The planned study is to determined the Esketamine’s efficacy (it's effectiveness and dose response) and pharmacokinetic properties (the fate of a substance in the body based on its concentration in the blood) and safety assessments (the occurrence of possible side effects) after multiple dose of inhaled Esketamine, compared to placebo in subject with treatment resistant bipolar depression.
- Conditions
- 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.Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2018-002669-20-PL
- Lead Sponsor
- Celon Pharma SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 88
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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method