Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD)

Major Depressive Disorder Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 4, Relapse Prevention Study Evaluating the Efficacy and Safety of Vortioxetine (5, 10 and 20 mg) in Adults With Major Depressive Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02371980
• Other study ID #: LuAA21004_402
• Secondary ID: U1111-1161-4956
• Status: Completed
• Phase: Phase 4
• Start date: February 10, 2015
• Est. completion date: April 25, 2019

Study information

• Verified date: December 2020
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of vortioxetine (5, 10, and 20 mg) versus placebo during the first 28 weeks of the 32-week double-blind treatment period in the prevention of relapse in participants with MDD who responded to acute treatment with vortioxetine 10 mg.

Description:

The drug being tested in this study is called vortioxetine. Vortioxetine is being tested for the prevention of relapse in adults with major depressive disorder (MDD) who respond to daily treatment with vortioxetine. This study will look at relapse rates of MDD in people who take vortioxetine. The study will enroll approximately 1100 participants. All participants will receive vortioxetine 10 mg open-label for the first 16 weeks of the study. Participants who meet the appropriate MDD response criteria from the Week 8 Visit through Week 16 Visit will be eligible for randomization into the double-blind treatment period. Participants will be randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): - Vortioxetine 5 mg - Vortioxetine 10 mg - Vortioxetine 20 mg - Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient All participants will be asked to take one capsule at the same time each day throughout the study. This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 55 weeks. Participants will make 19 visits to the clinic, and will be contacted by telephone 4 weeks after last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1106
• Est. completion date: April 25, 2019
• Est. primary completion date: March 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

3. Suffers from recurrent major depressive disorder (MDD) as the primary diagnosis according to Diagnostic & Statistical Manual of Mental Disorders, 4th Edition - Text Revision (DSM-IV-TR) criteria (classification code 296.3x), and the current episode is confirmed by the Mini International Neuropsychiatric Interview (MINI).

4. Reported duration of the current episode is =8 weeks and =18months.

5. Had at least 2 other major depressive episodes (MDEs) before the current episode.

6. Has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score =26 at the Screening and Baseline I visits.

7. Is a man or woman aged 18 to 75 years, inclusive.

8. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study and for 30 days after the last dose.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to screening or 5 half-lives prior to screening, whichever is longer.

2. Has previously or is currently participating in this study.

3. Has participated in 2 or more clinical studies in the year prior to screening, or has participated in a clinical trial for a psychiatric condition that is exclusionary per this protocol.

4. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

5. Has one or more of the following:

1. Any current psychiatric disorder which is the primary focus of treatment other than MDD as defined in the DSM-IV-TR, and assessed by the MINI.

2. Current or history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder, including schizoaffective disorder, major depression with psychotic features, bipolar depression with psychotic features, obsessive compulsive disorder (OCD), mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.

3. Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in full and sustained remission for at least 3 months from the day of screening (Participant must also have negative urine drug screen at Screening and Baseline I.)

4. Presence or history of a clinically significant neurological disorder (including epilepsy) as determined by the investigator.

5. Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).

6. Any Axis II disorder as defined by DSM-IV-TR that might compromise the study.

6. The current depressive symptoms of the participant are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.

7. Has a history of lack of response to previous adequate treatment with vortioxetine for any MDD episode with adequate treatment considered to be known dose of vortioxetine in the approved recommended dose range for at least 6 weeks duration.

8. Has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening.

9. Has started receiving formal cognitive or behavioral therapy, systematic psychotherapy within 30 days from screening or plans to initiate such therapy during the study (supportive therapy, marital therapy and bereavement counseling are allowed).

10. Has a significant risk of suicide according to the investigator's clinical judgment or has a score =5 on item 10 (suicidal thoughts) of the MADRS or has made a suicide attempt in the previous 6 months.

11. Is required to take excluded medications or it is anticipated that the participant will require treatment with at least 1 of the disallowed concomitant medications during the study.

