Efficacy, Safety and Pharmacokinetic Study of Inhaled Esketamine in Treatment-resistant Bipolar Depression

NCT03965871 | Completed Phase 2

• 1 other identifier: 03KET2018
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of the study is to determine the efficacy, safety and pharmacokinetics of inhaled Esketamine in participants with treatment-resistant bipolar depression (TRBD). The study is to determine the efficacy and dose response of three Esketamine doses, compared with placebo.

Conditions

Bipolar Depression

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at Day 14

  The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The test consists of 10 items, each scored from 0 (symptoms not present or normal) to 6 (severe or continuous presence of the symptoms). Total score is 60. The higher MADRS total score, the more severe depression.

  Day 1 and Day 14

Secondary Outcomes (26)

• Change from baseline in MADRS total score at each other than Day 14 timepoint

  Day 1, 2, 4, 5, 8, 9, 11, 12 and week 3, 4, 5, 6, 7 and 8

• Number of participants with clinical response (>= 50% decrease in MADRS baseline score)

  Day 1, 2, 4, 5, 8, 9, 11, 12, 14 and up to 6 weeks after the treatment phase

• Onset of clinical response that was sustained through the end of the 2-week, double-blind, treatment phase

  Day 1, 2, 4, 5, 8, 9, 11, 12, 14

• Change from baseline in depression severity, measured by Hamilton Depression Rating Scale (HDRS) at every timepoint

  Day 1, 2, 4, 5, 8, 9, 11, 12, 14 and week 3, 4, 5, 6, 7 and 8

• Number of participants with clinical remission (MADRS total score <= 10)

  Day 1, 2, 4, 5, 8, 9, 11, 12, 14 and up to 6 weeks after the treatment phase

Study Arms (4)

Esketamine low dose

EXPERIMENTAL

Participants are to receive four doses of Esketamine DPI administered over 14-day period (on Day 1, 4, 8 and 11).

Drug: Esketamine DPI - low dose

Esketamine medium dose

EXPERIMENTAL

Participants are to receive four doses of Esketamine DPI administered over 14-day period (on Day 1, 4, 8 and 11).

Drug: Esketamine DPI - medium dose

Esketamine high dose

EXPERIMENTAL

Participants are to receive four doses of Esketamine DPI administered over 14-day period (on Day 1, 4, 8 and 11).

Drug: Esketamine DPI - high dose

Placebo

PLACEBO COMPARATOR

Participants are to receive four doses of Placebo DPI administered over 14-day period (on Day 1, 4, 8 and 11).

Drug: Placebo DPI

Interventions

Esketamine DPI - low dose DRUG

Esketamine DPI is to be administered via dry powder inhaler. Each dose correspond to low Esketamine dose.

Esketamine low dose

Esketamine DPI - medium dose DRUG

Esketamine DPI is to be administered via dry powder inhaler. Each dose correspond to medium Esketamine dose.

Esketamine medium dose

Esketamine DPI - high dose DRUG

Esketamine DPI is to be administered via dry powder inhaler. Each dose correspond to high Esketamine dose.

Esketamine high dose

Placebo DPI DRUG

Placebo DPI is to be administered via dry powder inhaler.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Gender: female or male,
• Age: 18 - 65 years old, inclusive, on the day of Screening,
• Participant must meet Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria for depressive episode in Bipolar Disorder (BD) type I or II, without psychotic features, confirmed by the Mini International Neuropsychiatric Interview (MINI),
• Participant must have in Montgomery-Asberg Depression Rating Scale (MADRS) total score of \>= 24 at Screening and predose on Day 1,
• Participant is treatment resistant in the current episode of depression, defined as having an inadequate response to at least 2 adequate mood stabilizing treatment regimens administered for the sufficient duration and dose and administered in the current episode of depression,
• Participant in the last mood stabilizing treatment regimen is to be administered at least one of the medication listed in the protocol,
• Participant's last mood stabilizing treatment regimen is to be without antidepressant drugs from the class: SSRI, SNRI, TCA, MAOI or NaSSA,
• Participant must be on stable mood stabilizing treatment regimen (listed in the protocol), remain non-responsive to it and continue the treatment from Screening to at least the duration of the double-blind treatment phase,
• Participant's other drugs taken as a standard treatment for bipolar disorder, but not for depressive episode treatment, are to be allowed and may be continued through the study and it's administration is up to Investigator discretion,
• Participant agrees to be hospitalized voluntarily for a period of 12 h before first administration and until the end of treatment phase on Day 14,
• Participant must be medically stable on the basis of clinical laboratory tests, physical examination, vital signs, 12-lead ECG,
• Participant agrees to blood sample collection for DNA analysis,
• Participant of childbearing potential willing to use acceptable forms of contraception.

