Efficacy and Safety of Lu AA21004 in Adults With Major Depressive Disorder

Official Title: “A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses (10 and 15 mg) of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder”

The purpose of this study is to evaluate the efficacy, safety and tolerability of Lu AA21004, once daily (QD), compared with placebo in adults with major depressive disorder.

Depression has been recognized as a chronic illness that imposes a significant burden on individuals, families and society. Major depressive disorder (MDD) is among the most important causes of disability worldwide, in both developing and developed countries. Major depressive disorder is reported to be the most common mood disorder, with a lifetime prevalence of about 15% and as high as 25% in women. Major depressive disorder is characterized by the presence of 1 or more major depressive episodes that presents with depressed mood, loss of interest or pleasure, disturbed sleep or appetite, low energy, feelings of guilt or low self-worth and poor concentration.

Studies suggest that at least 70% of depressed patients also report somatic symptoms such as pain, shortness of breath, fatigue, or nausea. A number of patients may present with somatic symptoms as the main complaint rather than depressed mood. Depression is recurrent in 75% to 80% of patients, becomes chronic (ie, lasting 2 years or longer) in 15% to 20% of depressed patients, and can lead to substantial impairments in an individual's ability to take care of his or her everyday responsibilities. Furthermore, depression may lead to suicide and the mortality due to suicide is approximately 15% among patients treated by psychiatrists. Major depressive disorder imposes a socioeconomic burden comparable to chronic medical illnesses in terms of healthcare utilization, decreased productivity, and dysfunctional family life, and is associated with an increased consumption of general medical, psychiatric and emergency services.

Lu AA21004 is a compound under development by Takeda Pharmaceutical Company Limited and H.

Lundbeck A/S with clinical development for the treatment of major depressive disorder.

This study will involve approximately 450 subjects from approximately 35 sites in North America.

Intervention(s) in this Clinical Trial

• Drug: LuAA21004
  • LuAA21004 10 mg, capsules orally, once daily for up to 8 weeks.
• Drug: LuAA21004
  • LuAA21004 15 mg, capsules, orally, once daily for up to 8 weeks.
• Drug: Placebo
  • LuAA21004 placebo-matching capsules, orally, once daily for up to 8 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: LuAA21004 10 mg QD
• Experimental: LuAA21004 15 mg QD
• Placebo Comparator: Placebo QD

Primary Measures

• Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score.
  • Time Frame: Baseline and Week 8.
    Safety Issue?: No

Secondary Measures

• MADRS response at Week 8, with response defined as a ≥50% decrease in the MADRS total score from Baseline.
  • Time Frame: Baseline and Week 8.
    Safety Issue?: No
• Mean Clinical Global Impression Scale - Improvement (CGI-I) score at Week 8.
  • Time Frame: Week 8.
    Safety Issue?: No
• Change from Baseline in MADRS total score at Week 8 in subjects with baseline Hamilton Anxiety scale (HAM-A) total score ≥20.
  • Time Frame: Baseline and Week 8.
    Safety Issue?: No
• MADRS remission at Week 8, with remission defined as a MADRS total score ≤10.
  • Time Frame: Week 8.
    Safety Issue?: No
• Change from Baseline in Sheehan Disability Scale (SDS) Total Score.
  • Time Frame: Baseline and Week 8.
    Safety Issue?: No

Inclusion Criteria:

• Suffers from a major depressive episode (MDE) recurrent as the primary diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth
• Edition, Text Revision (DSM-IV-TR) criteria.
• The reported duration of the current MDE is at least 3 months.
• Has a MADRS total score of 26 or greater at Screening and Baseline Visits.
• Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits.

Exclusion Criteria:

• Has received Lu AA21004 in a previous clinical study.
• Has any current psychiatric disorder other than major depressive disorder, current or past history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition.
• Has any substance disorder (except nicotine and caffeine).
• Presence or history of a clinically significant neurological disorder.
• Has any Axis II disorder that might compromise the study.
• Current depressive symptoms are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
• Has a clinically significant unstable illness.
• Has 1 or more laboratory value outside the normal range.
• Has a thyroid stimulating hormone value outside the normal range.
• Has clinically significant abnormal vital signs.
• Has an abnormal electrocardiogram.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Takeda Global Research & Development Center, Inc. Industry

Overall Clinical Trial Officials and Contacts

Sr. Medical Director Study Director Takeda Global Research & Development Center, Inc.  

Overall Contact: Takeda Study Registration Call Center 800-778-2860 medicalinformation@tpna.com

Information obtained from ClinicalTrials.gov on February 02, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01179516

Study ID Number: LuAA21004_317

ClinicalTrials.gov Identifier: NCT01179516

Health Authority: United States: Food and Drug Administration