A Study of Vortioxetine (Lu AA21004) in Comparison to Agomelatine in Adults Suffering From Major Depression With Inadequate Response to Previous Medication (REVIVE)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

H. Lundbeck A/S

ClinicalTrials.gov Identifier:

NCT01488071

First received: November 29, 2011

Last updated: February 11, 2014

Last verified: February 2014

History of Changes

Results First Received: December 19, 2013

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Major Depressive Disorder
Interventions:	Drug: Vortioxetine (Lu AA21004) Drug: Agomelatine

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
In- or outpatients who had been treated with antidepressant selective serotonin reuptake inhibitor (SSRI) or selective noradrenaline reuptake inhibitor (SNRI) monotherapy that was prescribed to treat a single episode of Major Depressive Disorder (MDD) or recurrent MDD.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study will consist of a screening period of 4 to 10 days before the Baseline Visit, followed by a 12-week treatment period with vortioxetine or agomelatine. A safety follow-up will be done approximately 4 weeks after the Completion/Withdrawal Visit.

Reporting Groups

	Description
Vortioxetine 10 mg or 20 mg	encapsulated tablets, daily, orally
Agomelatine 25 mg or 50 mg	encapsulated tablets, daily, orally

Participant Flow: Overall Study

	Vortioxetine 10 mg or 20 mg	Agomelatine 25 mg or 50 mg
STARTED	253 ^[1]	242 ^[2]
COMPLETED	200	179
NOT COMPLETED	53	63
Adverse Event	15	23
Lack of Efficacy	11	17
Non-compliance with study drug	2	0
Protocol Violation	5	7
Withdrawal of Consent	14	12
Lost to Follow-up	1	0
Administrative or Other Reason(s)	5	4

[1]	all-patients-treated set (APTS)
[2]	APTS

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Age and Gender: All-patients-treated set (APTS) – all patients in the APRS who took at least one dose of investigational medicinal product (IMP). Study Specific Characteristics: Full-analysis set (FAS) - all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Age and Gender: All-patients-treated set (APTS) – all patients in the APRS who took at least one dose of investigational medicinal product (IMP).

Study Specific Characteristics: Full-analysis set (FAS) - all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.

Reporting Groups

	Description
Vortioxetine 10 mg or 20 mg	encapsulated tablets, daily, orally
Agomelatine 25 mg or 50 mg	encapsulated tablets, daily, orally
Total	Total of all reporting groups

Baseline Measures

	Vortioxetine 10 mg or 20 mg	Agomelatine 25 mg or 50 mg	Total
Number of Participants [units: participants]	253	242	495
Age [units: years] Mean ± Standard Deviation	47.0 ± 12.4	45.6 ± 12.4	46.3 ± 12.4
Gender [units: participants]
Female	195	175	370
Male	58	67	125
MADRS: Baseline Total Score ^[1] [units: units on a scale] Mean ± Standard Deviation	29.1 ± 4.4	28.7 ± 4.0	28.9 ± 4.2
HAM-A: Baseline Total Score ^[2] [units: units on a scale] Mean ± Standard Deviation	21.6 ± 6.3	21.4 ± 6.2	21.5 ± 6.2
CGI-S Baseline Severity Score ^[3] [units: units on a scale] Mean ± Standard Deviation	4.4 ± 0.6	4.4 ± 0.6	4.4 ± 0.6
SDS Total Baseline Score ^[4] [units: units on a scale] Mean ± Standard Deviation	19.2 ± 5.3	19.3 ± 5.2	19.3 ± 5.3

[1]	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 - 60. The higher the score, the more severe.
[2]	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; higher score indicates greater anxiety.
[3]	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. Higher score indicates that the patient is more ill.
[4]	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.

Outcome Measures

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1. Primary:

Change From Baseline in MADRS Total Score at Week 8 [ Time Frame: Baseline and Week 8 ]

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2. Secondary:

Change From Baseline in MADRS Total Score at Week 12 [ Time Frame: Baseline and Week 12 ]

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3. Secondary:

Change From Baseline in HAM-A Total Score at Week 8 [ Time Frame: Baseline and Week 8 ]

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4. Secondary:

Change From Baseline in HAM-A Total Score at Week 12 [ Time Frame: Baseline and Week 12 ]

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5. Secondary:

Change From Baseline in CGI-S Score at Week 8 [ Time Frame: Baseline and Week 8 ]

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6. Secondary:

Change From Baseline in CGI-S Score at Week 12 [ Time Frame: Baseline and Week 12 ]

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7. Secondary:

Change in Clinical Status Using CGI-I Score at Week 8 [ Time Frame: Week 8 ]

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8. Secondary:

Change in Clinical Status Using CGI-I Score at Week 12 [ Time Frame: Week 12 ]

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9. Secondary:

Proportion of Patients Who Respond at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline) [ Time Frame: Baseline and Week 8 ]

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10. Secondary:

Proportion of Patients Who Respond at Week 12 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline) [ Time Frame: Baseline and Week 12 ]

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11. Secondary:

Proportion of Patients Who Are in Remission at Week 8 (Remission is Defined as a MADRS Total Score <=10) [ Time Frame: Week 8 ]

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12. Secondary:

Proportion of Patients Who Are in Remission at Week 12 (Remission is Defined as a MADRS Total Score <=10) [ Time Frame: Week 12 ]

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13. Secondary:

Change From Baseline in SDS Total Score at Week 8 [ Time Frame: Baseline and Week 8 ]

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14. Secondary:

Change From Baseline in SDS Total Score at Week 12 [ Time Frame: Baseline and Week 12 ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The results of this study will be published. Authors of the primary publication based on this study must fulfil the criteria defined by the International Committee of Medical Journal Editors (ICMJE). The primary publication must be published before any secondary publications are submitted for publication.

Results Point of Contact:

Name/Title: H. Lundbeck A/S
Organization: H. Lundbeck A/S
phone: +45 36301311
e-mail: LundbeckClinicalTrials@lundbeck.com

No publications provided by H. Lundbeck A/S

Publications automatically indexed to this study:

Montgomery SA, Nielsen RZ, Poulsen LH, Häggström L. A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine. Hum Psychopharmacol. 2014 Sep;29(5):470-82.

Responsible Party:	H. Lundbeck A/S
ClinicalTrials.gov Identifier:	NCT01488071 History of Changes
Other Study ID Numbers:	14178A, 2011-002362-21
Study First Received:	November 29, 2011
Results First Received:	December 19, 2013
Last Updated:	February 11, 2014
Health Authority:	Austria: Austrian Medicines and Medical Devices Agency Belgium: Federal Agency for Medicinal Products and Health Products Bulgaria: Bulgarian Drug Agency Czech Republic: State Institute for Drug Control Estonia: The State Agency of Medicine Germany: Federal Institute for Drugs and Medical Devices Italy: The Italian Medicines Agency Lithuania: State Medicine Control Agency - Ministry of Health Poland: National Institute of Medicines Romania: National Agency for Medicines and Medical Devices Russia: FSI Scientific Center of Expertise of Medical Application Spain: Spanish Agency of Medicines Sweden: Medical Products Agency United Kingdom: Medicines and Healthcare Products Regulatory Agency

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