Clinical trial NCT01355081: Efficacy Study of Vortioxetine (Lu AA21004) for Treatment of Major Depressive Disorder
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase III Study to Assess the Efficacy and Safety of Lu AA21004 in Patients With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-05-17
Enrollment: 366
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

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 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.

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 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 Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26 at the Screening and Baseline Visits.
4. The subject has a Clinical Global Impression Scale-Severity (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.

Primary outcomes:
measure: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score After 8 Weeks of Treatment
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Percentage of Patients With MADRS Response After 8 Weeks of Treatment
timeFrame: Baseline, Week 8
measure: Percentage of Patients With MADRS Remission After 8 Weeks of Treatment
timeFrame: Week 8
measure: Change From Baseline in the Hamilton Depression Scale (HAM-D17) Total Score After 8 Weeks of Treatment
timeFrame: Baseline, Week 8
measure: Clinical Global Impression Scale-Improvement (CGI-I) Score After 8 Weeks of Treatment
timeFrame: Baseline, Week 8
measure: Change From Baseline in Sheehan Disability Scale (SDS) Total Score After 8 Weeks of Treatment
timeFrame: Baseline, Week 8
Other outcomes:
Locations:
city: Inzai-shi
country: Japan
state: Chiba
city: Noda-City
country: Japan
state: Chiba
city: Fukuoka-city
country: Japan
state: Fukuoka
city: Kitakyushu-shi
country: Japan
state: Fukuoka
city: Annaka-shi
country: Japan
state: Gunma
city: Fujioka-shi
country: Japan
state: Gunma
city: Takasaki-shi
country: Japan
state: Gunma
city: Hatsukaichi-shi
country: Japan
state: Hiroshima
city: Hiroshima-shi
country: Japan
state: Hiroshima
city: Sapporo-Shi
country: Japan
state: Hokkaido
city: Amagasaki-shi
country: Japan
state: Hyogo
city: Kobe-shi
country: Japan
state: Hyogo
city: Fujisawa-shi
country: Japan
state: Kanagawa
city: Kawasaki-shi
country: Japan
state: Kanagawa
city: Sagamihara-shi
country: Japan
state: Kanagawa
city: Yokohama-shi
country: Japan
state: Kanagawa
city: Osaka-shi
country: Japan
state: Kita-ku
city: Kumamoto-shi
country: Japan
state: Kumamoto
city: Kyoto-shi
country: Japan
state: Kyoto
city: Kurashiki-shi
country: Japan
state: Okayama
city: Osaka-shi
country: Japan
state: Osaka
city: Fukaya-shi
country: Japan
state: Saitama
city: Saitama-city
country: Japan
state: Saitama
city: Utsunomiya-shi
country: Japan
state: Tochigi
city: Anan-shi
country: Japan
state: Tokushima
city: Tokushisma-shi
country: Japan
state: Tokushima
city: Hachioji-shi
country: Japan
state: Tokyo
city: Katsushika-ku
country: Japan
state: Tokyo
city: Musashino-shi
country: Japan
state: Tokyo
city: Nanyo-shi
country: Japan
state: Yamagata
city: Ibaraki
country: Japan
city: Tokyo
country: Japan
Study officials:
affiliation: Takeda
name: Senior Manager
role: STUDY_DIRECTOR
References:
citation: Inoue T, Nishimura A, Sasai K, Kitagawa T. Randomized, 8-week, double-blind, placebo-controlled trial of vortioxetine in Japanese adults with major depressive disorder, followed by a 52-week open-label extension trial. Psychiatry Clin Neurosci. 2018 Feb;72(2):103-115. doi: 10.1111/pcn.12623. Epub 2017 Dec 27.