Efficacy Study of Lu AA21004 for Treatment of Major Depressive Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01355081
First received: May 16, 2011
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

The purpose of this study is to assess the efficacy, safety and tolerability of 8-week treatment with Lu AA21004, once daily (QD), in Japanese participants with major depressive disorder.


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

Resource links provided by NLM:


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 score at week 8 or final visit relative to baseline. MADRS is a 10-item clinician rated scale that measures 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 relative to 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: 8 Weeks. ] [ 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 the Hamilton Depression Scale (HAM-D17) Total Score After 8 Weeks of Treatment [ Time Frame: 8 Weeks. ] [ Designated as safety issue: No ]
    The HAMD-17 is a 17-item rating scale that assesses depressed mood, agitation and somatic symptoms of depression, rated on a 5-point scale from 0 (absent) to 4 (very severe) with a total score range from 0 to 52. Higher scores indicate greater severity of depression symptoms.

  • Clinical Global Impression Scale-Improvement (CGI-I) Score After 8 Weeks of Treatment [ Time Frame: 8 Weeks. ] [ 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 After 8 Weeks of Treatment [ Time Frame: 8 Weeks. ] [ Designated as safety issue: No ]
    The change between the SDS total score at week 8 or final visit relative to 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: 366
Study Start Date: May 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo QD Drug: Placebo
Lu AA21004 placebo-matching tablets, orally, once daily for up to 8 weeks.
Experimental: Lu AA21004 5 mg QD Drug: Lu AA21004
Lu AA21004 5 mg, tablets, orally, once daily for up to 8 weeks.
Experimental: LuAA21004 10 mg QD Drug: Lu AA21004
Lu AA21004 10 mg, tablets, orally, once daily for up to 8 weeks.

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 approximately 2-fold higher prevalence in women than in men. 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. In addition to direct ill effects, MDD causes suicide or job loss and exerts indirect influence on social economy.

This study will assess the efficacy and the safety of Lu AA21004. This study consists of a 1-week screening period, an 8-week double-blind treatment period, 4-week s safety follow-up.The duration of the study is 13 weeks in total. 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 complete the 8-week double-blind treatment period can successively enter a long-term extension study (Lu AA21004/OCT-001; NCT01395147; hereinafter, OCT-001), if they meet all inclusion criteria and none of exclusion criteria of the OCT-001 study and are willing to participate in the OCT-001 study.

Subjects who will enter the OCT-001 will not be requested to safety follow-up after completion of the 8-week double-blind treatment period.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. The subject has one or more of the following conditions:

    • Any current psychiatric disorder other than MDD as defined in the DSM-IV-TR. 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.
    • 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.
  2. 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.
  3. The subject is at significant risk of suicide or has a score ≥5 on Item 10 (suicidal thoughts) of the MADRS at the Screening and Baseline Visit, or has attempted suicide within 6 months prior to the Screening Visit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01355081

Locations
Japan
Inzai-shi, Chiba, Japan
Noda-City, Chiba, Japan
Fukuoka-city, Fukuoka, Japan
Kitakyushu-shi, Fukuoka, Japan
Annaka-shi, Gunma, Japan
Fujioka-shi, Gunma, Japan
Takasaki-shi, Gunma, Japan
Hatsukaichi-shi, Hiroshima, Japan
Hiroshima-shi, Hiroshima, Japan
Sapporo-Shi, Hokkaido, Japan
Amagasaki-shi, Hyogo, Japan
Kobe-shi, Hyogo, Japan
Fujisawa-shi, Kanagawa, Japan
Kawasaki-shi, Kanagawa, Japan
Sagamihara-shi, Kanagawa, Japan
Yokohama-shi, Kanagawa, Japan
Osaka-shi, Kita-ku, Japan
Kumamoto-shi, Kumamoto, Japan
Kyoto-shi, Kyoto, Japan
Kurashiki-shi, Okayama, Japan
Osaka-shi, Osaka, Japan
Fukaya-shi, Saitama, Japan
Saitama-city, Saitama, Japan
Utsunomiya-shi, Tochigi, Japan
Anan-shi, Tokushima, Japan
Tokushisma-shi, Tokushima, Japan
Hachioji-shi, Tokyo, Japan
Katsushika-ku, Tokyo, Japan
Musashino-shi, Tokyo, Japan
Nanyo-shi, Yamagata, Japan
Ibaraki, Japan
Tokyo, Japan
Sponsors and Collaborators
Takeda
Investigators
Study Director: Senior Manager Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01355081     History of Changes
Other Study ID Numbers: LuAA21004/CCT-003, U1111-1120-9277, JapicCTI-111492
Study First Received: May 16, 2011
Last Updated: December 10, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Takeda:
Drug Therapy

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms

ClinicalTrials.gov processed this record on July 24, 2014