Clinical trial NCT02371980: Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Depressive Disorder
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-02-26
Enrollment: 1106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time From Randomization to Relapse of Major Depressive Disorder During the First 28 Weeks of the 32-Week Double-Blind Treatment Period
timeFrame: 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 outcomes:
measure: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
timeFrame: Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32
measure: Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed
timeFrame: Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32
measure: Clinical Global Impression Scale-Global Improvement Scale (CGI-I) Score
timeFrame: Week 32
measure: Time From Randomization to Relapse of Major Depressive Disorder During the Entire 32-Week Double-Blind Treatment Period
timeFrame: 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)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: NoesisPharma
state: Arizona
city: Tucson
country: United States
facility: SW Biomedical Research, LLC
state: Arizona
city: Cerritos
country: United States
facility: CNS Research Science, Inc.
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Irvine
country: United States
facility: Irvine Center for Clinical Research, Inc.
state: California
city: Lemon Grove
country: United States
facility: Synergy Clinical Research of Escondido
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Los Angeles
country: United States
facility: Pacific Institute of Medical Research
state: California
city: Pico Rivera
country: United States
facility: CNRI - Los Angeles, LLC
state: California
city: San Diego
country: United States
facility: CNRI - San Diego, LLC
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research, LLC
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: San Gabriel
country: United States
facility: Pasadena Research Institute
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Norwalk
country: United States
facility: Research Center for Clinical Studies, Inc.
state: Connecticut
city: Coral Springs
country: United States
facility: CNS Clinical Research Group
state: Florida
city: Fort Myers
country: United States
facility: Gulfcoast Medical Research Center, LLC
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc.
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Maitland
country: United States
facility: Meridien Research
state: Florida
city: Ocala
country: United States
facility: Sarkis Clinical Trials - Parent
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials, LLC
state: Florida
city: West Palm Beach
country: United States
facility: Janice L. Miller, M.D., PA d/b/a Janus Center for Psychiatric Reseach
state: Florida
city: Atlanta
country: United States
facility: Radiant Research, Inc.
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta, LLC
state: Georgia
city: Arlington Heights
country: United States
facility: Alexian Brothers Center for Psychiatric Research
state: Illinois
city: Chicago
country: United States
facility: Rush St Lukes Presbyterian Medical Center
state: Illinois
city: Libertyville
country: United States
facility: Capstone Clinical Research, Inc.
state: Illinois
city: Indianapolis
country: United States
facility: Goldpoint Clinical Research, LLC
state: Indiana
city: Valparaiso
country: United States
facility: Buynak Clinical Research
state: Indiana
city: Prairie Village
country: United States
facility: Phoenix Medical Research, Inc.
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Pharmasite Research, Inc.
state: Maryland
city: Gaithersburg
country: United States
facility: Potomac Grove Clinical Research Center
state: Maryland
city: Boston
country: United States
facility: Boston Clinical Trials & Medical Research
state: Massachusetts
city: Worcester
country: United States
facility: Univ. of Massachussetts Memorial Health Care Systems
state: Massachusetts
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center PRIME
state: New York
city: Buffalo
country: United States
facility: Erie County Medical Center Corporation
state: New York
city: Cedarhurst
country: United States
facility: Neurobehavioral Research, Inc.
state: New York
city: Jamaica
country: United States
facility: CNS Research Science, Inc.
state: New York
city: New York
country: United States
facility: Village Clinical Research, Inc.
state: New York
city: New York
country: United States
facility: Manhattan Behavioral Medicine, PLLC
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Hickory
country: United States
facility: Clinical Trials of America, Inc
state: North Carolina
city: Beachwood
country: United States
facility: NorthCoast Clinical Trials, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Patient Priority Clinical Sites, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group, Inc.
state: Oklahoma
city: Portland
country: United States
facility: Summit Research Network (Oregon) Inc.
state: Oregon
city: Portland
country: United States
facility: Oregon Center for Clinical Investigations, Inc.
state: Oregon
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Norristown
country: United States
facility: Keystone Clinical Studies, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania School of Medicine
state: Pennsylvania
city: Lincoln
country: United States
facility: Lincoln Research
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center, Inc
state: South Carolina
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Clinical Trials, L.P.
state: Texas
city: Austin
country: United States
facility: BioBehavioral Research of Austin
state: Texas
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, LP
state: Texas
city: Houston
country: United States
facility: Bayou City Research, Ltd.
state: Texas
city: Houston
country: United States
facility: Houston Clinical Trials, LLC
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Murray
country: United States
facility: Radiant Research, Inc.
state: Utah
city: Woodstock
country: United States
facility: Neuropsychiatric Associates
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Everett
country: United States
facility: Eastside Therapeutic Resource
state: Washington
city: Seattle
country: United States
facility: Summit Research Network (Seattle), LLC
state: Washington
city: Spokane
country: United States
facility: Frontier Institute
state: Washington
city: Brown Deer
country: United States
facility: Northbrooke Research Center
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Thase ME, Jacobsen PL, Hanson E, Xu R, Tolkoff M, Murthy NV. Vortioxetine 5, 10, and 20 mg significantly reduces the risk of relapse compared with placebo in patients with remitted major depressive disorder: The RESET study. J Affect Disord. 2022 Apr 15;303:123-130. doi: 10.1016/j.jad.2022.02.002. Epub 2022 Feb 5.