A Study of CLE-100 (Oral Esketamine) in Addition to Standard Antidepressant Drug for Major Depressive Disorder - CLEO Study
- Conditions
- Adjunctive Treatment of Major Depressive Disorder
- Interventions
- Drug: placebo
- Registration Number
- NCT04103892
- Lead Sponsor
- Clexio Biosciences Ltd.
- Brief Summary
The clinical trial is a Phase 2, double-blind, randomized, placebo controlled study in Major Depressive Disorder (MDD) participants currently treated with antidepressant therapy. The objective of the study is to assess CLE-100 for the treatment of MDD in participants currently treated with standard antidepressant therapy.
- Detailed Description
CLEO study is performed in two parts (part A and Part B). The sponsor is currently recruiting only for the Part B of the study.
Part A will be an inpatient study to assess the safety, tolerability, and pharmacokinetics of CLE-100 (oral esketamine) in MDD participants currently treated with an antidepressant drug. It will include a screening phase (up to 35 days), a 1 week inpatient double-blind treatment phase and an outpatient post treatment safety follow-up phase of 1 week after last study drug administration.
Part B will be a study to assess the safety and efficacy of CLE-100 (oral esketamine) in MDD participants currently treated with an antidepressant drug with inadequate response to standard antidepressant therapy.
The participants will remain on their current antidepressant therapy with no dose change during the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 130
- Male or female between 18 to 60 years of age
- Primary diagnosis of MDD, without psychotic features according to DSM-5 and supported by the Mini International Neuropsychiatric Interview (MINI)
- MADRS score of at least 18 at Screening
- Treatment with stable dose of the current antidepressant therapy for at least 4 weeks for the current major depressive episode (MDE)
- Body mass index (BMI) between 18 and 40 kg/m2, inclusive
- Is able and competent to read and sign the informed consent form (ICF).
Part A -
- History of substance use disorder per DSM-5 criteria, except for tobacco use disorder
- History or current diagnosis of bipolar disorder, schizophrenia, schizoaffective disorders, binge eating disorder dementia, delirium, amnesia, or any other significant cognitive disorder
- Posttraumatic stress disorder, obsessive compulsive disorder, or any other mental disorder (including personality disorders)
- Has any medical condition for which an increase in blood pressure or intracranial pressure poses a serious risk
- Female of childbearing potential without appropriate contraceptive means, pregnant or breastfeeding
Part B - Inclusion Criteria:
- Male or female between 18 to 65 years of age
- Primary diagnosis of MDD without psychotic features according to DSM-5 and supported by the Mini International Neuropsychiatric Interview (MINI)
- MADRS score of at least 24 at Screening.
- At least 2 inadequate responses to antidepressant therapy (ADT) in the current Major Depressive Episode (MDE)
- Current MDE for at least 12 weeks
- BMI between 18 and 40 kg/m2, inclusive.
- Is able and competent to read and sign the ICF.
Part B - Exclusion Criteria:
- Inadequate response to more than 5 treatment courses of antidepressant medication therapy during the current MDE
- Current MDE for longer than 5 years.
-
- Has a current substance use disorder or history of any substance use disorder per DSM-5 criteria within 12 months prior to Screening, except for tobacco use disorder.
- Has a history or current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorders.
- Has dementia, delirium, amnesia, or any other significant cognitive disorder.
- Has posttraumatic stress disorder, obsessive compulsive disorder, or any other mental disorder (including personality disorders, eating disorders, etc.).
- Has any medical condition for which an increase in blood pressure or intracranial pressure poses a serious risk.
- Has been randomized in Part A of this study.
- Is a female of childbearing potential pregnant or breastfeeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A - Placebo placebo Part A: 1 oral tablet of Placebo once daily for 1 week. Part B - Placebo placebo Part B: 1 oral tablet of Placebo once daily for 4 weeks. Part B - CLE-100 (oral esketamine) CLE-100 Part B: 1 oral tablet of CLE-100 once daily for 4 weeks. Part A - CLE-100 (oral esketamine) CLE-100 Part A: 1 oral tablet of CLE-100 once daily for 1 week.
