NCT03249311

Brief Summary

Levomilnacipran is an antidepressant currently approved in Canada to treat Major Depressive Disorder (MDD). Thirty-six healthy male participants will receive escalating doses of levomilnacipran, duloxetine, or placebo every 7 days (+/- 1 day) throughout a 20 - 28 day period. After each dose escalation study participants will be asked to come to the clinic to conduct the necessary tests - these will include tyramine pressor tests as well as blood draws. The results of this study will allow the investigators to determine the dose(s) of levomilnacipran at which reuptake inhibition of norepinephrine and serotonin (chemicals utilized by nerve cells to transmit information to other cells) is achieved.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
36

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Mar 2018

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 20, 2017

Completed
26 days until next milestone

First Posted

Study publicly available on registry

August 15, 2017

Completed
7 months until next milestone

Study Start

First participant enrolled

March 2, 2018

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2019

Completed
2.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2022

Completed
Last Updated

October 6, 2021

Status Verified

October 1, 2021

Enrollment Period

1.8 years

First QC Date

July 20, 2017

Last Update Submit

October 5, 2021

Conditions

None (i.e. Healthy Volunteers)

Keywords

LevomilnacipranAntidepressantOttawaSelective Norepinephrine Reuptake InhibitorHealthy malesTyramine responseSerotoninNorepinephrine

Outcome Measures

Primary Outcomes (1)

  • Primary End Point

    The degree of norepinephrine reuptake in response to the increasing levels of the study medication will be assessed and compared between three treatment groups.

    24 months

Secondary Outcomes (1)

  • Secondary End Points

    24 months

Study Arms (3)

Levomilnacipran

EXPERIMENTAL

Participants will be randomly assigned to receive levomilnacipran, duloxetine, or placebo

Drug: Levomilnacipran

Duloxetine (Cymbalta)

ACTIVE COMPARATOR

Participants will be randomly assigned to receive levomilnacipran, duloxetine, or placebo

Drug: Duloxetine

Levomilnacipran Placebo-matched capsules

PLACEBO COMPARATOR

Participants will be randomly assigned to receive levomilnacipran, duloxetine, or placebo

Drug: Placebos

Interventions

LevomilnacipranDRUG

Escalating doses of 40 to 120mg/day every 7 days (+/- 1 day) throughout a 20-26 day period.

Also known as: Fetzima
Levomilnacipran
DuloxetineDRUG

Escalating doses of 40 to 120mg/day every 7 days (+/- 1 day) throughout a 20-26 day period.

Also known as: Cymbalta
Duloxetine (Cymbalta)
PlacebosDRUG

Escalating doses of 40 to 120mg/day every 7 days (+/- 1 day) throughout a 20-26 day period.

Levomilnacipran Placebo-matched capsules

Eligibility Criteria

Age18 Years - 40 Years
Sexmale(Gender-based eligibility)
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Male participants between 18 and 40 years-old
  • Written informed consent signed by the participant

You may not qualify if:

  • Lifetime personal history of diagnosis of major depressive disorder according to the DSM-V (American Psychiatric Association, 2013) using the Structured Clinical Interview for DSM-V Axis I Disorders, Research Version, Non-patient Edition (SCID-5-RV for DSM-V; First et al., 2015)
  • A history of suicidal ideation and behaviour, including self-harm and/or harm to others.
  • A history of substance abuse and/or dependence.
  • A positive drug screen for illicit drugs
  • Substantial alcohol use
  • Current use of Monoamine Oxidase Inhibitors (MAOIs), including the antibiotic linezolid and the thiazine dye methylthioninium chloride (methylene blue)
  • Current use of serotonin-precursors (such as L-tryptophan, oxitriptan)
  • Current use of serotonergic drugs (triptans, certain tricyclic antidepressants, lithium, tramadol, St. John's Wort)
  • Concomitant use of NSAIDS, ASA, and other anticoagulants.
  • Current use of Thioridazine
  • Current use of CYP1A2 Inhibitors
  • Current use of Triptans (5HT1 Agonists)
  • Blood pressure greater than 140/90 and/or a pulse rate greater than 90 bpm
  • Recent history of myocardial infarction, cerebrovascular accident, cardiac arrhythmias, or unstable heart disease.
  • Evidence of significant physical illness contraindicating the use of levomilnacipran and duloxetine found on the physical exam or in the laboratory data obtained during the first week of the study
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Institute of Mental Health Research, Royal Ottawa Mental Health Centre

Ottawa, Ontario, K1Z 7K4, Canada

Location

Related Publications (10)

  • Asnis GM, Henderson MA. Levomilnacipran for the treatment of major depressive disorder: a review. Neuropsychiatr Dis Treat. 2015 Jan 9;11:125-35. doi: 10.2147/NDT.S54710. eCollection 2015.

