Efficacy and Safety of Lumateperone in Comparison to Quetiapine for the Treatment of Bipolar II Depression

Phase 3

Completed

• Conditions: Bipolar disorder, current episodedepressed, mild or moderate severity,

• Registration Number: CTRI/2023/10/058583
• Lead Sponsor: Sun Pharma Laboratories Limited SPLL

Brief Summary

This will be a multicenter, randomized, assessor-blind, parallel-group, phase III, active-controlled comparative study. The study will be conducted at approximately 10 to 15 centers from various parts of India, having qualified Investigators. The study will be initiated only after the receipt of Regulatory and Ethics committee (EC) approval. The patient will be screened only after obtaining written informed consent. Screening number will be allotted to every screened patient. At screening visit, the Investigator or his/her designee will provide prospective patient and his/her caregiver with a detailed description of the study objectives, study participation requirements, as well as potential health risks and benefits associated with study participation. After obtaining written informed consent (both patient and caregiver), study-specific screening.

During the study, assessments will be performed as mentioned in the Schedule of Assessment.

Patients will be asked about any adverse events experienced and any concomitant medications taken since last dose of treatment medication.

Patient’s health, any adverse event (AE) and signs of depression progression/worsening will be asked to the patients during the telephonic follow-up.

Patients will be provided with diary at Randomization visit to record details about study drug administration, concomitant medication and adverse events. Patients will be required to bring completed diary at each visit.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-10-21
• Last Update Posted: 2025-08-05

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 462

Inclusion Criteria

• 1. Patients with BMI of 18.5 to 35 Kg/m2 at Screening 2) Patients who meet the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5) criteria for Bipolar II Depressive Disorder by a MINI International Neuropsychiatric Interview (MINI) 3) Women of childbearing potential must be non-lactating and have a negative urine pregnancy test at Screening and Randomization visit and agree to use highly effective methods of contraception to prevent pregnancy from study entry till at least two weeks after the last dose of the study medication (such contraception may include hormonal birth control e.g., combined estrogen and progestogen containing [oral, intravaginal, or transdermal] or progesterone only [oral, injectable, or implantable] hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone releasing system OR bilateral tubal occlusion, vasectomized partner, or total sexual abstinence) [Note: Women with childbearing potential are defined as: those who are not (1) surgically sterile (bilateral oophorectomy, hysterectomy, or bilateral tubal ligation) or (2) post-menopausal.
• Post-menopausal woman will be defined as: Woman not using hormonal replacement therapy and have had at least 12 continuous months of natural (spontaneous) amenorrhea and be greater than 45 years of age] 4) Male patients must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period).
• No sperm donation is allowed during the study period.

