Clinical trial NCT00735709: Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
Official title: A Randomized, Double-blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy and Safety of 3 Doses of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Keywords: Depression
Depressive Disorder
Mood Disorder
Mental Disorder
Melancholia, Involutional
Paraphrenia, Involutional
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: H. Lundbeck A/S
First posted: 2008-08-15
Enrollment: 560
Sex: ALL
Minimum age (years): 18
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 determine the effectiveness and safety of vortioxetine, once daily (QD), in patients 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 dosages of vortioxetine.

The study enrolled 560 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 1 mg
* Vortioxetine 5 mg
* Vortioxetine 10 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-centre trial was conducted in Europe, Asia, Australia, and South Africa. The overall time to participate in this study was up to 14 weeks. Participants made 7 visits to the clinic, and were contacted by telephone 4 weeks after the last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

* Has a primary diagnosis of major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
* The reported duration of the current major depressive episode is at least 3 months.
* Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥26.
* A male or a female of childbearing potential who is sexually active agrees to use adequate contraception from Screening throughout the duration of the study and for 1 month after the last dose of study medication.

Exclusion Criteria:

* Has 1 or more the following:

  * Any current psychiatric disorder other than major depressive disorder as defined in the DSM-IV-TR.
  * Current or past 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.
  * Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR. (must have negative urine drug screen prior to Baseline).
  * Presence or history of a clinically significant neurological disorder (including epilepsy).
  * Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
* Has a significant risk of suicide according to the investigator's opinion or has a score ≥5 on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale, or has made a suicide attempt in the previous 6 months.
* Currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study.
* Has a clinically significant unstable illness.
* Has previously failed to respond to adequate treatment with selective serotonin reuptake inhibitors and/or serotonin-norepinephrine reuptake inhibitors.
* Has received electroconvulsive therapy within 6 months prior to Screening.
* Has an alanine aminotransferase, aspartate aminotransferase, or total bilirubin level \> 1.5 times the upper limit of normal.
* Has a serum creatinine of \> 1.5 × upper limit of normal.
* Has a previous history of cancer that had been in remission for less than 5 years.
* Has thyroid stimulating hormone value outside the normal range.
* Has an abnormal electrocardiogram.

Primary outcomes:
measure: Change From Baseline in the 24-item Hamilton Depression Scale Total Score At Week 8
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8
timeFrame: Baseline to Week 8
measure: Clinical Global Impression Scale-Global Improvement at Week 8
timeFrame: Baseline to Week 8
measure: Percentage of Responders in HAM-D24 Total Score at Week 8
timeFrame: Baseline and Week 8
measure: Change From Baseline in HAM-D24 Total Score at Week 8 in Participants With Baseline HAM-A Score ≥20
timeFrame: Baseline to Week 8
measure: Percentage of Participants in MADRS Remission at Week 8
timeFrame: Week 8
measure: Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed
timeFrame: Baseline and Weeks 1, 2, 4 and 6
measure: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Other Weeks Assessed
timeFrame: Baseline and Weeks 1, 2 and 6
measure: Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed
timeFrame: Baseline and Weeks 1, 2, 4 and 6
measure: Percentage of Responders in HAM-D24 Total Score at Other Weeks Assessed
timeFrame: Baseline and Weeks 1, 2, 4 and 6
measure: Change From Baseline in HAM-D24 Total Score at Other Weeks Assessed in Participants With a Baseline HAM-A Score ≥20
timeFrame: Baseline and Weeks 1, 2, 4 and 6
measure: Percentage of Participants in MADRS Remission at Other Weeks Assessed
timeFrame: Weeks 1, 2, 4 and 6
measure: Percentage of Participants With a Sustained Response in HAM-D24 Total Score
timeFrame: From Baseline through Week 8
measure: Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score at Each Week
timeFrame: Baseline and Weeks 1, 2, 4, 6, and 8
measure: Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Each Week Assessed
timeFrame: Baseline and Weeks 1, 2, 4, 6, and 8
measure: Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed
timeFrame: Baseline and Weeks 1, 2, 4, 6, and 8
measure: Change From Baseline in Hospital Anxiety and Depression (HAD) Scales at Each Week Assessed
timeFrame: Baseline and Weeks 1, 4, and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Functioning Subscore at All Weeks Assessed
timeFrame: Baseline and Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Physical Subscore at All Weeks Assessed
timeFrame: Baseline and Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Bodily Pain Subscore at All Weeks Assessed
timeFrame: Baseline and Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) General Health Subscore at All Weeks Assessed
timeFrame: Baseline and Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Vitality Subscore at All Weeks Assessed
timeFrame: Baseline and Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Social Functioning Subscore at Other Weeks Assessed
timeFrame: Baseline and Weeks 2 and 4
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Emotional Subscore at All Weeks Assessed
timeFrame: Baseline and Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Mental Health Subscore at All Weeks Assessed
timeFrame: Baseline and Weeks 2, 4 and 8
measure: Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire.
timeFrame: Baseline and Week 8
Other outcomes:
Locations:
city: Elizabeth Vale
country: Australia
city: Southport
country: Australia
city: Litomerice
country: Czech Republic
city: Lnare
country: Czech Republic
city: Prague
country: Czech Republic
city: Praha
country: Czech Republic
city: Bully les Mines
country: France
city: Marseille
country: France
city: Strasbourg
country: France
city: Bochum
country: Germany
city: Chemnitz
country: Germany
city: Dillingen
country: Germany
city: Huettenberg
country: Germany
city: Leipzig
country: Germany
city: Munchen
country: Germany
city: München
country: Germany
city: Nuernberg
country: Germany
city: Osnabrueck
country: Germany
city: Rodgau
country: Germany
city: Westerstede
country: Germany
city: Bucheon-si
country: Korea, Republic of
city: Namdong-gu
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Leipaja
country: Latvia
city: Riga
country: Latvia
city: Sigulda
country: Latvia
city: Strenci
country: Latvia
city: Vilnius
country: Lithuania
city: Kuala Lumpur
country: Malaysia
city: Wildervank
country: Netherlands
city: Białystok
country: Poland
city: Leszno
country: Poland
city: Skórzewo
country: Poland
city: Toruń
country: Poland
city: Tuszyn
country: Poland
city: Moscow
country: Russian Federation
city: Novgorod
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Durban
country: South Africa
city: Noordheuwel
country: South Africa
city: Pretoria
country: South Africa
city: Lin-Yan District
country: Taiwan
city: Dnepropetrovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Lugansk
country: Ukraine
city: Simferopol
country: Ukraine
city: Bath
country: United Kingdom
city: Bolton
country: United Kingdom
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Henigsberg N, Mahableshwarkar AR, Jacobsen P, Chen Y, Thase ME. A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of Lu AA21004 in adults with major depressive disorder. J Clin Psychiatry. 2012 Jul;73(7):953-9. doi: 10.4088/JCP.11m07470.
citation: McIntyre RS, Florea I, Tonnoir B, Loft H, Lam RW, Christensen MC. Efficacy of Vortioxetine on Cognitive Functioning in Working Patients With Major Depressive Disorder. J Clin Psychiatry. 2017 Jan;78(1):115-121. doi: 10.4088/JCP.16m10744.