Clinical trial NCT01255787: Efficacy and Safety Study of Vortioxetine (Lu AA21004) for Treatment of Major Depressive Disorder
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Depressive Disorder, Major
Keywords: Major Depressive Disorder
Depression
Melancholia
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-12-07
Enrollment: 600
Sex: ALL
Minimum age (years): 20
Maximum age (years): 64
Standard ages: 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 and safety of multiple doses of vortioxetine, once daily (QD), in participants with major depressive disorder.

Detailed description: The drug that was tested in this study is called vortioxetine. Vortioxetine is being tested to treat depression in adults who have major depressive disorder (MDD). This study looked at MDD relief in people who took varying doses of vortioxetine.

The study enrolled 600 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):

* Vortioxetine 5 mg
* Vortioxetine 10 mg
* Vortioxetine 20 mg
* Placebo (dummy inactive pill) - this was a capsule that looked like the study drug but had no active ingredient.

All participants were asked to take one capsule at the same time each day throughout the study.

This multi-center trial was conducted in 14 countries in Europe and Asia. The overall time to participate in this study was up to 13 weeks. Participants made weekly visits to the clinic during the first 2 weeks of the 8-week treatment period and then every 2 weeks up to the end of the 8-week treatment period. Participants who completed the 8-week treatment period entered a 2-week discontinuation period to assess potential discontinuation symptoms 1 and 2 weeks after the end of the 8-week treatment period. A safety follow-up contact (visit or phone call) was made 4 weeks after completion of the 8-week double-blind treatment period (2 weeks after the end of the 2-week discontinuation period).

Eligibility criteria: Inclusion Criteria:

1. 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).
2. The reported duration of the current major depressive episode is at least 3 months at the Screening Visit.
3. Has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26 at the Screening and Baseline Visits.
4. Has a Clinical Global Impression Scale-Severity (CGI-S) score ≥4 at the Screening and Baseline Visits.

Exclusion Criteria:

1. 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 participant who exhibits symptoms of anxiety is eligible unless fulfilling 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. Participant 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.
2. The current depressive symptoms of the participant are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
3. Has received electroconvulsive, vagal nerve stimulation, or repetitive transcranial magnetic stimulation therapy within 6 months prior to the Screening Visit.
4. Is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study.
5. 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.

Primary outcomes:
measure: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Percentage of Participants With a MADRS Response at Week 8
timeFrame: Baseline and Week 8
measure: Percentage of Participants in MADRS Remission at Week 8
timeFrame: Week 8
measure: Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8
timeFrame: Week 8
measure: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8
timeFrame: Baseline and Week 8
Other outcomes:
Locations:
city: Split
country: Croatia
city: Zagreb
country: Croatia
city: Helsinki
country: Finland
city: Kuopio
country: Finland
city: Oulu
country: Finland
city: Tampere
country: Finland
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Chemnitz
country: Germany
city: Hannover
country: Germany
city: Leipzig
country: Germany
city: Munchen
country: Germany
city: Nuernberg
country: Germany
city: Schwerin
country: Germany
city: Westerstede
country: Germany
city: Wiesbaden
country: Germany
city: Hong Kong
country: Hong Kong
city: Hyderabad
country: India
state: Andhra Pradesh
city: Ahmedabad
country: India
state: Gujarat
city: Lucknow
country: India
state: Uttar Pradesh
city: Varanasi
country: India
state: Uttar Pradesh
city: Kanpur
country: India
state: UttarPradesh
city: Tokoname-shi
country: Japan
state: Aichi
city: Fukuoka-shi
country: Japan
state: Fukuoka
city: Kitakyushu-shi
country: Japan
state: Fukuoka
city: Omuta-shi
country: Japan
state: Fukuoka
city: Shirakawa-shi
country: Japan
state: Fukushima
city: Sapporo-shi
country: Japan
state: Hokkaido
city: Yokohama-shi
country: Japan
state: Kanagawa
city: Kumamoto-shi
country: Japan
state: Kumamoto
city: Tokyo
country: Japan
city: Sungnam-si
country: Korea, Republic of
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
state: Korea
city: Seoul
country: Korea, Republic of
state: Korea
city: Yangsan-si
country: Korea, Republic of
state: Korea
city: Liepaja
country: Latvia
city: Riga
country: Latvia
city: Sigulda
country: Latvia
city: Johor Bahru
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Makati City
country: Philippines
state: NCR
city: Mandaluyong City
country: Philippines
state: NCR
city: Manila
country: Philippines
state: NCR
city: Quezon City
country: Philippines
state: NCR
city: Bialystok
country: Poland
city: Gorlice
country: Poland
city: Leszno
country: Poland
city: Torun
country: Poland
city: Zuromin
country: Poland
city: Iasi
country: Romania
state: Lasi
city: Targu Mures
country: Romania
state: Mures
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Ekaterinburg
country: Russian Federation
state: Russia
city: Nizhny Novgorod
country: Russian Federation
state: Russia
city: Rostov on Don
country: Russian Federation
state: Russia
city: Saint-Petersburg
country: Russian Federation
state: Russia
city: Smolensk
country: Russian Federation
state: Russia
city: St. Petersburg
country: Russian Federation
state: Russia
city: Stavropol
country: Russian Federation
state: Russia
city: Belgrade
country: Serbia
city: Kragujevac
country: Serbia
city: Senta
country: Serbia
city: Changhua
country: Taiwan
city: Kaohsiung City
country: Taiwan
city: Taipei City
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan Hsien
country: Taiwan
city: Chernigiv region
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Kharkiv,
country: Ukraine
city: Kiev
country: Ukraine
city: Lugansk
country: Ukraine
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Nishimura A, Aritomi Y, Sasai K, Kitagawa T, Mahableshwarkar AR. Randomized, double-blind, placebo-controlled 8-week trial of the efficacy, safety, and tolerability of 5, 10, and 20 mg/day vortioxetine in adults with major depressive disorder. Psychiatry Clin Neurosci. 2018 Feb;72(2):64-72. doi: 10.1111/pcn.12565. Epub 2017 Oct 3.