and/or ALT >2x ULN at the screening visit.

- Patients with abnormal thyroid-stimulating hormone (TSH) concentrations or positive

hepatitis tests.

- Patients with clinically significant laboratory abnormalities (hematology, chemistry,

urinalysis) or with Safety Values of Potential Clinical Concern (see Table 3).

- Diastolic blood pressure > 105 mmHg at screen or baseline.

- Any signs or symptoms that are, in the Investigator's judgment, medically

significant, in that they would impact the patient's safety.

- Patients with a QTc value of 460 ms or greater.

- Patients who are known to be allergic or hypersensitive to paroxetine and EB-1010.

- Patients previously treated with and not responding to paroxetine

- Monoamine oxidase inhibitors (e. g., Nardil, phenelzine, Parnate, tranylcypromine,

Marplan, isocarboxazide) treatment within the 2 weeks prior to enrollment.

- Patients who would likely require prohibited concomitant medications and/or other

depression treatment during the trial.

- Prisoners or subjects who are involuntarily incarcerated.

- Subjects who are compulsorily detained for treatment of either a psychiatric or

physical (e. g., infectious disease) illness.

- Patients who demonstrate a 25% or greater decrease in depressive symptoms as

reflected by the QIDS-SR19 total score from screen visit to baseline visit.

- Patients who plan to have elective surgeries during the course of the study.

- Patients with a history of antidepressant-induced hypomania or dysphoria.

- Patients who demonstrate a less than 80% compliance (as measured by pill count) of

their antidepressant medication during the Screening Phase.

Locations and Contacts

Pacific Clinical Research Medical Group, Arcadia, California 91007, United States

Southwest Research, Inc., Beverly Hills, California 90210, United States

Synergy Clinical Research Center, National City, California 91950, United States

Clinical Innovations, Inc., Santa Ana, California 92705, United States

Pacific Clinical Research Medical Group, Upland, California 91786, United States

Radiant Research, Inc., Denver, Colorado 80239, United States

Comprehensive Psychiatric Care, Norwich, Connecticut 06360, United States

Sanitas Research, Coral Gables, Florida 33134, United States

Clinical Neuroscience Solution, Inc., Jacksonville, Florida 32216, United States

Florida Clinical Research Center, Maitland, Florida 32751, United States

Clinical Neuroscience Solutions, Inc, Orlando, Florida 32806, United States

Medical Research Group of Central Florida, Sanford, Florida 32771, United States

Atlanta Center for Medical Research, Atlanta, Georgia 30308, United States

AMR Baber Research, Naperville, Illinois 60563, United States

Psychiatric Medicine Associates, Stokie, Illinois 60076, United States

Lake Charles Clinical Trials, Lake Charles, Louisiana 70601, United States

Clinical Insights, Glen Burnie, Maryland 21061, United States

Cambridge Health Alliance, Cambridge, Massachusetts 02139, United States

AccelRx Research, Fall River, Massachusetts 02721, United States

St Charles Psychiatric Associates, St. Charles, Missouri 63301, United States

Global Medical Institutes, Princeton, New Jersey 08540, United States

CRI Worldwide, LLC, Willingboro, New Jersey 08046, United States

Mount Sinai School of Medicine, New York, New York 10029, United States

Behavioral Medical Research of Staten Island, Staten Island, New York 10305, United States

Community Research, Cincinnati, Ohio 45227, United States

Midwest Clinical Research Center, Dayton, Ohio 45417, United States

North Star Medical Research, Middleburg Heights, Ohio 44130, United States

Neurology and Neuroscience Center of Ohio, Toledo, Ohio 43623, United States

SP Research, PLLC, Oklahoma City, Oklahoma 73112, United States

Lehigh Valley Hospital, Allentown, Pennsylvania 18103, United States

Southeastern PA Medical Institute, Broomall, Pennsylvania 19008, United States

Suburban Research Associates, Media, Pennsylvania 19063, United States

CRI Worldwide, Philadelphia, Pennsylvania 19139, United States

University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Scranton Counseling Center, Scranton, Pennsylvania 18503, United States

Radiant Research, Greer, South Carolina 29651, United States

Clinical NeuroScience Solutions, Inc., Memphis, Tennessee 38119, United States

Vanderbilt University Medical Center, Nashville, Tennessee 37212, United States

FutureSearch Trials of Dallas, Dallas, Texas 75231, United States

Radiant Research, Inc., Murray, Utah 84123, United States

Aspen Clinical Research, Orem, Utah 84058, United States

VCU, Richmond, Virginia 23219, United States

Dean Foundation for Health, Research & Education, Middleton, Wisconsin 53562, United States

Additional Information

Starting date: February 2011
Last updated: June 9, 2014

Page last updated: August 23, 2015

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