Clinical trial NCT01153009: Safety and Efficacy of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
Official title: A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Duloxetine-Referenced, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses (15 and 20 mg) of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depressive Disorder, Major
Keywords: Major Depressive Disorder
Depression
Melancholia
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-06-29
Enrollment: 614
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 evaluate the efficacy, safety and tolerability of vortioxetine, once daily (QD), compared with placebo in adults 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 614 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 15 mg
* Vortioxetine 20 mg
* Duloxetine 60 mg
* Placebo (dummy inactive capsule) - 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 the United States. The overall time to participate in this study was up to 13 weeks. Participants made 9 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:

1. Man or a woman who suffers from a major depressive episode (MDE) recurrent as the primary diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.3x) as confirmed by the Structured Clinical Interview for DSM Disorders (SCID).
2. The reported duration of the current MDE is at least 3 months.
3. Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of 26 or greater at Screening and Baseline Visits.
4. Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits.

Exclusion Criteria:

1. Has previously participated in a Lu AA21004 clinical study.
2. Has 1 or more the following:

   1. Any current psychiatric disorder other than major depressive disorder (MDD) as defined in the DSM-IV-TR (as assessed by the SCID).
   2. 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.
   3. Diagnosis of any substance abuse or dependence (except nicotine and caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least 2 years prior to screening (subject must also have negative urine drug screen prior to Baseline).
   4. Presence or history of a clinically significant neurological disorder (including epilepsy).
   5. Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
   6. Any Axis II disorder that might compromise the study.
3. The current depressive symptoms are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each. Has 1 or more laboratory values outside the normal range, based on the blood or urine samples taken at the Screening Visit, that are considered by the investigator to be clinically significant.
4. Has a thyroid stimulating hormone value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator.
5. Has clinically significant abnormal vital signs as determined by the investigator.
6. Has an abnormal electrocardiogram as determined by the central reader and confirmed as clinically significant by the investigator.
7. Has an alanine aminotransferase, aspartate aminotransferase or total bilirubin level greater than 1.5 times the upper limits of normal.
8. Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion does not include those patients with basal cell or Stage I squamous cell carcinoma of the skin.
9. Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.
10. Has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.
11. Has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. The following are also considered unstable due to the potential impact on assessment of MDD response: pain disorder, chronic fatigue syndrome, fibromyalgia, and obstructive sleep apnea.
12. Has a significant risk of suicide according to the investigator's opinion or has a score greater than or equal to 5 on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale or has made a suicide attempt in the previous 6 months.

Primary outcomes:
measure: Change From Baseline in the 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: Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8
timeFrame: Week 8
measure: Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥20
timeFrame: Baseline and Week 8
measure: Percentage of Participants in MADRS Remission 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: Beverly Hills
country: United States
state: California
city: Chino
country: United States
state: California
city: Garden Grove
country: United States
state: California
city: Irvine
country: United States
state: California
city: Los Alamitos
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Pico Rivera
country: United States
state: California
city: San Diego
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Norwalk
country: United States
state: Connecticut
city: Boca Raton
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Gainesville
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Lauderhill
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Libertyville
country: United States
state: Illinois
city: Oakbrook Ter
country: United States
state: Illinois
city: Valparaiso
country: United States
state: Indiana
city: Shreveport
country: United States
state: Louisiana
city: Boston
country: United States
state: Massachusetts
city: Weymouth
country: United States
state: Massachusetts
city: Rochester Hills
country: United States
state: Michigan
city: Flowood
country: United States
state: Mississippi
city: Toms River
country: United States
state: New Jersey
city: Cedarhurst
country: United States
state: New York
city: Fresh Meadows
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Staten Island
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Allentown
country: United States
state: Pennsylvania
city: Media
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: North Charleston
country: United States
state: South Carolina
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Orem
country: United States
state: Utah
city: Woodstock
country: United States
state: Vermont
city: Richmond
country: United States
state: Virginia
city: Middleton
country: United States
state: Wisconsin
city: Waukesha
country: United States
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director, Clinical Science
role: STUDY_DIRECTOR
References:
citation: Christensen MC, Florea I, Loft H, McIntyre RS. Efficacy of vortioxetine in patients with major depressive disorder reporting childhood or recent trauma. J Affect Disord. 2020 Feb 15;263:258-266. doi: 10.1016/j.jad.2019.11.074. Epub 2019 Nov 13.
citation: Mahableshwarkar AR, Jacobsen PL, Chen Y, Serenko M, Trivedi MH. A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD. Psychopharmacology (Berl). 2015 Jun;232(12):2061-70. doi: 10.1007/s00213-014-3839-0. Epub 2015 Jan 11.