You may not qualify if:

• Participant has a current DSM-5 diagnosis, according to MINI, of any other than BD disorder,
• Participant has a BD with a rapid-cycling course (≥ 4 episodes per year),
• Participant has in Young Mania Rating Scale (YMRS) total score of greater than 12 at Screening and every other assessment,
• Participant has suicidal ideation in MADRS 'suicidal thoughts' subscale score greater or equal to 2 and/or in C-SSRS score greater or equal to 4 at Screening and/or has a history of suicidal thoughts within 6 months prior to Screening and/or history of suicidal attempt within 1 year prior to Screening,
• Participant has a history or current signs and symptoms of chronic obstructive pulmonary disease (COPD), asthma, liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, neurologic, rheumatologic or metabolic disturbances that are uncontrolled with medication change during last three months before Screening and/or that could influence the present general health condition at the Investigator's discretion,
• Participant has uncontrolled hypertension,
• Upper respiratory tract and/or chest infection and/or inflammation within 2 weeks preceding the first administration and during the treatment phase,
• Participant took part in other clinical trial within 90 days preceding the Screening,
• Known allergy or hypersensitivity, intolerance or contraindication to Esketamine/ketamine or its derivatives and/or to any study product excipients,
• History of drug, alcohol, chemical, sedatives or sleeping medications abuse or dependence (except nicotine or caffeine) within 2 years prior to Screening,
• Lifetime abuse or dependence on ketamine or phencyclidine,
• Positive results from pregnancy test for female participants,
• Lactation in female participants,
• Positive drug screen (except benzodiazepines evaluation during follow-up) or alcohol breath test.

Sponsors & Collaborators

• Celon Pharma SA: lead
• National Center for Research and Development, Poland: collaborator

Study Sites (12)

Wojewodzki Szpital im. Jana Pawła II

Bełchatów, 97-400, Poland

Location

Wojewodzki Szpital dla Nerwowo i Psychicznie Chorych

Bolesławiec, 59-700, Poland

Location

Samodzielny Publiczny Psychiatryczny Zaklad Opieki Zdrowotnej

Choroszcz, 16-070, Poland

Location

Szpital Miejski

Elblag, 82-300, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Wojewodzki Szpital dla Nerwowo i Psychicznie Chorych

Gmina Świecie, 86-100, Poland

Location

Gornoslaskie Centrum Medyczne

Katowice, 40-635, Poland

Location

Specjalistyczny Psychiatryczny Zespol Opieki Zdrowotnej

Lodz, 91-229, Poland

Location

Pabianickie Centrum Medyczne

Pabianice, 95-200, Poland

Location

Mazowieckie Specjalistyczne Centrum Zdrowia

Pruszków, 05-802, Poland

Location

Mazowiecki Szpital i Centrum Diagnostyczne Allenort

Warsaw, 03-185, Poland

Location

Uniwersytecki Szpital Kliniczny

Wroclaw, 50-556, Poland

Location

Related Publications (1)

• Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 2021 Sep 12;9(9):CD011612. doi: 10.1002/14651858.CD011612.pub3.

  PMID: 34510411 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 29, 2019
• Study Start: March 28, 2019
• Primary Completion: January 3, 2021
• Study Completion: February 19, 2021
• Last Updated: March 19, 2021

Record last verified: 2021-03

Locations

PL (12)