Clinical TrialBipolar DisorderEsketamineEsketamineEsketaminePlaceboCompleted

A multicentre, double-blind, randomised, placebo - controlled phase II study to assess efficacy, safety and pharmacokinetics of inhaled Esketamine in subjects with treatment-resistant bipolar depression

Double-blind, randomised, placebo-controlled Phase II trial (n=88) in Poland testing inhaled esketamine (inhalation powder) versus placebo in adults 18–65 with treatment-resistant bipolar depression to assess efficacy, safety and pharmacokinetics.

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

Detailed Description

Multicentre, double-blind, randomised, placebo-controlled Phase II study comparing multiple-dose inhaled esketamine versus placebo in adults with treatment-resistant bipolar depression; primary outcome is change in MADRS total score at Day 14 versus baseline.

Secondary and exploratory assessments include durability/time-to-relapse, CGI-S, C-SSRS, CADSS, BPRS, safety vitals and labs, withdrawal symptoms, cognitive effects (MoCA), and PK of esketamine and esnorketamine (Day 1 and Day 11).

Study Protocol

Preparation

sessions

Dosing

sessions

Integration

sessions

Therapeutic Protocol

other

Study Arms & Interventions

Esketamine low

experimental

Inhaled esketamine (inhalation powder) active arm, low strength

Interventions

  • Esketamine4 mg
    via Inhalation• multiple doses

    Strength listed in protocol as 4 mg per unit; dosing schedule per protocol (multiple administrations through Day 11).

Esketamine mid

experimental

Inhaled esketamine active arm, mid strength

Interventions

  • Esketamine4 mg
    via Inhalation• multiple doses

    Protocol specifies inhalation powder strength 4 mg; multiple-dose regimen per protocol.

Esketamine high

experimental

Inhaled esketamine active arm, high strength

Interventions

  • Esketamine4 mg
    via Inhalation• multiple doses

    Protocol specifies inhalation powder strength 4 mg; multiple-dose regimen per protocol.

Placebo

inactive

Inhalation powder placebo comparator

Interventions

  • Placebo
    via Inhalation• multiple doses

    Placebo inhalation powder matched to active arms.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • 1. Male or female, aged 18–65 inclusive at screening.
  • 2. DSM-5 diagnosis of depressive episode in Bipolar Disorder type I or II without psychotic features, confirmed by MINI.
  • 3. MADRS total score ≥24 at screening and predose on Day 1.
  • 4. Treatment resistant in current depressive episode: inadequate response to ≥2 adequate mood-stabilising regimens in current episode (adequate dose and ≥6 weeks).
  • 5. On a stable mood-stabilising regimen (per protocol) and willing to continue it through Day 14.
  • 6. Willing to be voluntarily hospitalised from 12 h before first IMP administration until end of Day 14 treatment phase.
  • 7. Medically stable on labs, exam, vitals and 12-lead ECG per investigator judgment.
  • 8. Comfortable with self-administration of inhaled medication and able to follow instructions.
  • 9. Willing to provide blood for DNA analysis and to use contraception per protocol.

Exclusion Criteria

  • 1. Current DSM-5 diagnosis other than bipolar disorder (eg psychotic disorders, personality disorder, MDD, PTSD, OCD).
  • 2. Rapid-cycling bipolar disorder (≥4 episodes/year).
  • 3. YMRS >12 at screening or subsequent assessments.
  • 4. Suicidal ideation per MADRS suicidal item ≥2 and/or C-SSRS ≥4 at screening, history of suicidal thoughts within 6 months or suicide attempt within 1 year.
  • 5. COPD, asthma, significant uncontrolled cardiac, hepatic, renal, pulmonary, endocrine, neurologic, hematologic, rheumatologic or metabolic disturbances per investigator judgment.
  • 6. Uncontrolled hypertension despite treatment at screening or Day 0/1 prior to IMP.
  • 7. Upper respiratory or chest infection/inflammation within 2 weeks before first IMP or during treatment phase.
  • 8. Participation in another clinical trial with IMP within 90 days prior to screening.
  • 9. Known allergy or contraindication to esketamine/ketamine or excipients.
  • 10. Blood donation ≥300 mL within 30 days prior to inclusion.
  • 11. Substance use disorder or dependence (except nicotine/caffeine) within 2 years; lifetime ketamine or PCP dependence.
  • 12. Positive HBsAg, anti-HCV or anti-HIV; positive pregnancy test or lactation.
  • 13. Positive drug screen or positive alcohol breath test.

Study Details

Locations

Poland

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