Clinical TrialTreatment-Resistant Depression (TRD)EsketamineCompleted

A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression (SUSTAIN-2)

Open-label, multicentre, single-group Phase III study (n=802) assessing long-term safety and efficacy of intranasal esketamine plus an oral antidepressant in adults with treatment-resistant depression.

Target Enrollment
802 participants
Study Type
Phase III interventional
Design
Non-randomized

Detailed Description

This open-label, multicentre study evaluated long-term safety and efficacy of intranasal esketamine administered with an oral antidepressant in adults with treatment-resistant depression (TRD).

Study design comprised screening (4 weeks), open-label induction (4 weeks), optimisation/maintenance (48 weeks) and follow-up (4 weeks); participants entered directly or were transferred from a prior double-blind induction study.

Esketamine was self-administered intranasally in a flexible regimen (induction twice-weekly: typically 56 or 84 mg for <65 yrs; ≥65 yrs start 28 mg), then reduced to weekly and individualised; safety and depressive symptoms were monitored throughout.

Study Protocol

Preparation

sessions

Dosing

8 sessions

Integration

sessions

Study Arms & Interventions

Esketamine + antidepressant

experimental

Open-label single-group: intranasal esketamine administered with a newly initiated or continued oral antidepressant; induction twice-weekly for 4 weeks then optimized/maintained weekly or every other week.

Interventions

  • Esketamine56 - 84 mg
    via Intranasal• twice weekly (induction); then weekly or every other week (maintenance)

    Flexible dosing: <65 yrs 56 or 84 mg; ≥65 yrs start 28 mg (28, 56 or 84 mg possible).

  • Compound
    via Oral• daily

    Oral antidepressant co-administered: duloxetine (min 60 mg/day) or escitalopram (min 10 mg/day) or sertraline (50–150 mg/day) or venlafaxine XR (75–225 mg/day); direct-entry start Day 1; transferred-entry continue prior antidepressant.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • A) For Direct-Entry Participants
  • At the time of signing the informed consent form (ICF), participant must be a man or woman ≥18 (or older if the minimum legal age of consent in the country in which the study is taking place is greater than 18)
  • At the start of the screening phase, participant must meet DSM-5 criteria for single-episode MDD (if single-episode MDD, duration ≥2 years) or recurrent MDD, without psychotic features, confirmed by MINI
  • At screening, participant must have a MADRS total score of ≥22
  • At the start of the screening phase, participants must have had nonresponse to ≥2 oral antidepressant treatments in the current episode of depression, as assessed using the MGH-ATRQ and confirmed by documented records
  • B) For Transferred-entry Participants
  • All participants who completed the double-blind induction phase of ESKETINTRD3005, regardless of response status, are eligible if they meet study-specific criteria

Exclusion Criteria

  • Exclusion Criteria:
  • A) For Direct-Entry Participants
  • Prior nonresponse in the current episode to esketamine or ketamine or to all of the 4 oral antidepressant options available for the open-label induction phase (duloxetine, escitalopram, sertraline, venlafaxine XR) per MGH-ATRQ
  • Current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders, current OCD, intellectual disability, autism spectrum disorder, borderline personality disorder, antisocial, histrionic, or narcissistic personality disorder
  • Homicidal ideation/intent per investigator judgement, or suicidal ideation with some intent to act within 6 months prior to screening (per investigator or C-SSRS)
  • History of moderate or severe substance or alcohol use disorder per DSM-5
  • MMSE <25, neurodegenerative disorder, or evidence of mild cognitive impairment
  • B) For Transferred-entry Participants
  • Participant has taken any prohibited therapies that would not permit dosing on Day 1

