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Bipolar DepressionPhase 2NCT03965871

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

A Phase 2 study testing Esketamine DPI - low dose, Esketamine DPI - medium dose and Esketamine DPI - high dose in people with Bipolar Depression, run by Celon Pharma SA at 12 sites in Poland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Bipolar Depression
What is being tested?
Esketamine DPI - low dose, Esketamine DPI - medium dose and Esketamine DPI - high dose
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
88 participants
Where
12 sitesPoland
Study dates
28 Mar 2019to 19 Feb 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
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  • 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.

Who cannot join

  • 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,
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  • 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,
  • Blood drawn within 30 days prior to inclusion to the study,
  • 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.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Poland12 sites

  • Wojewodzki Szpital im. Jana Pawła II

    Bełchatów, 97-400

  • Wojewodzki Szpital dla Nerwowo i Psychicznie Chorych

    Bolesławiec, 59-700

  • Samodzielny Publiczny Psychiatryczny Zaklad Opieki Zdrowotnej

    Choroszcz, 16-070

  • Szpital Miejski

    Elblag, 82-300

  • Uniwersyteckie Centrum Kliniczne

    Gdansk, 80-952

  • Wojewodzki Szpital dla Nerwowo i Psychicznie Chorych

    Gmina Świecie, 86-100

  • Gornoslaskie Centrum Medyczne

    Katowice, 40-635

  • Specjalistyczny Psychiatryczny Zespol Opieki Zdrowotnej

    Lodz, 91-229

  • Pabianickie Centrum Medyczne

    Pabianice, 95-200

  • Mazowieckie Specjalistyczne Centrum Zdrowia

    Pruszków, 05-802

  • Mazowiecki Szpital i Centrum Diagnostyczne Allenort

    Warsaw, 03-185

  • Uniwersytecki Szpital Kliniczny

    Wroclaw, 50-556

Other trials in Poland

About this study

Official title: A Multicentre, Double-blind, Randomised, Placebo - Controlled Phase II Study to Assess Efficacy, Safety and Pharmacokinetics of Inhaled Esketamine in Subject With Treatment-resistant Bipolar Depression

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.

Read the detailed description

This is a randomized, multiple dose, placebo-controlled, double-blind, multicentre study of Esketamine DPI, inhalation powder delivered via dry powder inhaler (DPI) in participants with TRBD. There are 3 study phases: Screening phase, a two weeks double-blind treatment phase and a 6-week follow-up phase. Participants are to be randomized in 1:1:1:1 ratio to receive placebo or one of the three doses of Esketamine DPI. Participants from each group will receive different dosing sequences, consider as a single dose, corresponding to low, medium, high Esketamine dose or placebo. Participants will undergo one cycle of treatment consisting of four doses of Esketamine DPI or placebo over 14-day period. Participants safety will be monitored throughout the study.

Being tested
Esketamine DPI - low dose, Esketamine DPI - medium dose, Esketamine DPI - high dose, Placebo DPI
Medical subject headings
Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Esketamine DPI - low doseDrug

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

  • Esketamine DPI - medium doseDrug

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

  • Esketamine DPI - high doseDrug

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

  • Placebo DPIDrug

    Placebo DPI is to be administered via dry powder inhaler.

Study groups in NCT03965871
Study groupRoleWhat they receive
Esketamine low doseExperimentalParticipants are to receive four doses of Esketamine DPI administered over 14-day period (on Day 1, 4, 8 and 11).
Receives: Drug: Esketamine DPI - low dose
Esketamine medium doseExperimentalParticipants are to receive four doses of Esketamine DPI administered over 14-day period (on Day 1, 4, 8 and 11).
Receives: Drug: Esketamine DPI - medium dose
Esketamine high doseExperimentalParticipants are to receive four doses of Esketamine DPI administered over 14-day period (on Day 1, 4, 8 and 11).
Receives: Drug: Esketamine DPI - high dose
PlaceboPlacebo comparatorParticipants are to receive four doses of Placebo DPI administered over 14-day period (on Day 1, 4, 8 and 11).
Receives: Drug: Placebo DPI

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Day 1 and Day 14

Secondary outcomes (26)

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

    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.

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

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

    Clinical response is to be defined as greater than or equal to 50 % decrease in MADRS baseline score at Day 14 and every other timepoint.

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

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

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

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

    HDRS is a questionnaire used to rate the severity of depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss and somatic symptoms.HDRS consists of 17 questions with maximum 4-points scale. The higher HDRS total score, the more severe depression.

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

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

    Clinical remission, defined as MADRS total score less than or equal to 10.

