Efficacy and Safety Study of Lu AA21004 for Treatment of Major Depressive Disorder - Full Text View

Purpose

The purpose of this study is to assess the efficacy and safety of multiple doses of Lu AA21004, once daily (QD), in subjects with major depressive disorder.

Condition	Intervention	Phase
Depressive Disorder, Major	Drug: Lu AA21004 Drug: Placebo	Phase 2 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 Multinational, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Assess the Efficacy and Safety of Lu AA21004 in Patients With Major Depressive Disorder

Resource links provided by NLM:

MedlinePlus related topics: Depression

U.S. FDA Resources

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:

Change from Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score. [ 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.

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.
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.
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 Sheehan Disability Scale (SDS) total score at Week 8. [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
The change between the Sheehan Disability Scale total score at week 8 or final visit and the total score collected at baseline. The Sheehan Disability Scale 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:	600
Study Start Date:	November 2010
Study Completion Date:	April 2012
Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lu AA21004 5 mg QD	Drug: Lu AA21004 Lu AA21004 5 mg, tablets, orally, once daily for up to 8 weeks during double blind treatment period.
Experimental: Lu AA21004 10 mg QD	Drug: Lu AA21004 Lu AA21004 10 mg, tablets, orally, once daily for up to 8 weeks during double blind treatment period.
Experimental: Lu AA21004 20 mg QD	Drug: Lu AA21004 Lu AA21004 10 mg, tablets, orally, once daily for up to 1 week, followed by Lu AA21004 20 mg, tablets, orally, once daily for up to 7 weeks during double blind treatment period.
Placebo Comparator: Placebo QD	Drug: Placebo Lu AA21004 placebo-matching tablets, orally, once daily for up to 8 weeks during double blind treatment period.

Detailed Description:

Lu AA21004 was discovered by H. Lundbeck A/S, and is under co-development by H. Lundbeck A/S and Takeda for the treatment of major depressive disorder and general anxiety disorder.

Major depressive disorder (MDD) is a chronic, recurring disease with considerable morbidity in the general population. The estimated lifetime prevalence of major depression in the adult population is 5 to 25%, with a higher prevalence in women (10 to 25%) than in men (5 to 12%). The hallmark of the disease is a depressed mood, with additional symptoms including sleep disturbances, psychomotor agitation or retardation, sexual dysfunction, weight loss, concentration difficulties and delusional ideas. Anxiety symptoms are common; however, the most serious complication of a depressive episode is emergence of suicidal ideation and behavior.

This study will be conducted to assess the efficacy and the safety of three fixed doses of Lu AA21004 in order to establish the appropriate clinical effective dose range. Blood samples will be collected from participants, and a safety follow-up contact (visit or phone call) will be made 4 weeks after completion of the 8-week double-blind treatment period.

Subjects who prematurely discontinue the study during the 8-week double-blind treatment period will be requested to visit the study site for a withdrawal visit as soon as possible and will be contacted for a safety follow-up assessment 4 weeks after withdrawal.

The total duration of the study is 13 weeks in total.

Eligibility

Ages Eligible for Study:	20 Years to 64 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The subject suffers from Major Depressive Disorder as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.2x and 296.3x).
The reported duration of the current major depressive episode is at least 3 months at the Screening Visit.
The subject has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26 at the Screening and Baseline Visits.
The subject has a Clinical Global Impression Scale-Severity (CGI-S) score ≥4 at the Screening and Baseline Visits.

Exclusion Criteria:

The subject has one or more of the following conditions:
- Any current psychiatric disorder other than Major Depressive Disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR; assessed by the Mini International Neuropsychiatric Interview: MINI). A subject who exhibits symptoms of anxiety is eligible unless the subject fulfills the diagnostic criteria for a current anxiety disorder per DSM-IV-TR.
- Current diagnosis or 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 as defined in the DSM-IV-TR.
- Current diagnosis or history of any substance-related disorder (except nicotine and caffeine-related disorders) as defined in the DSM-IV-TR. Subject with confirmed positive urine drug screens (except prescribed medications or a medication that does not constitute drug abuse) will be excluded.
- Presence or history of a clinically significant neurological disorder (including epilepsy).
- Neurodegenerative disorder. (Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, etc.)
- Any DSM-IV-TR axis II disorder that might compromise the study.
The current depressive symptoms of the subject are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
The subject has received electroconvulsive, vagal nerve stimulation, or repetitive transcranial magnetic stimulation therapy within 6 months prior to the Screening Visit.
The subject is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study.
The subject is at significant risk of suicide or has a score ≥5 on Item 10 (suicidal thoughts) of the MADRS, or has attempted suicide within 6 months prior to the Screening Visit.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01255787

Show 73 Study Locations

Sponsors and Collaborators

Takeda Pharmaceutical Company Limited

Investigators

Study Director:

Senior Medical Director Clinical Science

Takeda Global Research & Development Center, Inc.

More Information

No publications provided

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Takeda Pharmaceutical Company Limited )
ClinicalTrials.gov Identifier:	NCT01255787 History of Changes
Other Study ID Numbers:	LuAA21004/CCT-002, 2010-022257-41, U1111-1117-6595, JapicCTI-101344, CTRI/2011/08/001963
Study First Received:	December 6, 2010
Last Updated:	December 15, 2012
Health Authority:	Japan: Pharmaceuticals and Medical Devices Agency Croatia: Agency for Medicinal Product and Medical Devices Finland: Finnish Medicines Agency Germany: Federal Institute for Drugs and Medical Devices Latvia: State Agency of Medicines Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Romania: National Agency for Medicines and Medical Devices Russia: Department of State Regulation of Circulation of Medical Remedies Serbia and Montenegro: Agency for Drugs and Medicinal Devices Ukraine: State Pharmacological Center - Ministry of Health Hong Kong: Department of Health India: Drugs Controller General of India South Korea: Korea Food and Drug Administration (KFDA) Malaysia: National Pharmaceutical Control Bureau Philippines : Food and Drug Administration Taiwan: Taiwan Food and Drug Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:

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 May 16, 2013