- Primary Outcome Measures
Name Time Method Part A - Four-items positive subscale from the Brief Psychiatric Rating Scale (BPRS) 7 days Four items of the BPRS will be administered to assess treatment-emergent psychotic symptoms. The BPRS is a widely used, clinician-administered instrument that involves 4 subscales: Negative Symptoms, Positive Symptoms, Manic-Hostility, and Anxiety/Depression. The 4-item Positive Symptoms subscale of the BPRS will be used to screen for potential psychiatric symptoms (suspiciousness, hallucinations, unusual thought content, and conceptual disorganization). Each item is scored on a 7-point scale (1 to 7). where a higher value represents a worse outcome. The 4 items BPRS total score ranges between 4 and 28.
Part A - Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) 7 days The MOAA/S will be used to measure treatment-emergent sedation. The MOAA/S is a widely used clinician-administered measure of alertness/sedation for clinical trials. The MOAA/S measures the alertness/sedation spectrum on a 6-point scale (0 to 5) based on verbal cues, where a higher value represents a better outcome.
Part A - Clinician-Administered Dissociative Symptoms Scale (CADSS) 7 days The CADSS will be administered to assess treatment-emergent dissociative symptoms. The CADSS is a 23-item instrument that is clinician-administered. Each item is scored on a 5-point scale (0 to 4. A higher value represents a worse outcome. The CADSS total score ranges between 0 and 92.
Part A - 20-item Physician Withdrawal Checklist (PWC-20) 14 days The PWC-20 is a clinician-administered assessment to evaluate potential withdrawal symptoms following cessation of the double-blind treatment. The PWC-20 is a shortened version of the original 35-item instrument used to determine withdraw symptoms in subjects following discontinuation of anxiolytics. The items are evaluated on a 4-point scale (0 to 3) where a higher value represents a worse outcome. The total score ranges between 0 to 60.
Part A - Cognitive function evaluated by Cogstate battery 7 days The Cogstate battery of cognitive tests will be used to measure psychomotor function, attention, visual learning, and working memory. The Cogstate battery will include the following tests: Detection Test, Identification Test, One Back Test, Groton Maze Test.
Part A - Frequency of adverse events 14 days Part A - Self-Administered Karolinska Sleepiness Scale 7 days The Karolinska Sleepiness Scale is a single-item, subjective, self-reported instrument measuring sleepiness on a 9-point Likert scale (1 to 9), where a higher value represents a worse outcome.
Part A - Columbia Suicide Severity Rating Scale (C-SSRS) 7 days The C-SSRS will be performed to assess suicidal ideation and behavior. The C-SSRS is an instrument used to assess suicide risk by measuring symptoms of suicidal ideation, self-harm, and suicidal behavior that is administered by trained personnel. The suicidal ideation is evaluated with a "yes/no" questionnaire and the suicidal behavior severity is scored on a 6-point scale (0 to 5) where a higher value represents a more severe behavior.
Part A - Pharmacokinetics of CLE-100 (Tmax) 7 days Time of maximum observed plasma concentration (Tmax)
Part A - Pharmacokinetics of CLE-100 (Cmax) 7 days Maximum observed plasma concentration (Cmax)
Part B - Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score 29 days The MADRS is a validated clinician-administered measurement of depression severity commonly used in clinical trials of depression treatments to select subjects and assess efficacy. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Part A - Digit Symbol Substitution Test (DSST) 7 days The DSST is a psychometric test assessing the integrity of executive function, processing speed, attention, spatial perception, and visual scanning, which are functions required for driving, and will be performed repeatedly. The DSST is a valid and sensitive instrument to evaluate cognitive dysfunction and changes in cognitive function. The DSST is a timed test taken by the subject and scored based on both the number of correct answers and the speed at which they were determined. The score ranges between 0 to 135.
Part A - Pharmacokinetics of CLE-100 (AUC) 8 days Area under the concentration curve
- Secondary Outcome Measures
Name Time Method Part B - Change from baseline in Sheehan Disability Scale (SDS) 29 days The SDS is a 3-item, self-completion instrument to assess functional impairments associated with work/school, social life and leisure activities, and family life and home responsibilities utilizing a 10-point scale.