    PMID: 25657584BACKGROUND

  • Auclair AL, Martel JC, Assie MB, Bardin L, Heusler P, Cussac D, Marien M, Newman-Tancredi A, O'Connor JA, Depoortere R. Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety. Neuropharmacology. 2013 Jul;70:338-47. doi: 10.1016/j.neuropharm.2013.02.024. Epub 2013 Mar 13.

    PMID: 23499664BACKGROUND

  • Blier P, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Debonnel G. Effects of different doses of venlafaxine on serotonin and norepinephrine reuptake in healthy volunteers. Int J Neuropsychopharmacol. 2007 Feb;10(1):41-50. doi: 10.1017/S1461145705006395. Epub 2006 May 11.

    PMID: 16690005BACKGROUND

  • Aldosary F, Norris S, Tremblay P, James JS, Ritchie JC, Blier P. Differential Potency of Venlafaxine, Paroxetine, and Atomoxetine to Inhibit Serotonin and Norepinephrine Reuptake in Patients With Major Depressive Disorder. Int J Neuropsychopharmacol. 2022 Apr 19;25(4):283-292. doi: 10.1093/ijnp/pyab086.

    PMID: 34958348BACKGROUND

  • Debonnel G, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Blier P. Differential physiological effects of a low dose and high doses of venlafaxine in major depression. Int J Neuropsychopharmacol. 2007 Feb;10(1):51-61. doi: 10.1017/S1461145705006413. Epub 2006 May 11.

    PMID: 16690006BACKGROUND

  • First, M.B., Williams, J.B.W., Karg, R.S., & Spitzer, R.L. (2015). Structured clinical interview for DSM-5-research version. Arlington: American Psychiatric Association.

    BACKGROUND

  • Gobbi G, Slater S, Boucher N, Debonnel G, Blier P. Neurochemical and psychotropic effects of bupropion in healthy male subjects. J Clin Psychopharmacol. 2003 Jun;23(3):233-9. doi: 10.1097/01.jcp.0000084023.22282.03.

    PMID: 12826985BACKGROUND

  • Turcotte JE, Debonnel G, de Montigny C, Hebert C, Blier P. Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects. Neuropsychopharmacology. 2001 May;24(5):511-21. doi: 10.1016/S0893-133X(00)00220-7.

    PMID: 11282251BACKGROUND

  • Vincent S, Bieck PR, Garland EM, Loghin C, Bymaster FP, Black BK, Gonzales C, Potter WZ, Robertson D. Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles. Circulation. 2004 Jun 29;109(25):3202-7. doi: 10.1161/01.CIR.0000130847.18666.39. Epub 2004 Jun 7.

    PMID: 15184278BACKGROUND

  • Nikolitch K, Phillips JL, Daniels S, Blier P. Levomilnacipran, but Not Duloxetine, Inhibits Serotonin and Norepinephrine Reuptake Throughout Its Therapeutic Range. J Clin Psychiatry. 2025 Aug 25;86(3):25m15867. doi: 10.4088/JCP.25m15867.

    PMID: 40875503DERIVED

MeSH Terms

Interventions

LevomilnacipranDuloxetine Hydrochloride

Intervention Hierarchy (Ancestors)

MilnacipranCyclopropanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsThiophenesSulfur CompoundsHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Pierre Blier, MD

    The Royal's Institute of Mental Health Research

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Endowed Research Chair and Director of Mood Disorders Research Unit

Study Record Dates

First Submitted

July 20, 2017

First Posted

August 15, 2017

Study Start

March 2, 2018

Primary Completion

December 31, 2019

Study Completion

May 1, 2022

Last Updated

October 6, 2021

Record last verified: 2021-10

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)