Major Depressive DisorderPhase 3NCT02720198
Levomilnacipran ER vs. Adjunctive Quetiapine for Adults With Inadequate Relief With SSRIs in MDD
A Phase 3 study testing Levomilnacipran and Quetiapine in people with Major Depressive Disorder, run by Duke University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Levomilnacipran and Quetiapine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jan 2017to 12 Jun 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
- o If the female is childbearing, she must agree to use appropriate contraceptive measures for the duration of the study and for one month afterwards. Medically acceptable contraceptives include: (1) surgical sterilization (such as tubal ligation of hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants, or injections), (3) barrier methods (such as condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures such as Plan B ™, sold for emergency use after unprotected sex, are not acceptable methods for routine use. If the female does become pregnant during this study she must inform the study physician immediately.
- Has a significant risk of suicide according to Columbia Suicide Severity Rating Scale (CSSRS) or in the clinical judgment of the investigator
- History of suicide attempt in the previous 12 months
- MDD with postpartum onset, psychotic features or seasonal features
- Hamilton Anxiety Scale (HAM-A) baseline score ≥ 24
- Failure of ≥ 3 adequate trials of different antidepressants for the current episode of MDD
- ≥ 3 episodes major depression in previous 12 months or ≥ 8 lifetime episodes of MDD
- Current or previous use of an atypical or typical antipsychotic agent for augmentation of major depression or treatment of psychotic depression, mania psychosis, or agitation. Previous use of antipsychotics for insomnia will be permitted.
Trial locations and contacts
1 site in 1 country.
United States1 site
Institute for Advanced Medical Research
Alpharetta, Georgia, 30005
About this study
Official title: A Randomized Trial Comparing Efficacy and Tolerability of Levomilnacipran Switch Versus Adjunctive Quetiapine in Major Depressive Disorder (MDD) With Inadequate Response to SSRIs
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.
Read the detailed description
- Study Design 1) An 8-week, randomized rater blinded parallel group, 2-arm trial 2) Trial duration - 9 weeks 3) Drug doses
- Levomilnacipran ER; Switching to a flexible dose regime of levomilnacipran ER 40-120 mg/day after initial dose of 20mg.
- Quetiapine XR; Adjunct a flexible dose regimen of quetiapine XR 150-300 mg/day after initial dose of 50mg.
- Objective 1) To compare the efficacy and tolerability of switching to levomilnacipran ER (40-120 mg/d) versus augmentation with quetiapine XR 150-300 mg/day to the patients' existing treatment for patients with inadequate relief on generic SSRIs in patients with MDD.
- To examine the response following the switch from generic SSRI to levomilnacipran ER and augmentation with quetiapine XR.
- To examine changes in neurocognitive and apathy measures after switching from SSRI to levomilnacipran ER and after augmentation with quetiapine XR in MDD
- Conditions
- Major Depressive Disorder
- Being tested
- Levomilnacipran, Quetiapine
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevomilnacipranDrug
Also called Fetzima
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
QuetiapineDrug
Also called Seroquel
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.
| Study group | Role | What they receive |
|---|---|---|
| Levomilnacipran | Active comparator | Levomilnacipran ER is switched from SSRI. Receives: Drug: Levomilnacipran |
| Quetiapine | Active comparator | Quetiapine XR is added in addition to current SSRI. Receives: Drug: Quetiapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 8
Secondary outcomes (10)
Response Rate
Remission was defined as [>or=50% reduction in MADRS score with MADRS <or=10] and response was defined as [>or=50% reduction in MADRS with MADRS >10]. Response rate included remission and response.
Measured: Week 8
Remission Rate
Remission was defined as [>or=50% reduction in MADRS score with MADRS <or=10]
Measured: Week 8
Changes in Neurocognition by Changes in Scores on Reyes Verbal Learning Test
Number of words correctly recalled by the respondent is recorded. 1 point for each word correctly recalled. Total score range of 0-40. Higher scores mean better cognitive function.
Measured: Baseline to Week 8
Changes in Neurocognition by Changes in Scores on Scores on Digit Symbol Substitution Test (DSST)
DSST measures working memory and visuospatial processing. 1 point for each object correctly substituted from number to each matched symbol. Total score range of 0-89. Higher scores mean better cognitive function.
Measured: Baseline to Week 8
Number of Subjects With Global Improvement in Scores on Clinical Global Impression Scale- Severity (CGI-S)
CGI-S is a 7 point scale that assess the severity of illness and requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. It is used to assess the clinician's view of the patient's global functioning. Total score range of 0-7.
Measured: Baseline to Week 8
Number of Subjects With General Improvement in Scores on Clinical Global Impression Scale- Improvement (CGI-I)
CGI-I a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. It is used to assess the clinician's view of the patient's global functioning. Total score range of 0-7.
Measured: Baseline to Week 8
Changes of Anxiety Symptoms in Scores on Hamilton Anxiety Rating Scale (HAM-A)
A questionnaire used by clinicians to rate the severity of a patient's anxiety. Total score range of 0-48. A higher score indicates greater anxiety.