Study Details

Locations

Unknown facility — New Haven, Connecticut, United States
Unknown facility — Miami, Florida, United States
Unknown facility — Marietta, Georgia, United States
Unknown facility — Iowa City, Iowa, United States
Unknown facility — Wichita, Kansas, United States
Unknown facility — Baltimore, Maryland, United States
Unknown facility — Watertown, Massachusetts, United States
Unknown facility — Cedarhurst, New York, United States
Unknown facility — New York, New York, United States
Unknown facility — Staten Island, New York, United States
Unknown facility — Cincinnati, Ohio, United States
Unknown facility — Allentown, Pennsylvania, United States
Unknown facility — Charleston, South Carolina, United States
Unknown facility — Dallas, Texas, United States
Unknown facility — Wichita Falls, Texas, United States
Unknown facility — Richland, Washington, United States
Unknown facility — Banfield, Argentina
Unknown facility — Buenos Aires, Argentina
Unknown facility — Córdoba, Argentina
Unknown facility — La Plata, Argentina
Unknown facility — Mendoza, Argentina
Unknown facility — Rosario, Argentina
Unknown facility — Adelaide, Australia
Unknown facility — Caulfield, Australia
Unknown facility — Frankston, Australia
Unknown facility — Melbourne, Australia
Unknown facility — Innsbruck, Austria
Unknown facility — Vienna, Austria
Unknown facility — Bruges, Belgium
Unknown facility — Hasselt, Belgium
Unknown facility — Belo Horizonte, Brazil
Unknown facility — Fortaleza, Brazil
Unknown facility — Recife, Brazil
Unknown facility — Rio de Janeiro, Brazil
Unknown facility — Santo André, Brazil
Unknown facility — São José do Rio Preto, Brazil
Unknown facility — São Paulo, Brazil
Unknown facility — Burgas, Bulgaria
Unknown facility — Kardzhali, Bulgaria
Unknown facility — Kazanlak, Bulgaria
Unknown facility — Pazardzhik, Bulgaria
Unknown facility — Pleven, Bulgaria
Unknown facility — Plovdiv, Bulgaria
Unknown facility — Rousse, Bulgaria
Unknown facility — Sofia, Bulgaria
Unknown facility — Varna, Bulgaria
Unknown facility — Helsinki, Finland
Unknown facility — Kuopio, Finland
Unknown facility — Paris, France
Unknown facility — Poitiers, France
Unknown facility — Toulon, France
Unknown facility — Tours, France
Unknown facility — Berlin, Germany
Unknown facility — Bochum, Germany
Unknown facility — Oranienburg-Sachsenhausen, Germany
Unknown facility — Kaunas, Lithuania
Unknown facility — Šilutė, Lithuania
Unknown facility — Vilnius, Lithuania
Unknown facility — Ipoh, Malaysia
Unknown facility — Johor Bahru, Malaysia
Unknown facility — Kuala Lumpur, Malaysia
Unknown facility — Acapulco, Mexico
Unknown facility — Durango, Mexico
Unknown facility — Mexico City, Mexico
Unknown facility — México, Mexico
Unknown facility — Monterrey, Mexico
Unknown facility — Gdansk, Poland
Unknown facility — Cape Town, South Africa
Unknown facility — Garsfontein, South Africa
Unknown facility — Pretoria, South Africa
Unknown facility — Gwangju, South Korea
Unknown facility — Gyeonggi-do, South Korea
Unknown facility — Seoul, South Korea
Unknown facility — Badajoz, Spain
Unknown facility — Bilbao, Spain
Unknown facility — Madrid, Spain
Unknown facility — Ourense, Spain
Unknown facility — Oviedo, Spain
Unknown facility — Sant Boi de Llobregat, Spain
Unknown facility — Torrevieja, Spain
Unknown facility — Valencia, Spain
Unknown facility — Zamora, Spain
Unknown facility — Gothenburg, Sweden
Unknown facility — Halmstad, Sweden
Unknown facility — Lund, Sweden
Unknown facility — Skövde, Sweden
Unknown facility — Solna, Sweden
Unknown facility — Stockholm, Sweden
Unknown facility — Umeå, Sweden
Unknown facility — Kaohsiung City, Taiwan
Unknown facility — New Taipei City, Taiwan
Unknown facility — Taichung, Taiwan
Unknown facility — Tainan, Taiwan
Unknown facility — Taipei, Taiwan
Unknown facility — Taoyuan, Taiwan
Unknown facility — Ankara, Turkey (Türkiye)
Unknown facility — Bursa, Turkey (Türkiye)
Unknown facility — Gaziantep, Turkey (Türkiye)
Unknown facility — Istanbul, Turkey (Türkiye)
Unknown facility — Kocaeli, Turkey (Türkiye)
Unknown facility — Manisa, Turkey (Türkiye)
Unknown facility — Bristol, United Kingdom
Unknown facility — Chesterfield, United Kingdom
Unknown facility — Derby, United Kingdom
Unknown facility — London, United Kingdom
Unknown facility — Middlesbrough, United Kingdom
Unknown facility — Northampton, United Kingdom
Unknown facility — Oxford, United Kingdom
Unknown facility — Preston, United Kingdom

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