Clinical trial NCT01395147: Long-Term Extension Study of Lu AA21004 in Participants With Major Depressive Disorder
Official title: An Open-label, Long-Term Extension Study to Assess the Safety and Efficacy of Lu AA21004 in Patients With Major Depressive Disorder (Extension to Lu AA21004/CCT-003 Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-07-15
Enrollment: 119
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and efficacy of Lu AA21004 in participants with major depressive disorder after completion of an 8-week double-blind treatment period in a preceding study (Lu AA21004/CCT-003; NCT01355081).

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 long-term extension study will assess the safety and efficacy of 52-week treatment with Lu AA21004 in participants with major depressive disorder after completion of the 8-week double-blind treatment period in the preceding study (LuAA21004/CCT-003; NCT01355081; hereinafter referred to as CCT-003). This study will be conducted at the same institutions as CCT-003.

This study will include participants who completed the 8-week double-blind treatment period in CCT-003, and who meet all of the inclusion criteria, and do not meet any of the exclusion criteria of the long-term study. Visit 1 in this study will be the last visit (Visit 7) during the 8-week double-blind treatment period in CCT-003. Participants will start 2-week treatment with 10 mg/day of Lu AA21004 on the day after completion of the 8-week double-blind treatment period in CCT-003. The dose may then be decreased to 5 mg/day or increased to 20 mg/day according to the responses and symptoms of the participants. A dose increase, however, will be allowed only if the Clinical Global Impression (CGI) score meets the criteria for dose increases and the investigator or sub-investigator considers it necessary to increase the dose. The same dose should be maintained for at least 2 weeks after a dose change, except when immediate dose reduction is required for safety reasons. Neither dose increase from 5 to 20 mg nor dose reduction from 20 to 5 mg will be allowed.

The duration of administration will be 52 weeks. Participants will visit the study site every 2 weeks during the first month of treatment and every 4 weeks thereafter (Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52). Participants will be followed up 4 weeks after the last dose of the study drug, and those who prematurely discontinue the study will also be followed up 4 weeks after the last dose, whenever possible.

Eligibility criteria: Inclusion Criteria:

1. Has completed the double-blind treatment period of the preceding study (CCT-003)
2. Signs and dates a written, informed consent form for this study, different from that for the preceding study (CCT-003).
3. Has CGI-S score improved at least one point at completion of the 8-week double-blind treatment period compared to the Baseline Visit in the preceding study (CCT-003).
4. In the opinion of the investigator, the subject appears to benefit from long-term treatment of Lu AA21004.

Exclusion Criteria:

1. Diagnosed with the following disorder or symptom in the preceding study (CCT-003):

   * Any current psychiatric disorder other than MDD as defined in a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR).
   * Any substance-related disorder (except nicotine and caffeine-related disorders) as defined in the DSM-IV-TR.
   * 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 this study.
2. Is at significant risk of suicide, or had a score ≥5 on Item 10 (suicidal thoughts) of the MADRS or attempted suicides during the preceding study (CCT-003)

Primary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events
timeFrame: 52 Weeks.
measure: Number of Participants With Markedly Abnormal Laboratory Values
timeFrame: Up to week 52.
measure: Significant Change from Baseline in Body Weight
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
measure: Change from Baseline in Vital Signs
timeFrame: 52 Weeks.
measure: Change from Baseline in Electrocardiograms
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
measure: Clinically Significant Change From Baseline in Physical Examination Findings
timeFrame: 52 Weeks.
Secondary outcomes:
measure: Change from Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at each time point
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
measure: Change from Baseline in the Clinical Global Impression Scale-Severity (CGI-S) score at each time point
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
measure: Change from Baseline in the Clinical Global Impression - Improvement (CGI-I) score at each time point
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
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 Director
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.