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

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.

Participants

Ages

18 – 65

Sexes

Male & Female

BMI

Psychosis History

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.

Company

Product

Legal

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

Detailed Description

Study Arms & Interventions

Esketamine low dose

Interventions

Esketamine mid dose

Locations

Interventions

Esketamine high dose

Interventions

Placebo

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details