Measured: Baseline to Week 8
Changes of Quality of Life in Scores on Sheehan Disability Scale (SDS) Total
A self-reported brief scale to assess impairment of work/school, social life and family and home. Total score range of 0-30. A higher score indicates greater impairment.
Measured: Baseline to Week 8
Changes in Scores on Apathy Evaluation Scale (AES).
Self-Administered assessment measuring lack of motivation not attributable to diminished level of consciousness, cognitive impairment, or emotional distress. Total scores range from 0-54. Higher scores indicate greater apathy.
Measured: Baseline to Week 8
Changes in Sexual Dysfunction by Changes in Scores on Arizona Sexual Experience Scale (ASEX)
ASEX is scale for sexual dysfunction to assess safety and tolerability of medication. Total scores range from 5-30. Higher scores indicate greater sexual dysfunction.
Measured: Baseline to Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2016 (estimated)
- Study start23 Jan 2017
- Primary completion12 Jun 2018
- Study completion12 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories, Institute for Advanced Medical Research, Alpharetta, GA
- Responsible party
- Sponsor
- Investigators
- Ashwin A Patkar, MD, Principal investigator, Duke Universtiy Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02720198
- Sponsor's protocol ID
- Pro00064983
- Status last verified
- Aug 2019
- First submitted
- 16 Mar 2016
- Last updated
- 14 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial Comparing Efficacy and Tolerability of Levomilnacipran Switch Versus Adjunctive Quetiapine in Major Depressive Disorder (MDD) With Inadequate Response to SSRIs
- ClinicalTrials.gov ID
- NCT02720198
- Acronym / sponsor ID
- Pro00064983
- Conditions
- Major Depressive Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Forest Laboratories, Institute for Advanced Medical Research, Alpharetta, GA
- Study start
- 23 Jan 2017 (actual)
- Primary completion
- 12 Jun 2018 (actual)
- Study completion
- 12 Jun 2018 (actual)
- First posted
- 25 Mar 2016 (estimated)
- Results
- Posted 2 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- Study Design 1) An 8-week, randomized rater blinded parallel group, 2-arm trial 2) Trial duration - 9 weeks 3) Drug doses
- Levomilnacipran ER; Switching to a flexible dose regime of levomilnacipran ER 40-120 mg/day after initial dose of 20mg.
- Quetiapine XR; Adjunct a flexible dose regimen of quetiapine XR 150-300 mg/day after initial dose of 50mg.
- Objective 1) To compare the efficacy and tolerability of switching to levomilnacipran ER (40-120 mg/d) versus augmentation with quetiapine XR 150-300 mg/day to the patients' existing treatment for patients with inadequate relief on generic SSRIs in patients with MDD.
- To examine the response following the switch from generic SSRI to levomilnacipran ER and augmentation with quetiapine XR.
- To examine changes in neurocognitive and apathy measures after switching from SSRI to levomilnacipran ER and after augmentation with quetiapine XR in MDD
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levomilnacipran | Active comparator | Drug: LevomilnacipranLevomilnacipran ER is switched from SSRI. |
| Quetiapine | Active comparator | Drug: QuetiapineQuetiapine XR is added in addition to current SSRI. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (23 listed)
- Has previously participated in a levomilnacipran ER or quetiapine XR or quetiapine clinical study in previous 12 months
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevomilnacipranAlso: Fetzimatreating 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 | Drug | Levomilnacipran |
| QuetiapineAlso: SeroquelQuetiapine 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. | Drug | Quetiapine |
Primary outcome
Changes of Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Time frame: Baseline to Week 8
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.
10 secondary outcomes
Response Rate
Time frame: Week 8
Remission Rate
Time frame: Week 8
Changes in Neurocognition by Changes in Scores on Reyes Verbal Learning Test
Time frame: Baseline to Week 8
Changes in Neurocognition by Changes in Scores on Scores on Digit Symbol Substitution Test (DSST)
Time frame: Baseline to Week 8
Number of Subjects With Global Improvement in Scores on Clinical Global Impression Scale- Severity (CGI-S)
Time frame: Baseline to Week 8
Number of Subjects With General Improvement in Scores on Clinical Global Impression Scale- Improvement (CGI-I)
Time frame: Baseline to Week 8
Changes of Anxiety Symptoms in Scores on Hamilton Anxiety Rating Scale (HAM-A)
Time frame: Baseline to Week 8
Changes of Quality of Life in Scores on Sheehan Disability Scale (SDS) Total
Time frame: Baseline to Week 8
Changes in Scores on Apathy Evaluation Scale (AES).
Time frame: Baseline to Week 8
Changes in Sexual Dysfunction by Changes in Scores on Arizona Sexual Experience Scale (ASEX)
Time frame: Baseline to Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashwin A Patkar, MD principal investigator
Duke Universtiy Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Levomilnacipran and Quetiapine in people with Major Depressive Disorder, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes of Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score (time frame: Baseline to Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2019.