AZD7268 Safety and Tolerability Study

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: AZD7268; Drug: Placebo tablets; Drug: Placebo capsules; Drug: Escitalopram

• Study Type: Interventional
• Enrollment (Actual): 247
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Research Site
  • California
    • Garden Grove, California, United States
      • Research Site
    • San Diego, California, United States
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States
      • Research Site
  • Florida
    • Bradenton, Florida, United States
      • Research Site
    • Jacksonville, Florida, United States
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States
      • Research Site
  • Maryland
    • Rockville, Maryland, United States
      • Research Site
  • New York
    • Cedarhurst, New York, United States
      • Research Site
    • New York, New York, United States
      • Research Site
    • Rochester, New York, United States
      • Research Site
  • Ohio
    • Dayton, Ohio, United States
      • Research Site
  • Oregon
    • Portland, Oregon, United States
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States
      • Research Site
  • Texas
    • Friendswood, Texas, United States
      • Research Site
  • Washington
    • Bellevue, Washington, United States
      • Research Site
    • Seattle, Washington, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AZD7268; 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; 15 mg, oral, twice daily (BID); Drug: Placebo tablets; Placebo tablets to match encapsulated escitalopram
PLACEBO_COMPARATOR: Placebo; 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 tablets; Placebo tablets to match encapsulated escitalopram; Drug: Placebo capsules; Placebo capsules to match AZD7268
ACTIVE_COMPARATOR: Escitalopram; 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: Placebo capsules; Placebo capsules to match AZD7268; Drug: Escitalopram; 20 mg, oral, once daily (QD)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (ACTUAL): April 1, 2010
• Study Completion (ACTUAL): April 1, 2010

Study Registration Dates

• First Submitted: November 25, 2009
• First Submitted That Met QC Criteria: November 25, 2009
• First Posted (ESTIMATE): November 26, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): April 17, 2012
• Last Update Submitted That Met QC Criteria: April 11, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: D1151C00005