Clinical TrialMajor Depressive Disorder (MDD)EsketaminePlaceboCompleted

A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for Suicide (ASPIRE II)

This double-blind, randomized, placebo-controlled trial (n=226) aimed to assess the efficacy and safety of intranasal esketamine 84 milligrams (mg) in addition to comprehensive standard care for rapidly reducing Major Depressive Disorder (MDD) symptoms, including suicidal ideation, in adults at imminent risk for suicide.

Target Enrollment
230 participants
Study Type
Phase III interventional
Design
Randomized, double Blind

Detailed Description

Randomized, double-blind, parallel-group Phase 3 study comparing intranasal esketamine 84 mg plus comprehensive standard of care versus intranasal placebo plus standard of care in adults hospitalised for imminent suicide risk; primary efficacy measured by change in MADRS total score at 24 hours post first dose.

Dosing: esketamine or placebo administered intranasally on Days 1, 4, 8, 11, 15, 18, 22 and 25 (8 administrations total); standard of care antidepressant therapy initiated on Day 1; participants typically hospitalised for at least 14 days per protocol.

Study Protocol

Preparation

sessions

Dosing

8 sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Esketamine + Standard of care

experimental

Intranasal esketamine 84 mg twice weekly for 4 weeks plus standard of care antidepressant therapy.

Interventions

  • Esketamine84 mg
    via Other• two times per week• 8 doses total

    Intranasal administration on Days 1, 4, 8, 11, 15, 18, 22, and 25.

  • Compound
    via Other

    Standard of care antidepressant therapy determined by treating physician; initiated on Day 1.

Placebo + Standard of care

inactive

Intranasal placebo twice weekly for 4 weeks plus standard of care antidepressant therapy.

Interventions

  • Placebo
    via Other• two times per week• 8 doses total

    Intranasal placebo on Days 1, 4, 8, 11, 15, 18, 22, and 25.

  • Compound
    via Other

    Standard of care antidepressant therapy determined by treating physician; initiated on Day 1.

Participants

Ages
18 – 64
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Participant must meet Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the Mini International Psychiatric Interview (MINI)
  • Participants must have current suicidal ideation with intent, confirmed by a "Yes" response to Question B3 [Think (even momentarily) about harming or of hurting or of injuring yourself: with at least some intent or awareness that you might die as a result; or think about suicide (ie, about killing yourself)?] AND Question B10 [Intend to act on thoughts of killing yourself?] obtained from the MINI
  • In the physician's opinion, acute psychiatric hospitalization is clinically warranted due to participant's imminent risk of suicide
  • Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than (>) 28 predose on Day 1
  • As part of standard of care treatment, participant agrees to be hospitalized voluntarily for a recommended period of 14 days after randomization (may be shorter or longer if clinically warranted in the investigator's opinion) and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25)

Exclusion Criteria

  • Exclusion Criteria:
  • Participant has a current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, or obsessive compulsive disorder
  • Participant currently meets DSM-5 criteria for borderline personality disorder. Note: Participant not meeting full DSM-5 criteria for borderline personality disorder but exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should also be excluded
  • Participant has a current clinical diagnosis of autism, dementia, or intellectual disability
  • Participant has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features
  • Participant meets the DSM-5 severity criteria for moderate or severe substance or alcohol use disorder, (except for nicotine or caffeine), within the 12 months before Screening. A history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3,4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related use disorder is exclusionary
  • Participant has a history or current signs and symptoms of liver or renal insufficiency, clinically significant cardiac (including unstable coronary artery disease and congestive heart failure, tachyarrhythmias and recent myocardial infarction) or vascular, pulmonary, gastrointestinal, endocrine (including uncontrolled hyperthyroidism), neurologic (including current or past history of seizures except uncomplicated childhood febrile seizures with no sequelae), hematologic, rheumatologic, or metabolic (including severe dehydration/ hypovolemia) disease
  • Participant has known allergies, hypersensitivity, intolerance or contraindications to esketamine or ketamine or its excipients