Part B - Change from baseline in Symptoms of Depression Questionnaire (SDQ) score 29 days The SDQ is a 44-item self-report scale for the assessment of MDD that includes assessments for irritability, anger attacks, and anxiety symptoms. Higher scores represent a more severe condition.
Part B - Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score 15 days The MADRS is a validated clinician-administered measurement of depression severity commonly used in clinical trials of depression treatments to select subjects and assess efficacy. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Part B - Change from baseline in Clinical Global Impression - Severity (CGI-S) score 29 days The CGI-S is a well-known and frequently used clinician-administered instrument for the assessment of MDD that weighs the clinical impact of the identified symptom(s) on behavior and function. The CGI-S grades measures of psychopathology on a scale from 1 to 7.
Trial Locations
- Locations (46)
Clinical Site 112
🇺🇸Torrance, California, United States
Clinical Site 110
🇺🇸Las Vegas, Nevada, United States
Clinical Site 131
🇺🇸Baltimore, Maryland, United States
Clinical Site 120
🇺🇸Little Rock, Arkansas, United States
Clinical Site 126
🇺🇸Bentonville, Arkansas, United States
Clinical Site 129
🇺🇸Little Rock, Arkansas, United States
Clinical Site 121
🇺🇸Boston, Massachusetts, United States
Clinical Site 101
🇺🇸Marlton, New Jersey, United States
Clinical Site 124
🇺🇸Santa Ana, California, United States
Clinical Site 113
🇺🇸Oceanside, California, United States
Clinical Site 142
🇺🇸Santa Rosa, California, United States
Clinical Site 107
🇺🇸Hialeah, Florida, United States
Clinical Site 108
🇺🇸Miami Gardens, Florida, United States
Clinical Site 125
🇺🇸Lincoln, Nebraska, United States
Clinical Site 150
🇵🇷San Juan, Puerto Rico
Clinical Site 127
🇺🇸North Canton, Ohio, United States
Clinical Site 118
🇺🇸Philadelphia, Pennsylvania, United States
Clinical Site 106
🇺🇸Media, Pennsylvania, United States
Clinical Site 151
🇺🇸Dearborn Heights, Michigan, United States
Clinical Site 103
🇺🇸Boston, Massachusetts, United States
Clinical Site 116
🇺🇸Miami, Florida, United States
Clinical Site 136
🇺🇸Rockville, Maryland, United States
Clinical Site 148
🇺🇸Toms River, New Jersey, United States
Clinical Site 147
🇺🇸Draper, Utah, United States
Clinical Site 145
🇺🇸Denver, Colorado, United States
Clinical Site 122
🇺🇸Marietta, Georgia, United States
Clinical Site 140
🇺🇸Atlanta, Georgia, United States
Clinical Site 144
🇺🇸Plano, Texas, United States
Clinical Site 135
🇺🇸Bellevue, Washington, United States
Clinical Site 104
🇺🇸Decatur, Georgia, United States
Clinical Site 141
🇺🇸Anaheim, California, United States
Clinical Site 115
🇺🇸Bellflower, California, United States
Clinical Site 132
🇺🇸Lafayette, California, United States
Clinical Site 123
🇺🇸Riverside, California, United States
Clinical Site 139
🇺🇸Saint Louis, Missouri, United States
Clinical Site 143
🇺🇸Raleigh, North Carolina, United States
Clinical Site 102
🇺🇸Staten Island, New York, United States
Clinical Site 128
🇺🇸New York, New York, United States
Clinical Site 111
🇺🇸Hickory, North Carolina, United States
Clinical Site 138
🇺🇸Middleburg Heights, Ohio, United States
Clinical Site 114
🇺🇸Fort Worth, Texas, United States
Clinical Site 109
🇺🇸Houston, Texas, United States
Clinical Site 149
🇺🇸Missouri City, Texas, United States
Clinical Site 105
🇺🇸Orlando, Florida, United States
Clinical Site 137
🇺🇸Orlando, Florida, United States
Clinical Site 117
🇺🇸Oakland, California, United States