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.
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
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
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
BMI
-
Psychosis History
-
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