Study Details

Locations

University of California San Diego/Psychiatry — San Diego, California, United States
Sharp Mesa Vista Hospital — San Diego, California, United States
University of Conneticut School of Medicine — Farmington, Connecticut, United States
University of Miami Health System — Miami, Florida, United States
Innovative Clinical Research Inc — North Miami, Florida, United States
University of South Florida — Tampa, Florida, United States
Atlanta Behavioral Research, LLC — Atlanta, Georgia, United States
Memorial Medical Center — Springfield, Illinois, United States
Neuroscience Research Institute — Winfield, Illinois, United States
Lake Charles Clinical Trials — Lake Charles, Louisiana, United States
John Hopkins Hospital — Baltimore, Maryland, United States
Altea Research Institute — Las Vegas, Nevada, United States
The Zucker Hillside Hospital — Glen Oaks, New York, United States
Stony Brook University Medical Center — Stony Brook, New York, United States
University of North Carolina — Chapel Hill, North Carolina, United States
University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience — Cincinnati, Ohio, United States
East Tennessee State University — Johnson City, Tennessee, United States
University of Wisconsin Medical Center — Madison, Wisconsin, United States
Clínica Privada Banfield S.A — Banfield, Argentina
Hospital Fleni — Ciudad de Buenos Aires, Argentina
Sanatorio Prof. Leon S. Morra — Córdoba, Argentina
Clinica Privada de Salud Mental Santa Teresa de Ávila — La Plata, Argentina
Medical University Vienna MUV — Vienna, Austria
Klinikum Wels Grieskirchen — Wels, Austria
AZ Sint Jan Brugge Oostende AV — Bruges, Belgium
UZ Gent — Ghent, Belgium
ARIADNE — Lede, Belgium
Universidade Federal De Minas Gerais - Hospital das Clínicas — Belo Horizonte, Brazil
Universidade Federal Do Ceara — Fortaleza, Brazil
Instituto Bairral de Psiquiatria — Itapira, Brazil
Hospital Universitario Professor Edgar Santos — Salvador, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clínicos — Santo André, Brazil
Hospital Das Clinicas Da Faculdade De Medicina Da USP — São Paulo, Brazil
St. Michael's Hospital — Toronto, Ontario, Canada
Institut universitaire en sante mentale de Montreal — Montreal, Quebec, Canada
Fakultni nemocnice Brno — Brno, Czechia
Nemocnice s pol. Havirov, p.o. — Havířov, Czechia
Narodni ustav dusevniho zdravi — Klecany, Czechia
Vseobecna Fakultní Nemocnice — Prague, Czechia
Ústrední vojenské nemocnice Praha — Prague, Czechia
Hôpital de Bohars — Bohars, France
CHRU Montpellier Hopital Lapeyronie — Montpellier, France
CHU Caremeau — Nîmes, France
Hopital Sainte Anne — Paris, France
CHU Saint Etienne Hopital Nord — Saint-Priest-en-Jarez, France
CHU Toulouse — Toulouse, France
Hospital of Lithuanian University of Health Sciences Kaunas Clinics — Kaunas, Lithuania
Republic Kaunas Hospital — Kaunas County, Lithuania
Vilnius Mental Health Center — Vilnius, Lithuania
Uniwersyteckie Centrum Kliniczne — Gdansk, Poland
Szpital Specjalistyczny im H Klimontowicza Oddzial Psychiatryczny — Gorlice, Poland
SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych — Lodz, Poland
Klinika Psychiatryczna WUM Mazowieckie Specjalistyczne Centrum Zdrowia im prof Jana Mazurkiewicza — Pruszków, Poland
Hosp Univ Vall D Hebron — Barcelona, Spain
Inst. Internac. Neurociencias Aplicadas — Barcelona, Spain
Hosp. Univ. de Basurto — Bilbao, Spain
Clinica Univ. de Navarra — Pamplona, Spain
Bursa Sevket Yilmaz Research and Training Hospital — Bursa, Turkey (Türkiye)
Uludag University Medical Faculty — Bursa, Turkey (Türkiye)
Sisli Etfal Research Training Hospital — Istanbul, Turkey (Türkiye)
Samsun Psychiatric Hospital — Samsun, Turkey (Türkiye)

Your Library