Open-label Safety Extension Study of 2.5, 5 and 10 mg of Vortioxetine (Lu AA21004) in Long-term Treatment of Major Depressive Disorder in Adults

A Long-term, Open-label, Flexible-dose, Extension Study Evaluating the Safety and Tolerability of [Vortioxetine] Lu AA21004 in Patients With Major Depressive Disorder

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00694304

Enrollment

535

Registered

2008-06-10

Start date

2008-05-31

Completion date

2010-04-30

Last updated

2014-04-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder, Long-term, Safety, Open-label

Brief summary

The purpose of the study is to evaluate long-term safety and tolerability of Vortioxetine over a period of 52 weeks in patients with Major Depressive Disorder (MDD) having completed 8-week acute treatment.

Interventions

DRUGVortioxetine (Lu AA21004)

2.5, 5, or 10 mg/day; tablets; orally

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

\- Patients who completed 8-week short-term treatment study for Major Depressive Episode, NCT00635219 / 11984A

Exclusion criteria

* Any current psychiatric disorder other than MDD as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Ed., Text revision (DSM-IV TR) * Female patients of childbearing potential who are not using effective contraception * Use of any psychoactive medication Other protocol-defined inclusion and

Design outcomes

Primary

Measure	Time frame
Number of Patients With Adverse Events (AEs)	Baseline to end of the 4-week safety follow-up period
Percentage of Patients Who Withdrew Due to Intolerance to Treatment	Baseline to Week 52

Secondary

Measure	Time frame	Description
Change From Baseline in HAM-A Total Score After 52 Weeks of Treatment	Baseline and Week 52	The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behaviour at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic, and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total score from 0 to 56. The higher the score, the more severe.
Change From Baseline in CGI-S Score After 52 Weeks of Treatment	Baseline and Week 52	The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating.
Proportion of Responders at Week 52 (Response Defined as a >=50% Decrease in MADRS Total Score)	Week 52	—
Change From Baseline in MADRS Total Score After 52 Weeks of Treatment	Baseline and Week 52	The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe.
Proportion of Patients With a MADRS Total Score >=22 After 52 Weeks of Treatment	Baseline and Week 52	—
Change From Baseline in SDS Total Score After 52 Weeks of Treatment	Baseline and Week 52	The Sheehan Disability Scale (SDS) comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). The higher the score, the more severe.
Proportion of Remitters at Week 52 (Remission Defined as a MADRS Total Score <=10)	Week 52	—
Change From Baseline in HAM-D-24 Total Score After 52 Weeks of Treatment	Baseline and Week 52	The Hamilton Depression Scale - 24 Items (HAM-D-24) measures depression severity. Items are rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score range of 0 to 76. The higher the score, the more severe.

Participant flow

Recruitment details

Patients eligible to participate in Study 11984B were patients who had completed lead-in Study NCT00635219 / 11984A immediately prior to inclusion into Study 11984B.

Pre-assignment details

The study consisted of a 52-week open-label period and a 4-week Safety Follow-up Period.

Participants by arm

Arm	Count
Vortioxetine 2.5, 5, or 10 mg/Day tablets; orally	535
Total	535

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Administrative or Other Reasons	32
Overall Study	Adverse Event	42
Overall Study	Lack of Efficacy	35
Overall Study	Lost to Follow-up	15
Overall Study	Non-compliance With Study Product	16
Overall Study	Protocol Violation	6
Overall Study	Withdrawal of Consent	61

Baseline characteristics

Characteristic	Vortioxetine 2.5, 5, or 10 mg/Day
Age, Continuous	45.7 years STANDARD_DEVIATION 12.3
CGI-S	2.7 units on a scale STANDARD_DEVIATION 1.2
HAM-A	11.0 units on a scale STANDARD_DEVIATION 7.2
HAM-D-24	13.4 units on a scale STANDARD_DEVIATION 8.7
MADRS	13.5 units on a scale STANDARD_DEVIATION 8.7
SDS	12.42 units on a scale STANDARD_DEVIATION 8.13
Sex: Female, Male Female	366 Participants
Sex: Female, Male Male	169 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	256 / 535
serious Total, serious adverse events	18 / 535

Outcome results

Primary

Number of Patients With Adverse Events (AEs)

Time frame: Baseline to end of the 4-week safety follow-up period

Population: APTS

Arm	Measure	Group	Value (NUMBER)
Vortioxetine 2.5, 5, or 10 mg/Day	Number of Patients With Adverse Events (AEs)	Patients With AEs	391 participants
Vortioxetine 2.5, 5, or 10 mg/Day	Number of Patients With Adverse Events (AEs)	Patients With SAEs	18 participants
Vortioxetine 2.5, 5, or 10 mg/Day	Number of Patients With Adverse Events (AEs)	Patients With AEs Leading to Withdrawal	42 participants

Primary

Percentage of Patients Who Withdrew Due to Intolerance to Treatment

Time frame: Baseline to Week 52

Population: APTS

Arm	Measure	Value (NUMBER)
Vortioxetine 2.5, 5, or 10 mg/Day	Percentage of Patients Who Withdrew Due to Intolerance to Treatment	7.7 percentage of patients

Secondary

Change From Baseline in CGI-S Score After 52 Weeks of Treatment

The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating.