A multicentre, double-blind, randomised, placebo... — Clinical Trial Details

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).

Participants

Ages

18 – 65

Sexes

Male & Female

BMI

Psychosis History

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.

Company

Product

Legal

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

Detailed Description

Study Protocol

Preparation

Dosing

Locations

Integration

Therapeutic Protocol

Study Arms & Interventions

Esketamine low

Interventions

Esketamine mid

Interventions

Esketamine high

Interventions

Placebo

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details