12. Has a clinically significant unstable illness, for example hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, hematological, infectious, dermatological disorder or metabolic disturbance. Note: For the purposes of this protocol fibromyalgia, obstructive sleep apnea, chronic pain diagnosis, and morbid obesity (BMI of > 40) are considered unstable due to the potential impact on assessment of the primary endpoint.

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

14. Has 1 or more laboratory value 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; or the participant has any of the following values at the

Screening Visit:

1. A serum creatinine value >1.5 times the upper limits of normal (ULN).

2. A serum total bilirubin value >1.5 xULN.

3. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2 xULN.

15. Has glycosylated hemoglobin (HbA1C) =7% at screening and no prior diagnosis of diabetes and/or treatment for diabetes. NOTE: Participants with known stable diabetes are not excluded.

16. Has a thyroid stimulating hormone (TSH) value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator. NOTE: Free T4 will be checked if TSH is out of range. If free T4 is abnormal the participant will be excluded.

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

18. Has an abnormal electrocardiogram (ECG) as determined by the central reader and confirmed as clinically significant by the investigator.

19. Is positive for Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, or has a history of human immunodeficiency virus (HIV) infection.

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

21. The participant, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason.

22. Has a history of hypersensitivity or allergies to vortioxetine.

23. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.

24. The participant is considered to be treatment resistant, eg, the participant has not responded to adequate monotherapy treatments of at least 6 weeks' duration, or has only responded to combination or augmentation therapy.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Vortioxetine
Vortioxetine capsules
• Placebo
Vortioxetine placebo-matching capsules

