Clinical trial NCT01179516: Safety and Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
Official title: A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses (10 and 15 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
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-08-11
Enrollment: 469
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 469 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):

* Vortioxetine 10 mg
* Vortioxetine 15 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 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:

* 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.
* The reported duration of the current MDE is at least 3 months.
* Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of 26 or greater at Screening and Baseline Visits.
* Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits.

Exclusion Criteria:

* Has received any investigational compound \<30 days before Screening or 5 half-lives prior to Screening.
* Has received Lu AA21004 in a previous clinical study.
* Has 1 or more the following:

  1. Any current psychiatric disorder other than MDD as defined in the DSM-IV-TR .
  2. Current 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.
  3. Diagnosis of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that had not been in sustained full remission for at least 2 years prior to Screening.
  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.
* The current depressive symptoms of the patient were considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
* Has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening.
* Was currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or planned to initiate such therapy during the study.
* Has a significant risk of suicide according to the investigator's clinical judgment or had a score ≥5 on item 10 (suicidal thoughts) of the MADRS or had made a suicide attempt in the previous 6 months.
* Was required to take excluded medications or it was anticipated that would require treatment with at least 1 of the disallowed concomitant medications during the study.
* Has a clinically significant unstable illness, for example hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, hematological, infectious, dermatological disorder or metabolic disturbance. NOTE: For the purposes of this study, the following conditions were considered unstable due to the potential impact on assessment of MDD response: pain disorder, chronic fatigue syndrome, fibromyalgia, and obstructive sleep apnea.
* Has 1 or more laboratory value outside the normal range, based on the blood or urine samples taken at the Screening Visit, that were considered by the investigator to be clinically significant; or the patient has any of the following values at the Screening Visit:

  1. A serum creatinine value \>1.5 times the upper limits of normal (× ULN).
  2. A total serum total bilirubin value \>1.5 × ULN.
  3. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \>2 × ULN.
* Has a thyroid stimulating hormone value outside the normal range.
* Has clinically significant abnormal vital signs.
* Has an abnormal electrocardiogram.

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: 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
timeFrame: Baseline and Week 8
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Carson
country: United States
state: California
city: Cerritos
country: United States
state: California
city: El Centro
country: United States
state: California
city: Fresno
country: United States
state: California
city: Glendale
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Oakland
country: United States
state: California
city: Oceanside
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Sherman Oaks
country: United States
state: California
city: Stanford
country: United States
state: California
city: Upland
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: Hockessin
country: United States
state: Delaware
city: Fort Walton Beach
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Pompano Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Hoffman Estates
country: United States
state: Illinois
city: Naperville
country: United States
state: Illinois
city: Oak Brook
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Lafayette
country: United States
state: Indiana
city: Newburgh
country: United States
state: Indiana
city: Prarie Ridge
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Baltimore
country: United States
state: Maryland
city: Fall River
country: United States
state: Massachusetts
city: Watertown
country: United States
state: Massachusetts
city: Clinton Township
country: United States
state: Michigan
city: St. Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Nashua
country: United States
state: New Hampshire
city: Albuquerque
country: United States
state: New Mexico
city: Staten Island
country: United States
state: New York
city: Avon Lake
country: United States
state: Ohio
city: Beachwood
country: United States
state: Ohio
city: Canton
country: United States
state: Ohio
city: Garfield Heights
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Salem
country: United States
state: Oregon
city: Allentown
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Lincoln
country: United States
state: Rhode Island
city: Columbia
country: United States
state: South Carolina
city: Franklin
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Desoto
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Lake Jackson
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: The Woodlands
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Roanoke
country: United States
state: Virginia
city: Milwaukee
country: United States
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director, Clinical Science
role: STUDY_DIRECTOR
References:
citation: Mahableshwarkar AR, Jacobsen PL, Serenko M, Chen Y, Trivedi MH. A randomized, double-blind, placebo-controlled study of the efficacy and safety of 2 doses of vortioxetine in adults with major depressive disorder. J Clin Psychiatry. 2015 May;76(5):583-91. doi: 10.4088/JCP.14m09337.