Trial Outcomes & Findings for Study of Vortioxetine (Lu AA21004) in Major Depressive Disorder in Asian Countries (NCT NCT01571453)

NCT ID: NCT01571453

Last Updated: 2014-10-13

Results Overview

Montgomery and Asberg Depression Rating Scale (MADRS) is a ten-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at two-point intervals. The total score of the ten items ranges from 0 to 60. The higher the score, the more severe, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 437 participants
• Primary outcome timeframe: Baseline and Week 8
• Results posted on: 2014-10-13

Participant Flow

In- or outpatients with a primary diagnosis of recurrent of Major Depressive Disorder (MDD) were recruited for this study from China, South Korea, Taiwan, and Thailand.

A Screening Visit was held approximately 7 days prior to group assignment (group assignment was held during the Baseline Visit). Patients who met each of the inclusion criteria at the Screening and Baseline Visits and none of the exclusion criteria at the Screening and/or Baseline Visit were eligible to participate in this study.

Participant milestones

Measure	Vortioxetine Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine Venlafaxine extended release 150 mg/day
Overall Study STARTED	211	226
Overall Study COMPLETED	173	164
Overall Study NOT COMPLETED	38	62

Reasons for withdrawal

Measure	Vortioxetine Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine Venlafaxine extended release 150 mg/day
Overall Study Adverse Event	14	32
Overall Study Lack of Efficacy	8	3
Overall Study Non-compliance	2	4
Overall Study Protocol Violation	1	5
Overall Study Withdrawal of consent	5	13
Overall Study Lost to Follow-up	4	2
Overall Study Administrative or other reason(s)	4	3

Baseline Characteristics

Study of Vortioxetine (Lu AA21004) in Major Depressive Disorder in Asian Countries

Baseline characteristics by cohort

Measure	Vortioxetine n=211 Participants Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine n=226 Participants Venlafaxine extended release: 150 mg/day	Total n=437 Participants Total of all reporting groups
Age, Continuous	39.6 years STANDARD_DEVIATION 12.4 • n=5 Participants	40.7 years STANDARD_DEVIATION 12.3 • n=7 Participants	40.1 years STANDARD_DEVIATION 12.3 • n=5 Participants
Sex: Female, Male Female	123 Participants n=5 Participants	139 Participants n=7 Participants	262 Participants n=5 Participants
Sex: Female, Male Male	88 Participants n=5 Participants	87 Participants n=7 Participants	175 Participants n=5 Participants
MADRS total score	32.3 units on a scale STANDARD_DEVIATION 4.6 • n=5 Participants	32.3 units on a scale STANDARD_DEVIATION 4.5 • n=7 Participants	32.3 units on a scale STANDARD_DEVIATION 4.6 • n=5 Participants
HAM-A total score	20.6 units on a scale STANDARD_DEVIATION 7.3 • n=5 Participants	21.1 units on a scale STANDARD_DEVIATION 7.0 • n=7 Participants	20.9 units on a scale STANDARD_DEVIATION 7.1 • n=5 Participants
CGI-S score	4.8 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	4.9 units on a scale STANDARD_DEVIATION 0.7 • n=7 Participants	4.9 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.

Montgomery and Asberg Depression Rating Scale (MADRS) is a ten-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at two-point intervals. The total score of the ten items ranges from 0 to 60. The higher the score, the more severe, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Outcome measures

Measure	Vortioxetine n=209 Participants Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine n=215 Participants Venlafaxine extended release: 150 mg/day
Change From Baseline in MADRS Total Score at Week 8	-19.36 units on a scale Standard Error 0.70	-18.16 units on a scale Standard Error 0.68

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.

Clinical Global Impression Scale - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher score indicates that the subject is more ill, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Outcome measures

Measure	Vortioxetine n=209 Participants Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine n=215 Participants Venlafaxine extended release: 150 mg/day
Change in CGI-S Score From Baseline to Week 8	-2.26 units on a scale Standard Error 0.09	-2.12 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Week 8

Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.

The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not. Higher score = more affected.

Outcome measures

Measure	Vortioxetine n=209 Participants Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine n=215 Participants Venlafaxine extended release: 150 mg/day
CGI-I Score at Week 8	1.99 units on a scale Standard Error 0.08	2.14 units on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.