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

  6. Time to relapse

    Relapse assessed for responders and remitters and defined when MADRS total score in 2 consecutive assessments after Day 14 exceeds 50% MADRS baseline total score value.

    Measured: Day 14 and week 3, 4, 5, 6, 7 and 8

  7. Change from baseline in Clinical Global Impression - Severity (CGI-S) score at Day 14 and every other timepoint

    CGI-S scale is a physician-rated scale that is designed to rate the severity of the patient's illness at the time of assessment. It is a 7-point assessment where 1 = normal (not at all ill) and 7 = among the most extremely ill patients.

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

  8. Change from baseline in Columbia Suicide Severity Rating Scale (C-SSRS) at Day 14 and every other timepoint

    C-SSRS is a suicide ideation rating scale created by researchers at Columbia University.

    Measured: Day 1, 14 and week 5, 8

  9. Change from baseline in the Clinician Administered Dissociative States Scale (CADSS) at each day of administration

    CADSS is a scale designed to assess dissociative symptoms. CADSS consists of 23 questions with 4-points scale, where 1=normal (not at all) and 4=Extremely. The higher CADSS total score, the more severe symptoms.

    Measured: up to 24 hours following the start of each administration

  10. Change from baseline in the Brief Psychiatric Rating Scale (BPRS) at each day of administration

    BPRS is a scale designed to rate psychotomimetic effects. BPRS consists of 18 questions with 7-points scale, from 1 (not present) to 7 (extremaly severe). The higher BPRS total score, the more severe effects.

    Measured: up to 24 hours following the start of each administration

  11. Severity of manic behaviour as assessed by the Young Mania Rating Scale (YMRS)

    Young Mania Rating Scale is a scale to rate manic-like mood elevation.YMRS consists of 11 items. The seven items have 4-points scale and four items have 8-points scale. The higher YMRS total score, the more severe manic symptoms.

    Measured: Day 0, 3, 7, 10, 14 and week 3, 4, 5, 6, 7, 8

  12. Potential withdrawal symptoms after Esketamine treatment, as measured by the 20-item Physician Withdrawal Checklist (PWC-20)

    PWC-20 is a method to assess discontinuation symptoms.

    Measured: Day 0, week 3, 4 and 5

  13. Potential Esketamine effect on cognition as measured by Montreal Cognitive Assessment (MoCA)

    MoCA is a screening assessment for detecting cognitive impairment.

    Measured: Day 0, week 4 and 8

  14. Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: up to 8 weeks

  15. Esketamine AUC0-24h - area under the plasma concentration - time curve from 0 to 24 h

    Measured: up to 24 hours following the start of first and fourth administration

  16. Esketamine Cmax - maximum plasma concentration

    Measured: up to 24 hours following the start of first and fourth administration

  17. Esketamine AUC0-inf - area under the plasma concentration - time curve from 0 to infinity

    Measured: up to 24 hours following the start of first and fourth administration

  18. Esketamine Kel - terminal elimination rate constant

    Measured: up to 24 hours following the start of first and fourth administration

  19. Esketamine t1/2 - plasma elimination half-life

    Measured: up to 24 hours following the start of first and fourth administration

  20. Esketamine Tmax - time to reach maximum concentration in plasma

    Measured: up to 24 hours following the start of first and fourth administration

  21. Esnorketamine AUC0-24h - area under the plasma concentration - time curve from 0 to 24 h

    Measured: up to 24 hours following the start of first and fourth administration

  22. Esnorketamine Cmax - maximum plasma concentration

    Measured: up to 24 hours following the start of first and fourth administration

  23. Esnorketamine Tmax - time to reach maximum concentration in plasma

    Measured: up to 24 hours following the start of first and fourth administration

  24. Changes between predose and postdose values for each administration in hematology and biochemistry

    Measured: up to 6 weeks

  25. Changes between predose and postdose values for each administration in vital signs (heart rate, blood pressure, respiratory rate) and urinalysis

    Measured: up to 8 weeks

  26. Changes between predose and postdose values for each administration in SpO2 (blood oxygen saturation)

    Measured: up to 2 hours following the start of each administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2019
  2. Study start28 Mar 2019
  3. Primary completion3 Jan 2021
  4. Study completion19 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
88 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03965871
Sponsor's protocol ID
03KET2018
Status last verified
Mar 2021
First submitted
21 May 2019
Last updated
19 Mar 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 34510411

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Esketamine DPI - low dose, Esketamine DPI - medium dose and Esketamine DPI - high dose in people with Bipolar Depression, run by Celon Pharma SA at 12 sites in Poland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at Day 14 (time frame: Day 1 and Day 14). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03965871, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2021.

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