Locations

Country	Name	City	State
United States	Alexian Brothers Center for Psychiatric Research	Arlington Heights	Illinois
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Radiant Research, Inc.	Atlanta	Georgia
United States	BioBehavioral Research of Austin	Austin	Texas
United States	FutureSearch Clinical Trials, L.P.	Austin	Texas
United States	Pharmasite Research, Inc.	Baltimore	Maryland
United States	NorthCoast Clinical Trials, Inc.	Beachwood	Ohio
United States	Hassman Research Institute	Berlin	New Jersey
United States	Boston Clinical Trials & Medical Research	Boston	Massachusetts
United States	Montefiore Medical Center PRIME	Bronx	New York
United States	Northbrooke Research Center	Brown Deer	Wisconsin
United States	Erie County Medical Center Corporation	Buffalo	New York
United States	Neurobehavioral Research, Inc.	Cedarhurst	New York
United States	CNS Research Science, Inc.	Cerritos	California
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Rush St Lukes Presbyterian Medical Center	Chicago	Illinois
United States	Patient Priority Clinical Sites, LLC	Cincinnati	Ohio
United States	CNS Clinical Research Group	Coral Springs	Florida
United States	FutureSearch Trials of Dallas, LP	Dallas	Texas
United States	iResearch Atlanta, LLC	Decatur	Georgia
United States	Duke University Medical Center	Durham	North Carolina
United States	Eastside Therapeutic Resource	Everett	Washington
United States	Gulfcoast Medical Research Center, LLC	Fort Myers	Florida
United States	Potomac Grove Clinical Research Center	Gaithersburg	Maryland
United States	Collaborative Neuroscience Network, LLC	Garden Grove	California
United States	MD Clinical	Hallandale Beach	Florida
United States	Indago Research & Health Center, Inc.	Hialeah	Florida
United States	Clinical Trials of America, Inc	Hickory	North Carolina
United States	Bayou City Research, Ltd.	Houston	Texas
United States	Houston Clinical Trials, LLC	Houston	Texas
United States	Goldpoint Clinical Research, LLC	Indianapolis	Indiana
United States	Irvine Center for Clinical Research, Inc.	Irvine	California
United States	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida
United States	CNS Research Science, Inc.	Jamaica	New York
United States	Lake Charles Clinical Trials, LLC	Lake Charles	Louisiana
United States	Altea Research Institute	Las Vegas	Nevada
United States	Synergy Clinical Research of Escondido	Lemon Grove	California
United States	Capstone Clinical Research, Inc.	Libertyville	Illinois
United States	Lincoln Research	Lincoln	Rhode Island
United States	Pharmacology Research Institute	Los Alamitos	California
United States	Pacific Institute of Medical Research	Los Angeles	California
United States	Meridien Research	Maitland	Florida
United States	Suburban Research Associates	Media	Pennsylvania
United States	Clinical Neuroscience Solutions, Inc.	Memphis	Tennessee
United States	Coastal Carolina Research Center, Inc	Mount Pleasant	South Carolina
United States	Radiant Research, Inc.	Murray	Utah
United States	Manhattan Behavioral Medicine, PLLC	New York	New York
United States	Village Clinical Research, Inc.	New York	New York
United States	Keystone Clinical Studies, LLC	Norristown	Pennsylvania
United States	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut
United States	Sarkis Clinical Trials - Parent	Ocala	Florida
United States	Cutting Edge Research Group, Inc.	Oklahoma City	Oklahoma
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Clinical Neuroscience Solutions, Inc.	Orlando	Florida
United States	University of Pennsylvania School of Medicine	Philadelphia	Pennsylvania
United States	NoesisPharma	Phoenix	Arizona
United States	CNRI - Los Angeles, LLC	Pico Rivera	California
United States	Oregon Center for Clinical Investigations, Inc.	Portland	Oregon
United States	Summit Research Network (Oregon) Inc.	Portland	Oregon
United States	Phoenix Medical Research, Inc.	Prairie Village	Kansas
United States	Pillar Clinical Research, LLC	Richardson	Texas
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Artemis Institute for Clinical Research, LLC	San Diego	California
United States	CNRI - San Diego, LLC	San Diego	California
United States	University of California San Diego Medical Center	San Diego	California
United States	Pasadena Research Institute	San Gabriel	California
United States	Summit Research Network (Seattle), LLC	Seattle	Washington
United States	Frontier Institute	Spokane	Washington
United States	Stedman Clinical Trials, LLC	Tampa	Florida
United States	Collaborative Neuroscience Network, LLC	Torrance	California
United States	SW Biomedical Research, LLC	Tucson	Arizona
United States	Buynak Clinical Research	Valparaiso	Indiana
United States	Janice L. Miller, M.D., PA d/b/a Janus Center for Psychiatric Reseach	West Palm Beach	Florida
United States	Heartland Research Associates, LLC	Wichita	Kansas
United States	Neuropsychiatric Associates	Woodstock	Vermont
United States	Univ. of Massachussetts Memorial Health Care Systems	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time From Randomization to Relapse of Major Depressive Disorder During the First 28 Weeks of the 32-Week Double-Blind Treatment Period	Relapse was defined as either 1) MADRS Score =22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored at date of withdrawal or date of Week 28 visit, whichever was earliest. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The inter-quartile range (IQR) was 25th percentile to 75th percentile.	From date of double-blind randomization (Week 16) up to relapse or first 28 weeks of Double-blind Period which occurs first (Up to Week 44)
Secondary	Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score	MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher score indicates greater severity of symptoms. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. Mixed model for repeated measures (MMRM) was used for analyses.	Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32
Secondary	Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed	The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participant who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness on the following scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=extremely ill. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. MMRM was used for analyses.	Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32
Secondary	Clinical Global Impression Scale-Global Improvement Scale (CGI-I) Score	The CGI-I scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.	Week 32
Secondary	Time From Randomization to Relapse of Major Depressive Disorder During the Entire 32-Week Double-Blind Treatment Period	Relapse was defined as either 1) MADRS Score =22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The IQR was 25th percentile to 75th percentile.	From date of double-blind randomization (Week 16) up to relapse or 32 weeks of Double-blind Period which occurs first (Up to Week 44)