Exclusion Criteria

• 1. The patient has a history within 12 months prior to screening, based on previous psychiatric evaluation or a confirmed diagnosis upon screening based on the DSM-5, of a psychiatric diagnosis other than Bipolar II Disorder, including: a) Bipolar I disorder b) Schizophrenia or other psychotic disorder c) Anxiety disorders such as panic disorder, general anxiety disorder, or post-traumatic stress disorder as a primary diagnosis (however, anxiety symptoms may be allowed, if secondary to Bipolar Disorder, provided these symptoms do not require current treatment) d) Feeding or eating disorder e) Primary diagnosis of obsessive-compulsive disorder f) Personality disorder g) Moderate or severe substance use disorder h) Any other psychiatric condition that has been the main focus of treatment 2) 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 the patient’s lifetime 3) The patient is considered a rapid cycler, defined by the occurrence of at least 6 major depressive, manic, hypomanic, or mixed episodes during the previous year 4) The patient is considered treatment-resistant 5) The patient is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study 6) 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 7) Patients using one of the following medications: a) Received Lumateperone anytime in the past b) Use of any strong or moderate cytochrome P450 3A4 inhibitor or inducer within 7 days prior to Randomization c) Use of any short-acting anxiolytic medications within 1 week prior to Randomization or of long-acting anxiolytics within 5 half-lives prior to Randomization d) Medication(s) with known psychotropic properties or any non-psychotropic medication(s) with known or potentially significant central nervous system effects within the last 28 days or 5 half-lives prior to Randomization, whichever is less, including, but not limited to: i.
• Sedative hypnotics (except zolpidem as needed, no more than 3 times per week, allowed during the screening period and the first 2 weeks of the treatment period) ii.
• Central opioid agonists/antagonists including tramadol iii.
• Anticonvulsants iv.
• Other psychiatric medications (e.g.: mood stabilizers, antipsychotics, antidepressants) v.
• Methotrexate vi.
• Any known 5-HT2A receptor antagonist or inverse agonist including but not limited to mianserin, mirtazapine, nefazodone, cyproheptadine, pimavanserin, or fluvoxamine vii.
• Immunosuppressants viii.
• Dietary supplements, medical foods, or pharmaceuticals containing Omega-3 fatty acids, melatonin, St. John’s Wort, kava kava, Vitamin B12, folate (no L-methylfolate in current episode), or valerian root.
• (Note: Daily multivitamin use is not an exclusion) 8) Patient with clinically significant cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, hematological, neurological, metabolic, psychiatric or other condition that might be detrimental to the patient if he or she participates in the study (in the opinion of the investigator) 9) Patient is unable to be safely discontinued from current antidepressant medication, mood stabilizers, anticholinergics, or other psychotropic medications (in the opinion of the investigator) 10) Patient is judged by the investigator to be inappropriate for the study 11) Patient who has not had a stable living environment for at least 3 months before the current exacerbating episode 12) Patient who is considered to be an imminent danger to themselves or others as judged by the investigator 13) Patients with any suicidal behavior as per investigator’s clinical judgment, OR had a suicide attempt 14) Patient with history of any cancer within 5 years prior to Screening 15) Patients with poorly controlled diabetes mellitus defined as glycated hemoglobin (HbA1c) >7% at Screening visit 16) Patients with any abnormal laboratory values that are judged to be clinically significant at the time of eligibility assessment [including, but not limited to: absolute neutrophil count (ANC) <2000/mm3, OR alanine aminotransferase (ALT) >3 x upper normal limit (ULN) OR aspartate aminotransferase (AST) >3 x ULN OR Alkaline phosphatase (ALP) >3 x ULN OR gamma glutamyl transpeptidase (GGT) >3 x ULN OR total bilirubin > 1.5 x ULN OR serum creatinine >1.5 x ULN OR creatinine phosphokinase (CPK) values >3 x ULN OR clinical significant out of range level of thyroid stimulating hormone (TSH)] 17) Prior history of neuroleptic malignant syndrome induced by any antipsychotic medication 18) Patient with surgical or medical condition that, in the judgment of the Investigator or Sponsor, could interfere with absorption, distribution, metabolism, or excretion of the study drugs 19) Patients with history of cataract or any other lens opacity 20) Patient with any surgery planned during the screening, treatment or follow-up periods 21) Patient with history of human immunodeficiency virus (HIV) and/or Hepatitis B and/or Hepatitis C 22) Patient with history of alcohol and/or any other substance abuse as per DSM-5 criteria within last 1 year 23) Patient with history of participation in another clinical trial in the past 6 months prior to screening or planning to participate during the study 24) Patient having hypersensitivity to the study drugs or drugs of similar chemical classes or to any of its excipients 25) Employee of the Sponsor, Investigator, or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members of the employees of Sponsor or the Investigator.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change from baseline in MADRS total score at the end of treatment at Day 42	Baseline & Day 42

Secondary Outcome Measures

Name	Time	Method
Change from baseline in MADRS total score at Days 14 & 28	Baseline, Day 14 & Day 28
Change from baseline in CGI-BP-S total score at Days 14, 28 & 42	Baseline & Days 14, 28 & 42
Change from baseline in CGI-BP-S mania sub-score at Days 14, 28 & 42	Baseline & Days 14, 28 & 42
Change from baseline in CGI-BP-S depression sub-score at Days 14, 28 & 42	Baseline & Days 14, 28 & 42
Change from baseline in CGI-BP-S overall bipolar illness sub-score at Days 14, 28 & 42	Baseline & Days 14, 28 & 42
Change from baseline in Quality of life enjoyment & satisfaction-short form questionnaire (Q-LES-Q-SF) total score at Days 14, 28 & 42	Baseline & Days 14, 28 & 42

Trial Locations

Locations (26)

Atmaram Child Care and Critical Care Hospital; 🇮🇳 Nagar, UTTAR PRADESH, India

B.J Medical College and Civil Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Dayanand Medical College & Hospital; 🇮🇳 Ludhiana, PUNJAB, India

Dhadiwal Hospital in coalition with Shreeji healthcare; 🇮🇳 Nashik, MAHARASHTRA, India

Gangoshri Hospital; 🇮🇳 Varanasi, UTTAR PRADESH, India

Global 5 Hospital; 🇮🇳 Thane, MAHARASHTRA, India

GMERS Medical College & Civil Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Government General Hospital; 🇮🇳 Guntur, ANDHRA PRADESH, India

Harshamitra Super Speciality Cancer Center and research institute; 🇮🇳 Tiruchirappalli, TAMIL NADU, India

Health 1 Super Speciality Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

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Atmaram Child Care and Critical Care Hospital

🇮🇳Nagar, UTTAR PRADESH, India

Dr Bhanu Pratap Singh Rathaur

Principal investigator

9450773088

drbhanuneurodm@gmail.com