Eketamine, ketamine’s enantiomer, is designed for use in tretment resistant depression, both unipolar and bipolar. Many publications have demonstrated the effect of ketamine/esketamine (mainly administered intravenously) in treatment resistant depression, with effect seen after an hour after administration. The therapeutic effect after single administration can last up to one week. In addition, it was shown that ketamine can reduce the intensity of suicidal thoughts.
Conditions
Sponsors
Celon Pharma SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Gender: female or male, 2. Age: 18 – 65 years old, inclusive, on the day of Screening, 3. Subject must meet Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria for depressive episode in Bipolar Disorder type I or II, without psychotic features, based upon clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (MINI), 4. Subject must have in Montgomery Åsberg Depression Rating Scale (MADRS) total score of greater than or equal to (=) 24 at Screening and predose on Day 1, 5. Subject 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. Sufficient duration and dose are understood as a treatment regimen dose in the therapeutic range (for lithium/valproate treatment also therapeutic concentration in the blood) and treatment duration of at least 6 weeks, 6. Subject in the last mood stabilizing treatment regimen is to be administered at least one of the medication listed in the table 9 (details in protocol Section IX.2. Tab.9.), 7. Subject’s last mood stabilizing treatment regimen is to be without antidepressant drugs from the class: SSRI, SNRI, TCA, MAOI or NaSSA, 8. Subject must be on stable mood stabilizing treatment regimen (listed in protocol Section IX.2. Tab.9.), remain non-responsive to it and continue the treatment from Screening to at least the duration of the double-blind treatment phase (Day 14), 9. Subject’s other drugs taken as a standard treatment for bipolar disorder (e.g. aripiprazole), 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, 10. As part of standard of care treatment, subject agrees to be hospitalized voluntarily for a period of 12 h before first IMP administration and until the end of treatment phase on Day 14., 11. Subject must be medically stable on the basis of clinical laboratory tests, physical examination, vital signs, 12-lead ECG (with QTcB interval analysis) performed at Screening. It is up to Investigator discretion to include subject with abnormalities or deviations from normal judged by Investigator as not clinically significant, 12. Subject is to be comfortable with self-administration of inhalatory medication and able to follow investigator instructions, 13. Subject agrees to blood sample collection for DNA analysis, 14. Able to sign informed consent after receiving information about the trial, 15. Ability and willingness to comply with the requirements and restrictions of the study protocol, 16. Subject of childbearing potential willing to use acceptable forms of contraception: complete abstinence from sexual intercourses or barrier method of spermicide (condom, diaphragm) or intrauterine device or hormonal contraceptive since at least Screening evaluations for male subjects and since at least 4 weeks before Screening for female subjects. Subjects are furthermore willing to use it for at least 90 days (males) or 30 days (females) after examination at the end of the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 88 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this ag
Exclusion criteria
Exclusion criteria: 1. Subject has a current DSM-5 diagnosis, according to Mini International Neuropsychiatric Interview (MINI), of any other than BD disorder including: psychotic, personality disorders, intellectual disability, post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), major depressive disorder (MDD), 2. Subject has a BD with a rapid-cycling course (= 4 episodes per year), 3. Subject has in Young Mania Rating Scale (YMRS) total score of greater than (?) 12 at Screening and every other assessment, 4. Subject 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, 5. Subject 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, 6. Subject has uncontrolled hypertension (systolic blood pressure or diastolic blood pressure) despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment at Screening and/or on Day 0 and/or on Day 1 before IMP administration, 7. Upper respiratory tract and/or chest infection and/or inflammation within 2 weeks preceding the first IMP administration and during the treatment phase, 8. Subject participated in other clinical trial, where at least one dose of study drug was administered, within 90 days preceding the Screening, 9. Known allergy or hypersensitivity, intolerance or contraindication to Esketamine/ketamine or its derivatives and/or to any study product excipients, 10. Blood drawn within 30 days prior to inclusion to the study (more or equal to 300 mL), 11. History of drug, alcohol, chemical, sedatives or sleeping medications abuse or dependence (except nicotine or caffeine) within 2 years prior to Screening, 12. Lifetime abuse or dependence on ketamine or phencyclidine, 13. Positive results of HBsAg, anti-HCV or anti-HIV test, 14. Positive results from pregnancy test for female subjects, 15. Lactation in female subjects, 16. Positive drug screen (except benzodiazepines evaluation during follow-up) or alcohol breath test, 17. Inability or unwillingness to provide written informed consent, 18. For any reason the subject is considered by the study Investigator to be an unsuitable candidate to participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to determine the efficacy and dose response of Esketamine, administered by inhalation from Dry Powder Inhaler, compared with placebo, in subjects with treatment resistant bipolar depression, as assessed by change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Day 14 of treatment phase.;Secondary Objective: -To evaluate effect of inhaled Esketamine in TRBD subjects, compared to placebo -To evaluate durability of Esketamine’s antidepressant response in TRBD subjects defined by ‘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. Time to relapse is to be computed from Day 14 to the first of two assessments exceeding 50% MADRS baseline total score value), -To investigate safety and tolerability of inhaled Esketamine in TRBD subjects, -To evaluate the pharmacokinetic properties of inhaled Esketamine (and Esnorketamine) in TRBD subjects. Exploratory objectives: -to investigate correlation of Val66Met BDNF polymorphism with Esketamine antidepressive efficacy in subjects with TRBD. -to investigate levels of inflammatory cytokines as Esketamine’s efficacy predictive biomarkers. -to measure Esketamine’s metabolites concentrations – hydroxynorketamines.;Primary end point(s): Change from baseline (day 1, predose) in MADRS total score at Day 14 (3 days post last dose);Timepoint(s) of evaluation of this end point: at the end of treatment phase on Day 14 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline (Day 1, predose) in MADRS total score at each other than Day 14 timepoint, • Clinical response, defined as greater than or equal to 50 % decrease in MADRS baseline score (day 1, predose) at Day 14 and every other timepoint. Subject is to be considered as a responder while having clinical response on Day 14, • Onset of clinical response (= 50 % decrease in baseline MADRS score) that was sustained through the end of the 2-week, double-blind, treatment phase, • Change from baseline (Day 1, predose), in depression severity, measured by Hamilton Depression Rating Scale (HDRS) at every timepoint, • Clinical remission, defined as MADRS total score less than or equal to 10. Subject is to be considered as a remitter while having clinical remission on Day 14, • 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. Time to relapse is to be computed from Day 14 to the first of two assessments exceeding 50% MADRS baseline total score value), • Change from baseline (Day 1, predose) in Clinical Global Impression - Severity (CGI-S) score at Day 14 and every other timepoint, • Change from baseline (Day 1, predose) in Columbia Suicide Severity Rating Scale (C-SSRS) at Day 14 and every other timepoint, • Change from baseline (Day 1, predose) in the Clinician Administered Dissociative States Scale (CADSS) at each day when IMP is administered (predose, 45 min, 2 h, 4 h and 24 h following the start of dosing), • Change from baseline (Day 1, predose) in the Brief Psychiatric Rating Scale (BPRS) at each day when IMP is administered (predose, 45 min, 2 h, 4 h and 24 h following the start of dosing), • Changes between predose and postdose values for each IMP administration in heart rate, blood pressure, respiratory rate, blood oxygen saturation (SpO2) at each timepoint, and clinically significant results in | — |
Countries
Poland
Contacts
Public ContactClinical Development Leader
Celon Pharma SA
Outcome results
None listed