Clinical trial NCT00672958: Efficacy and Safety of Vortioxetine (Lu AA21004) in Treating Adults With Major Depressive Disorder
Official title: A Randomized, Double-blind, Parallel-group, Placebo-controlled, Fixed-dose Study Comparing the Efficacy and Safety of Lu AA21004 Versus Placebo in Acute Treatment of Adults With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder
Depression
Drug Therapy
Major Depressive Episode
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: H. Lundbeck A/S
First posted: 2008-05-06
Enrollment: 600
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 efficacy and safety of once daily vortioxetine (Lu AA21004) 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 vortioxetine.

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

* Vortioxetine 5 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 the United States. The overall time to participate in this study was approximately 94 days. Participants made 8 visits to the clinic, and were contacted by telephone 1 week, 2 weeks, and 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) as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, 4th 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 total score greater than or equal to 30.
* Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

Exclusion Criteria:

* Has received any investigational compound less than 30 days before Screening or 5 half-lives prior to Screening, whichever is longer.
* Has received Lu AA21004 in a previous clinical study.
* Has 1 or more the following:

  * Any current psychiatric disorder other than major depressive disorder as defined in the DSM-IV-TR (as assessed by the Mini International Neuropsychiatric Interview)
  * 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.
  * Presence or history of a clinically significant neurological disorder (including epilepsy).
  * Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
  * Any Axis II disorder that might compromise the study.
* Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

  * Narcotic analgesics
  * Nonsteroidal anti-inflammatory drugs
  * Rifampin
  * Macrolide antibiotics
  * Hormones (only thyroid hormone replacement, contraceptives \[oral, patch\], estrogen and progesterone replacement therapy are allowed in chronic use)
  * Hypoglycemic agents (chronic use is allowed)
  * Insulin (chronic use is allowed)
  * Systemic steroids
  * Quinidine
  * Antineoplastics
  * Antiobesity agents
* 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.
* 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 received electroconvulsive therapy within 6 months prior to Screening.
* Is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy 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, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance.
* Has an alanine aminotransferase, aspartate aminotransferase or total bilirubin level greater than 1.5 times the upper limits of normal.
* Has a serum creatinine greater than 1.5 times the upper limits of normal.
* 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 basal cell or Stage I squamous cell carcinoma of the skin.
* Has clinically significant abnormal vital signs as determined by the investigator.
* Has an abnormal electrocardiogram determined by the central reader and confirmed as clinically significant by the investigator.
* 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.
* Has a thyroid stimulating hormone value outside the normal range at Screening Visit that is determined to be clinically significant by the investigator.
* Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.
* Has previously enrolled in this study.

Primary outcomes:
measure: Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 6
timeFrame: Baseline and Week 6
measure: Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed
timeFrame: Baseline and Weeks 1, 2, 3, 4 and 5
Secondary outcomes:
measure: Percentage of Responders in HAM-D24 Total Score by Study Visit
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5 and 6.
measure: Percentage of Participants in MADRS Remission at Week 6
timeFrame: Week 6
measure: Percentage of Participants With a Sustained Response in HAM-D24
timeFrame: Baseline to Week 6
measure: Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5 and 6.
measure: Change From Baseline in Hamilton Anxiety Scale (HAM-A)
timeFrame: Baseline and Weeks 1, 2, 4 and 6.
measure: Change From Baseline in Clinical Global Impression Scale-Severity of Illness
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5 and 6.
measure: Clinical Global Impression Scale-Global Improvement Scale
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5 and 6.
measure: Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S)
timeFrame: Baseline and Weeks 1, 4 and 6.
measure: Change From Baseline in 36-item Short-form Health Survey (SF-36) at Week 6
timeFrame: Baseline and Week 6
measure: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 6
timeFrame: Baseline and Week 6
measure: Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire
timeFrame: Baseline and Week 6
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Cerritos
country: United States
state: California
city: Encino
country: United States
state: California
city: Fresno
country: United States
state: California
city: San Diego
country: United States
state: California
city: Farmington
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: North Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Hoffman Estate
country: United States
state: Illinois
city: Lafayette
country: United States
state: Indiana
city: Valparaiso
country: United States
state: Indiana
city: Shreveport
country: United States
state: Louisiana
city: St. Paul
country: United States
state: Minnesota
city: Florissant
country: United States
state: Missouri
city: St. Charles
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Rochester
country: United States
state: New York
city: Dayton
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Lincoln
country: United States
state: Rhode Island
city: North Charleston
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Lake Jackson
country: United States
state: Texas
city: Wichita Falls
country: United States
state: Texas
city: Brown Deer
country: United States
state: Wisconsin
city: Middleton
country: United States
state: Wisconsin
city: Hull
country: Canada
state: Quebec
city: Mexico, D.F.
country: Mexico
city: San Luis Potosi
country: Mexico
Study officials:
affiliation: Takeda
name: Medical Director, Clinical Science
role: STUDY_DIRECTOR
References:
citation: Jain R, Mahableshwarkar AR, Jacobsen PL, Chen Y, Thase ME. A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and tolerability of 5 mg vortioxetine in adults with major depressive disorder. Int J Neuropsychopharmacol. 2013 Mar;16(2):313-21. doi: 10.1017/S1461145712000727. Epub 2012 Sep 11.