Levomilnacipran ER vs. Adjunctive Quetiapine for Adults With Inadequate Relief With SSRIs in MDD

NCT02720198 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: Pro00064983
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study's primary objective is to compare the efficacy and tolerability of switching patients with inadequate relief on generic SSRIs to levomilnacipran versus adding a new treatment (quetiapine) to the participants' existing treatment with people diagnosed with depression (major depression disorder). The secondary objective is to examine the response and remission rates following the switch from a generic SSRI to levomilnacipran ER and augmentation with quetiapine along with examining changes in neurocognitive and apathy measures after the switch.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Changes of Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

  A ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Total scores will range from 0 to 60. Higher scores indicate greater severity of depressive episodes.

  Baseline to Week 8

Secondary Outcomes (10)

• Response Rate

  Week 8

• Remission Rate

  Week 8

• Changes in Neurocognition by Changes in Scores on Reyes Verbal Learning Test

  Baseline to Week 8

• Changes in Neurocognition by Changes in Scores on Scores on Digit Symbol Substitution Test (DSST)

  Baseline to Week 8

• Number of Subjects With Global Improvement in Scores on Clinical Global Impression Scale- Severity (CGI-S)

  Baseline to Week 8

Study Arms (2)

Levomilnacipran

ACTIVE COMPARATOR

Levomilnacipran ER is switched from SSRI.

Drug: Levomilnacipran

Quetiapine

ACTIVE COMPARATOR

Quetiapine XR is added in addition to current SSRI.

Drug: Quetiapine

Interventions

Levomilnacipran DRUG

treating major depression. A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8

Also known as: Fetzima

Levomilnacipran

Quetiapine DRUG

Quetiapine will be started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current antidepressant.

Also known as: Seroquel

Quetiapine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years inclusive
• Current diagnosis of MDD based on DSM-IV criteria
• Able to understand study rules and procedures and willing to sign written informed consent for study participation
• Inadequate response to antidepressants: having a score of ≥14 on the 17-item Hamilton Anxiety Scale (HAMD) and not having a ≥ 50% reduction in HAMD or CGI-S scores from baseline after a retrospective confirmation of an adequate trial of a single antidepressant (defined as a minimum 6-week trial of acceptable therapeutic dose (daily dose ≥ 40 mg of fluoxetine, 40 mg of paroxetine, 20 mg of citalopram, 10 mg of escitalopram, 37.5 mg of paroxetine CR, 150 mg of sertraline, 100 mg of fluvoxamine).
• If female, nonpregnant/nonlactating status
• Duration of current MDD ≥ 4 weeks and \< 24 months
• Not more than 2 treatment failures of adequate antidepressant trials for current episode of MDD

You may not qualify if:

• Has previously participated in a levomilnacipran ER or quetiapine XR or quetiapine clinical study in previous 12 months
• Has 1 or more the following:
• Current or past history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder defined in the DSM- 5
• Diagnosis of alcohol or other substance use disorder (except nicotine and caffeine) as defined in the DSM-5 that has not been in sustained full remission for at least 6 months prior to screening (participant must also have negative urine drug screen prior to baseline).
• Presence or history of a clinically significant neurological disorder (including epilepsy)
• Poorly controlled Hypertension or Diabetes
• uncontrolled narrow-angle glaucoma
• hypersensitivity to levomilnacipran, milnacipran , quetiapine or quetiapine XR
• Neurodegenerative disorder.
• Has a thyroid stimulating hormone value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator.
• Has clinically significant abnormal vital signs as determined by the investigator.
• Has a clinical significant abnormal electrocardiogram.
• Has screening laboratory values greater than 2.5 times the upper or lower limits of normal range or judged to be clinically significant
• Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy or prevent the individual from completing the study.
• Female subjects of childbearing potential not on adequate contraception methods in the opinion of the investigator

Sponsors & Collaborators

• Duke University: lead
• Forest Laboratories: collaborator
• Institute for Advanced Medical Research, Alpharetta, GA: collaborator

Study Sites (1)

Institute for Advanced Medical Research

Alpharetta, Georgia, 30005, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Levomilnacipran; Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Milnacipran; Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Narei Hong
• Organization: Duke University Medical Center

narei.hong@duke.edu

984-215-8493

Study Officials

• Ashwin A Patkar, MD

  Duke Universtiy Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 25, 2016
• Study Start: January 23, 2017
• Primary Completion: June 12, 2018
• Study Completion: June 12, 2018
• Last Updated: August 14, 2019
• Results First Posted: July 2, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)