Major depressive episodes (MDEs) associated with Bipolar I or Bipolar II Disorder (Bipolar Depression) with mixed features or major depressive disorder (MDD) with mixed features MedDRA version: 21.1 Level: LLT Classification code 10004936 Term: Bipolar depression System Organ Class: 100000004873 MedDRA version: 21.1 Level: LLT Classification code 10081270 Term: Major depressive disorder System Organ Class: 100000004873
Conditions
Interventions
Trade Name: CAPLYTA
Product Name: Lumateperone
Product Code: ITI-007
Pharmaceutical Form: Capsule
INN or Proposed INN: Lumateperone tosylate
CAS Number: 1187020-80-9
Current Sponsor code: Lumateperone
Sponsors
Intra-Cellular Therapies, Inc. (ITI)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements; 2. Male and female patients between the ages of 18 and 75 years, inclusive, at the start of screening; 3. Meets the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5) criteria for Bipolar I or Bipolar II Disorder with mixed features or MDD with mixed features, as confirmed by the Investigator or Sponsor-approved rater using the Mini-International Neuropsychiatric Interview (MINI) and meets all of the following 4 criteria: a. The start of the current MDE is at least 2 weeks but no more than 6 months prior to the Screening (Visit 1); b. Has at least moderate severity of illness, as measured by a rater-administered MADRS total score =24 and corresponding to a CGI-S score of = 4 at Screening (Visit 1) and Baseline (Visit 2); c. Has sufficient history and/or independent report (such as family member or outside practitioner) verifying that the current MDE is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning; d. Has a rater-administered YMRS total score between 4 and 16, inclusive, at Screening (Visit 1) and Baseline (Visit 2). 4. Has a body mass index (BMI) of 19–35 kg/m2, inclusive; 5. Either must agree to use highly effective methods of birth control (defined as those, alone or in combination, that result in a failure rate less than 1 percent per year when used consistently and correctly) for at least 2 weeks prior to randomization (starting with signing informed consent) through the end-of-study follow-up visit or must be of non-childbearing potential (defined as either permanently sterilized or, if female, post-menopausal; the latter is defined as at least 1 year with no menses without an alternative medical explanation); 6. In the opinion of the Investigator, the patient is willing and able to comply with study requirements, study visits, and to return to the clinic for follow-up evaluations as specified by the protocol. 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 420 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. The patient experiences a = 25% decrease in the rater-administered MADRS total score between Screening (Visit 1) and Baseline (Visit 2); 2. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during the course of his/her participation in the study or a. At Screening, the patient scores “yes” on Items 4 or 5 in the Suicidal Ideation section of the C-SSRS with reference to a 6-month period prior to screening; or b. At Screening, the patient has had 1 or more suicidal attempts with reference to a 2-year period prior to screening; or c. At Baseline, the patient scores “yes” on Items 4 or 5 in the Suicidal Ideation section of the C-SSRS with reference to Screening; or d. At Screening or Baseline, scores =4 on Item 10 (suicidal thoughts) on the rater-administered MADRS; or e. Considered to be an imminent danger to himself/herself or others; 3. The patient is pregnant or breast-feeding; 4. Within 12 months of screening, the patient has a confirmed DSM-5 psychiatric diagnosis other than Bipolar Disorder or MDD; 5. Patients who have experienced hallucinations, delusions, or any other psychotic symptomatology in the current depressive episode may be allowed as long as these symptoms are not attributable to a primary DSM-5 diagnosis other than Bipolar Disorder or MDD, as described in Exclusion Criterion #4; 6. The patient has been hospitalized for mania associated with Bipolar I Disorder within 30 days of screening; 7. The patient has received electroconvulsive therapy, vagal nerve stimulation, or repetitive trans-cranial magnetic stimulation within the last 5 years or received more than 1 course of electroconvulsive therapy during his/her lifetime. 8. For patients with bipolar depression, the patient has had at least 4 major depressive, manic, hypomanic, or mixed episodes during the previous year; 9. The patient is considered treatment-resistant, defined as having a lifetime history of treatment resistance (no remission) to = 2 treatments with medications approved for the treatment of MDD or medications approved for the treatment of bipolar depression at an adequate dose for an adequate duration; 10. The patient is currently receiving formal cognitive behavioral therapy, or plans to initiate such therapy during the study; 11. The patient presents with a lifetime history of epilepsy, seizure or convulsion, or electroencephalogram with clinically significant abnormalities, delirium, dementia, amnestic, or other cognitive disorder or significant brain trauma; 12. The patient has a positive test for drugs of abuse or alcohol at Screening or presents evidence of either withdrawal from or acute intoxication with cocaine, opiates, amphetamines, alcohol, barbiturates, or hallucinogens or similar compounds; 13. The patient has used 1 of the following agents under the specified conditions: a. Any previous exposure to lumateperone or exposure to any investigational product within 3 months of the baseline visit or participation in the past 4 years in >2 clinical studies of an investigational product with a central nervous system indication; b. Any strong or moderate cytochrome P450 3A4 inhibitor or inducer within 7 days prior to the baseline visit; c. Use of any short-acting anxiolytic medications within 1 week of Baseline/Visit 2 or of long-acting anxiolytics within 5 half-lives of the baseline visit; d. Drugs with known psychotropic properties or any non-psychotropic drugs with known or potentially significant
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy endpoint is the change from baseline to Day 43 in CGI-S score. The additional secondary efficacy endpoints are: • The proportion of patients who are treatment responders where response is defined as a = 50% decrease from baseline in MADRS total score at Day 43; • The proportion of remitters where remission is defined as a MADRS total score = 12 at Day 43; • By-visit mean changes from baseline in the MADRS total score; • By-visit mean changes from baseline in CGI-S score; • Change from baseline in MADRS individual item scores at each assessment time point, including Day 43.;Timepoint(s) of evaluation of this end point: As listed above. | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to confirm the efficacy of lumateperone 42 mg administered orally once daily compared with that of placebo as measured by mean change from baseline to Day 43 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score in patients with bipolar depression with mixed features or MDD with mixed features.;Secondary Objective: Key Secondary Objective: The key secondary objective of this study is to confirm the efficacy of lumateperone 42 mg administered orally once daily compared with that of placebo as measured by mean change from baseline to Day 43 in Clinical Global Impression Scale–Severity (CGI-S) score in patients with bipolar depression with mixed features or MDD with mixed features Safety Objective: The safety objective of this study is to determine the safety and tolerability of lumateperone administered orally once daily compared with that of placebo in patients with bipolar depression and MDD as assessed by adverse events (AEs); clinical laboratory results; vital sign measures; electrocardiogram (ECG) results; suicidality as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS); manic symptoms as assessed by the YMRS; and extrapyramidal symptoms (EPS) as assessed by Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson Angus Scale (SAS) scales;Primary end point(s): The primary efficacy endpoint is the change from baseline to Day 43 in MADRS total score.;Timepoint(s) of evaluation of this end point: baseline to Day 43 | — |
Countries
Bulgaria, Russian Federation, Serbia, Ukraine, United States
Contacts
Public ContactITI Clinical Trials
Intra-Cellular Therapies, Inc. (ITI)
Outcome results
None listed