Hamilton Anxiety Rating Scale (HAM-A) is a 14-item rating scale designed to assess the global anxiety. Each symptom is rated from 0 (absent) to 4 (maximum severity). The total score of the 14 items ranges from 0 to 56. Higher score indicates greater anxiety, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Outcome measures

Measure	Vortioxetine n=209 Participants Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine n=215 Participants Venlafaxine extended release: 150 mg/day
Change in HAM-A Total Score From Baseline to Week 8	-11.38 units on a scale Standard Error 0.48	-10.56 units on a scale Standard Error 0.47

SECONDARY outcome

Timeframe: Week 8

Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.

Outcome measures

Measure	Vortioxetine n=209 Participants Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine n=215 Participants Venlafaxine extended release: 150 mg/day
MADRS Response at Week 8 (Response Defined as a ≥50% Decrease in the MADRS Total Score From Baseline)	66.5 percentage of patients	61.4 percentage of patients

SECONDARY outcome

Timeframe: Week 8

Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.

Outcome measures

Measure	Vortioxetine n=209 Participants Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine n=215 Participants Venlafaxine extended release: 150 mg/day
Remission at Week 8 (Remission Defined as a MADRS Total Score ≤10)	43.1 percentage of patients	41.4 percentage of patients

SECONDARY outcome

Timeframe: Baseline to Week 12

Outcome measures

Outcome data not reported

Adverse Events

Vortioxetine

Serious events: 2 serious events

Other events: 90 other events

Deaths: 0 deaths

Venlafaxine

Serious events: 8 serious events

Other events: 124 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vortioxetine n=211 participants at risk Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine n=226 participants at risk Venlafaxine extended release: 150 mg/day
Ear and labyrinth disorders Vertigo positional	0.00% 0/211 • Baseline to 12 weeks	0.44% 1/226 • Baseline to 12 weeks
General disorders Asthenia	0.00% 0/211 • Baseline to 12 weeks	0.44% 1/226 • Baseline to 12 weeks
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/211 • Baseline to 12 weeks	0.44% 1/226 • Baseline to 12 weeks
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/211 • Baseline to 12 weeks	0.44% 1/226 • Baseline to 12 weeks
Psychiatric disorders Anxiety	0.00% 0/211 • Baseline to 12 weeks	0.44% 1/226 • Baseline to 12 weeks
Psychiatric disorders Depression	0.47% 1/211 • Baseline to 12 weeks	0.00% 0/226 • Baseline to 12 weeks
Psychiatric disorders Major depression	0.00% 0/211 • Baseline to 12 weeks	0.44% 1/226 • Baseline to 12 weeks
Psychiatric disorders Suicide attempt	0.47% 1/211 • Baseline to 12 weeks	0.88% 2/226 • Baseline to 12 weeks
Reproductive system and breast disorders Varicocele	0.00% 0/211 • Baseline to 12 weeks	0.44% 1/226 • Baseline to 12 weeks

Other adverse events

Measure	Vortioxetine n=211 participants at risk Vortioxetine (Lu AA21004): 10 mg/day	Venlafaxine n=226 participants at risk Venlafaxine extended release: 150 mg/day
Gastrointestinal disorders Constipation	4.3% 9/211 • Baseline to 12 weeks	8.0% 18/226 • Baseline to 12 weeks
Gastrointestinal disorders Dry mouth	5.7% 12/211 • Baseline to 12 weeks	10.6% 24/226 • Baseline to 12 weeks
Gastrointestinal disorders Dyspepsia	5.2% 11/211 • Baseline to 12 weeks	4.0% 9/226 • Baseline to 12 weeks
Gastrointestinal disorders Nausea	24.2% 51/211 • Baseline to 12 weeks	23.5% 53/226 • Baseline to 12 weeks
Injury, poisoning and procedural complications Accidental overdose	4.7% 10/211 • Baseline to 12 weeks	5.3% 12/226 • Baseline to 12 weeks
Metabolism and nutrition disorders Decreased appetite	4.7% 10/211 • Baseline to 12 weeks	10.2% 23/226 • Baseline to 12 weeks
Nervous system disorders Dizziness	8.5% 18/211 • Baseline to 12 weeks	14.2% 32/226 • Baseline to 12 weeks
Nervous system disorders Headache	8.1% 17/211 • Baseline to 12 weeks	7.1% 16/226 • Baseline to 12 weeks
Psychiatric disorders Insomnia	2.4% 5/211 • Baseline to 12 weeks	7.5% 17/226 • Baseline to 12 weeks

Additional Information

Email contact via H. Lundbeck A/S

Study Director

Email: LundbeckClinicalTrials@lundbeck.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place