A Comparison of Sertraline-reboxetine Combination Therapy Versus Sertraline or Reboxetine Monotherapy in the Treatment of Major Depression.

Study Overview
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Brief Summary
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This study was designed to determine if the novel combination of the SSRI, sertraline, and the NRI reboxetine will increase antidepressant efficacy without sacrificing the favorable safety profile of SSRIs.

Official Title
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Sertraline/[S,S]-Reboxetine Combination Versus Sertraline And [S,S]-Reboxetine Monotherapy In Major Depressive Disorder (MDD) In A Double-Blind, Placebo-Controlled, Eight Week Study.

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Drug: sertraline/[S,S]-reboxetine
* Drug: sertraline/[S,S]-reboxetine
* Drug: sertraline
* Drug: sertraline
* Drug: sertraline/[S,S]-reboxetine
* Drug: Placebo
* Drug: sertraline/[S,S]-reboxetine
* Drug: [S,S]-reboxetine monotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must fulfill the criteria for MDD without psychotic features as defined by DSMIV, based on clinical assessment and confirmed by Structural Clinical Interview for DSM-IV Axis I Disorder-Clinical Version (SCID-I) plus the MDD Specifiers included in the Research Version of SCID-I. HAM-D (17-item) ≥ 22 at Screening (Visit 1) and > 20 at Baseline (Visit 2). Minimum CGI-S ≥ 4 at Screening (Visit 1) and at Baseline (Visit 2). Exclusion Criteria: Known failure to satisfactory respond after adequate dose and duration (12 weeks) of treatment with clomipramine and one SSRI, or with two or more SSRIs. Subjects with > 20% HAM-D (17-item) improvement (decrease) from Screening (Visit 1) at Baseline (Visit 2). Subjects with uncorrected hypothyroidism or hyperthyroidism.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sertraline/[S,S]-Reboxetine-satellite150/4<br> | Drug: sertraline/[S,S]-reboxetine<br>* Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/4mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/4mg [S,S]-reboxetine for 5 and one half weeks.<br>|
| Experimental: Sertraline/[S,S]-Reboxetine-satellite150/6<br> | Drug: sertraline/[S,S]-reboxetine<br>* Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/4mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/6mg [S,S]-reboxetine for 5 and one half weeks.<br>|
| Active Comparator: sertraline-satellite<br> | Drug: sertraline<br>* Tablets, 50 mg/day orally for 3 days, followed by 100 mg/day orally for 4 and one half weeks, followed by 150 mg/day orally for 3 weeks.<br>|
| Active Comparator: sertraline-main<br> | Drug: sertraline<br>* Tablets, 50 mg/day orally for 3 days, followed by 100 mg/day orally for 4 and one half weeks, followed by 150 mg/day orally for 3 weeks<br>|
| Experimental: Sertraline/[S,S]-Reboxetine-satellite150/2<br> | Drug: sertraline/[S,S]-reboxetine<br>* Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/2mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/2mg [S,S]-reboxetine for 5 and one half weeks.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Tablets, orally once per day for 8 weeks<br>|
| Experimental: Sertraline/[S,S]-Reboxetine-main<br> | Drug: sertraline/[S,S]-reboxetine<br>* Tablets, 50mg sertraline/2mg [S,S]-reboxetine orally for 3 days, followed by 100mg sertraline/2mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/2mg [S,S]-reboxetine for 5 and one half weeks<br>|
| Active Comparator: [S,S]-reboxetine-main<br> | Drug: [S,S]-reboxetine monotherapy<br>* Tablets, 2 mg/day orally for 3 days, followed by 4 mg/day orally for 4 and one half weeks, followed by 6mg/day for 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from Baseline up to Week 8 (Visit 9) in the Montgomery-Asberg Depression Rating Scale (MADRS) total score as measured by a mixed concentration, suicidal ideation and restlessness. |  | visits 1-9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in HAM-D (17-item) total score |  | Weeks 1, 2, 3, 5, 6, and 8 | 
| Change from Baseline in the Hamilton Anxiety Rating Scale (HAM-A) and Apathy Evaluation Scale (AES) |  | Weeks 5 and 8 | 
| The frequency and severity of treatment-emergent adverse events, ECG changes, laboratory and vital signs changes by treatment group using descriptive statistics. |  | Weeks 1, 2, 3, 5, 6, and 8 | 
| Change from Baseline in MADRS total score |  | Weeks 1, 2, 3, 5, 6, and 8 |