Efficacy and Safety Study of Lu AA21004 in Adults With Major Depressive Disorder - Full Text View

Purpose

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

Condition	Intervention	Phase
Depressive Disorder, Major	Drug: Lu AA21004 Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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 20 mg) of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder

Resource links provided by NLM:

MedlinePlus related topics: Depression

U.S. FDA Resources

Further study details as provided by Takeda:

Primary Outcome Measures:

Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
The change between MADRS total score at week 8 or final visit and MADRS score at baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.

Secondary Outcome 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. ] [ Designated as safety issue: No ]
The change between MADRS score at week 8 or final visit and MADRS score at baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
Mean Clinical Global Impression Scale-Improvement (CGI-I) score at Week 8. [ Time Frame: Week 8. ] [ Designated as safety issue: No ]
The CGI-I assesses the clinician's impression of the subject's state of mental illness improvement and consists of one question for the investigator: "Compared to his condition at the start of the study, how much has this patient changed?" which is rated on a seven-point scale (1=very much improved; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; 7=very much worse). Higher scores indicate greater severity of illness.
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. ] [ Designated as safety issue: No ]
The change between MADRS score at week 8 or final visit and MADRS score at baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms. HAM-A is a 14 item rating scale to quantify anxiety severity rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56.
MADRS remission at Week 8, with remission defined as a MADRS total score ≤10. [ Time Frame: Week 8. ] [ Designated as safety issue: No ]
MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
Change from Baseline in Sheehan Disability Scale (SDS) total score at Week 8 [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
The change between the SDS total score at week 8 or final visit and the total score collected at baseline. The SDS is a 3 item rating scale to assess functional impairment (panic, anxiety, phobic and depressive symptoms) over three inter-related domains (work/school, social life, and family life/home responsibilities) rated on an 11 point scale from 0 (not at all) to 10 (extremely) with a total score range from 0 to 30. Higher scores indicate greater severity of impairment.

Enrollment:	462
Study Start Date:	July 2010
Study Completion Date:	January 2012
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lu AA21004 10 mg QD	Drug: Lu AA21004 Lu AA21004 10 mg, capsules orally, once daily for up to 8 weeks.
Experimental: Lu AA21004 20 mg QD	Drug: Lu AA21004 Lu AA21004 20 mg, capsules, orally, once daily for up to 8 weeks.
Placebo Comparator: Placebo QD	Drug: Placebo Lu AA21004 placebo-matching capsules, orally, once daily for up to 8 weeks.

Detailed Description:

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 participants from approximately 35 sites in North America.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Suffers from a major depressive episode recurrent as the primary diagnosis according to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
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 previously participated in a Lu AA21004 clinical study.
Has 1 or more the following:
- Any current psychiatric disorder other than Major Depressive Disorder as defined in the DSM-IV
- Current or past history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder defined in the DSM-IV-TR.
- Diagnosis of alcohol or other substance disorder (except nicotine and caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least years prior to screening (participant must also have negative urine drug screen prior to Baseline).
- Presence or history of a clinically significant neurological disorder (including epilepsy)
- Neurodegenerative disorder.
- Any Axis II disorder that might compromise the study.
Has a thyroid stimulating hormone value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator.
Has clinically significant abnormal vital signs as determined by the investigator.
Has an abnormal Electrocardiogram.
Has an alanine aminotransferase, aspartate aminotransferase or total bilirubin level greater than 1.5 times the upper limits of normal.
Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication.
Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.
Has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.
Has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. For the purposes of this protocol the following conditions are considered unstable due to the potential impact on assessment of MDD response: pain disorder, chronic fatigue syndrome, fibromyalgia, and obstructive sleep apnea.
Has a significant risk of suicide according to the investigator's opinion.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01163266

Show 37 Study Locations

Sponsors and Collaborators

Takeda

Investigators

Study Director:

Senior Medical Director

Takeda

More Information

No publications provided

Responsible Party:	Takeda
ClinicalTrials.gov Identifier:	NCT01163266 History of Changes
Other Study ID Numbers:	LuAA21004_316, U1111-1115-8770
Study First Received:	July 14, 2010
Last Updated:	February 9, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Takeda:

Major Depressive Disorder
Depression
Melancholia
Drug Therapy

Additional relevant MeSH terms:

Depressive Disorder
Depression
Depressive Disorder, Major

Mood Disorders
Mental Disorders
Behavioral Symptoms

ClinicalTrials.gov processed this record on June 18, 2013