AZD7268 Safety and Tolerability Study

Study Overview
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Brief Summary
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The purpose of this study is to prove the principle that treatment with AZD7268 reduces depressive symptoms in patients with Major Depressive Disorder (MDD) compared with placebo.

Official Title
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A Phase II, Multi-center, Randomized, Double-bind, Double-dummy, Active and Placebo Controlled, Parallel Group Study to Assess the Efficacy and Safety of AZD7268 in Patients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: AZD7268
* Drug: Escitalopram
* Drug: Placebo capsules
* Drug: Placebo tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed, written, and dated Informed Consent prior to any study specific procedures Documented primary clinical diagnosis meeting criteria from the DSM-IV, Text Revision (APA 2000) for any of the following: 296.2x Major Depressive Disorder, Single Episode, or 296.3x Major Depressive Disorder, Recurrent Exclusion Criteria: Patients with a secondary DSM-IV Axis I disorder other than GAD or social anxiety disorder (as assessed by MINI), provided the primary diagnosis is MDD. This diagnosis should have been made at least 6 months before enrollment Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current psychiatric status Patients whose current episode of depression started less than 4 weeks before enrollment

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD7268<br>The AZD7268 15 mg BID arm consisted of 3 AZD7268 5 mg capsules dosed orally in the morning and evening. In addition, 2 placebo tablets to match encapsulated escitalopram tablets were dosed orally in the morning only. | Drug: AZD7268<br>* 15 mg, oral, twice daily (BID)<br>Drug: Placebo tablets<br>* Placebo tablets to match encapsulated escitalopram<br>|
| Placebo Comparator: Placebo<br>The placebo arm consisted of 3 placebo capsules to match AZD7268 capsules dosed orally in the morning and evening. In addition, 2 placebos to match encapsulated escitalopram tablets were dosed orally in the morning only. | Drug: Placebo capsules<br>* Placebo capsules to match AZD7268<br>Drug: Placebo tablets<br>* Placebo tablets to match encapsulated escitalopram<br>|
| Active Comparator: Escitalopram<br>The escitalopram 20 mg QD arm consisted of 3 placebo to match AZD7268 capsules dosed orally in the morning and evening. In addition, during Week 1, one encapsulated 10-mg escitalopram tablet and 1 placebo to match encapsulated escitalopram tablet were dosed orally in the morning only. During Weeks 2 through 4, two encapsulated 10-mg escitalopram tablets were dosed orally in the morning only. | Drug: Escitalopram<br>* 20 mg, oral, once daily (QD)<br>Drug: Placebo capsules<br>* Placebo capsules to match AZD7268<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From Baseline to Week 4. | MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). Change from baseline was calculated as Week 4 value minus baseline value. [observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)] | Baseline, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Åsberg Depression Rating Scale (MADRS) Response | Number of patients with MADRS response at Week 4. MADRS response is defined as >=50% reduction in MADRS total score from baseline. MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). MADRS response at Week 4 is calculated using last observation carried forward (LOCF). [Full Analysis Set (FAS)] | Week 4 | 
| Montgomery-Åsberg Depression Rating Scale (MADRS) Remission | Number of patients, who achieved MADRS remission at week 4. Remission is defined as a MADRS total score <= 10. MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). MADRS remission at Week 4 is calculated using last observation carried forward (LOCF). [Full Analysis Set (FAS)] | Week 4 | 
| Hamilton Rating Scale for Depression (HAM-D) Total Score Change From Baseline to Week 4. | HAM-D total score, sum of 17 item scores (each on a 0 to 2 or 0 to 4 scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 52 (the worst). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. [observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)] | Baseline, Week 4 | 
| Clinical Global Impression - Severity (CGI-S) Score Change From Baseline | CGI-S assesses global illness severity, i.e. the patient's current clinical state, on a continuous scale from 1 (Normal, not ill) to 7 (Among the most extremely ill patients). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. [observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)] | Baseline, Week 4 | 
| Hamilton Rating Scale for Anxiety (HAM-A) Total Score Change From Baseline | HAM-A total score, sum of 14 item scores (each on a 0 to 4 scale), assesses the severity of anxiety symptoms on a continuous scale from 0 (the best) to 52 (the worst). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. [observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)] | Baseline, Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression