Efficacy and Safety Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder

Phase 3

Completed

• Conditions: Depressive Disorder, Major
• Interventions: Drug: Placebo; Drug: Vortioxetine

• Registration Number: NCT01163266
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to evaluate the efficacy 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 462 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 20 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.

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-07-14
• Study First Submitted QC: 2010-07-14
• Study First Posted: 2010-07-15
• Primary Completion: 2012-01
• Study Completion: 2012-01
• Status Verified: 2013-10
• Results First Submitted: 2013-10-25
• Results First Submitted QC: 2013-10-25
• Last Update Submitted: 2013-10-25
• Results First Posted: 2013-12-18
• Last Update Posted: 2013-12-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 462

Inclusion Criteria

• Suffers from a major depressive episode recurrent as the primary diagnosis according to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
• 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 previously participated in a Lu AA21004 clinical study.

• Has 1 or more the following:

  • Any current psychiatric disorder other than Major Depressive Disorder as defined in the DSM-IV
  • Current or past history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder defined in the DSM-IV-TR.
  • Diagnosis of alcohol or other substance disorder (except nicotine and caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least years prior to screening (participant must also have negative urine drug screen prior to Baseline).
  • Presence or history of a clinically significant neurological disorder (including epilepsy)
  • Neurodegenerative disorder.
  • Any Axis II disorder that might compromise the study.

• Has a thyroid stimulating hormone value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator.

• Has clinically significant abnormal vital signs as determined by the investigator.

• Has an abnormal Electrocardiogram.

• Has an alanine aminotransferase, aspartate aminotransferase or total bilirubin level 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.

• Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.

• Has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.

• 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. For the purposes of this protocol the following conditions are considered unstable due to the potential impact on assessment of MDD response: pain disorder, chronic fatigue syndrome, fibromyalgia, and obstructive sleep apnea.

• Has a significant risk of suicide according to the investigator's opinion.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo-matching capsules, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg	Vortioxetine	Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Vortioxetine 20 mg	Vortioxetine	Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score	Baseline and Week 8	The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) analysis of covariance (ANCOVA) with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With a MADRS Response at Week 8	Baseline and Week 8	Response is defined as a participant with a ≥50% decrease in Montgomery Åsberg Depression Rating Scale (MADRS) total score from Baseline. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
Mean Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 8	Week 8	The Clinical Global Impression-Global Improvement scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline Clinical Global Impression Scale-Severity of Illness Scale (CGI-S) score-by-week as fixed effects.
Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥20	Baseline and Week 8	The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. LS means are from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.; The HAM-A is a 14 item rating scale to quantify anxiety severity rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56, where lower scores indicate mild severity.
Percentage of Participants in MADRS Remission at Week 8	Week 8	Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8	Baseline and Week 8	The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. LS means were from mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline SDS total score-by-week as fixed effects.