Clinical TrialTreatment-Resistant Depression (TRD)EsketamineEsketamineEsketaminePlaceboCompleted

A multicentre, double-blind, randomised, placebo - controlled phase II study to assess efficacy, safety and pharmacokinetics of inhaled Esketamine in subject with treatment-resistant depression in the course of Major Depressive Disorder

Multicentre, double-blind, randomised, placebo-controlled Phase II trial (n=88) evaluating inhaled esketamine (three dose levels) versus placebo for treatment-resistant depression; primary endpoint MADRS change at Day 14; includes PK assessments on Day 1 and Day 11.

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Target Enrollment
88 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

This multicentre double-blind randomised Phase II study (EudraCT 2018-001963-22) compared three dose levels of inhaled esketamine delivered by dry powder inhaler versus matching placebo in adults (18–65) with treatment-resistant major depressive disorder (n=88).

Primary outcome was change from baseline in MADRS total score at Day 14. Secondary and safety assessments included CGI-S, C-SSRS, CADSS, BPRS, vitals, laboratory measures, withdrawal symptoms (PWC-20), cognition (MoCA) and PK of esketamine and esnorketamine (Day 1 and Day 11).

Subjects were hospitalised around dosing visits per protocol and excluded for significant medical comorbidity, recent substance dependence, or elevated suicidal risk.

Study Arms & Interventions

Esketamine low dose

experimental

Inhaled esketamine, low dose level (per protocol).

Interventions

  • Esketamine
    via Inhalation• multiple doses

    Low dose level per protocol; dosing schedule as defined in protocol (multiple administrations including Day 1 and Day 11).

Esketamine mid dose

experimental

Inhaled esketamine, mid dose level (per protocol).

Interventions

  • Esketamine
    via Inhalation• multiple doses

    Mid dose level per protocol; dosing schedule as defined in protocol (multiple administrations including Day 1 and Day 11).

Esketamine high dose

experimental

Inhaled esketamine, high dose level (per protocol).

Interventions

  • Esketamine
    via Inhalation• multiple doses

    High dose level per protocol; dosing schedule as defined in protocol (multiple administrations including Day 1 and Day 11).

Placebo

inactive

Inhalation placebo (powder)

Interventions

  • Placebo
    via Inhalation• multiple doses

    Matching inhalation powder placebo.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • 1. Gender: female or male.
  • 2. Age 18–65 years inclusive at Screening.
  • 3. DSM-5 diagnosis of major depressive disorder (MDD) without psychotic features, confirmed by MINI.
  • 4. MADRS total score ≥25 at Screening and predose on Day 1.
  • 5. Treatment resistant: inadequate response to ≥2 antidepressants at adequate dose/duration in current episode.
  • 6. On stable monotherapy antidepressant (per protocol) and remain on non-investigational antidepressant therapy from Screening through Day 14.
  • 7. Agree to voluntary hospitalisation from 12 h before first IMP administration until Day 6; further hospitalisation from Day 6–14 per investigator discretion; mandatory hospitalisation 12 h before each IMP to 24 h after each administration and from evening of Day 13 to end of Day 14 examinations.
  • 8. Medically stable per labs, exam, vitals and 12-lead ECG (QTcB assessed).
  • 9. Agree to blood sample for DNA analysis.
  • 10. Able to give informed consent and comply with protocol requirements.
  • 11. Women/men of childbearing potential agree to stipulated contraception requirements.

Exclusion Criteria

  • 1. Current DSM-5 diagnosis other than MDD (eg psychotic disorders, personality disorders, intellectual disability, PTSD, OCD, bipolar disorder).
  • 2. Suicidal ideation: MADRS suicidality subscale ≥2 and/or C-SSRS score ≥4 at Screening, or history of suicidal thoughts within 6 months or suicide attempt within 1 year prior to Screening.
  • 3. History or current signs of COPD, asthma, significant hepatic/renal insufficiency or major uncontrolled medical conditions that may affect safety.
  • 4. Uncontrolled hypertension despite treatment at Screening or on Day 0/Day 1 prior to IMP.
  • 5. Upper respiratory tract/chest infection or inflammation within 2 weeks prior to first IMP or during treatment phase.
  • 6. Participation in another clinical trial with IMP within 90 days prior to Screening.
  • 7. Known allergy/hypersensitivity to esketamine/ketamine or excipients.
  • 8. Blood donation ≥300 mL within 30 days prior to inclusion.
  • 9. Substance abuse/dependence (except nicotine/caffeine) within 2 years prior to Screening.
  • 10. Lifetime abuse/dependence on ketamine or phencyclidine.
  • 11. Positive HBsAg, anti-HCV or anti-HIV.
  • 12. Positive pregnancy test or lactation.
  • 13. Positive drug screen (except benzodiazepines during follow-up) or positive breath alcohol test.
  • 14. Inability or unwillingness to provide written informed consent.
  • 15. Any other reason investigator deems subject unsuitable.

Study Protocol, Arms & Participants

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Study Details

Locations

Poland

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