CTRI/2023/10/058583 [Registered on: 12/10/2023] Trial Registered Prospectively
Last Modified On:
08/05/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
Efficacy and Safety of Lumateperone in Comparison to Quetiapine for the Treatment of Bipolar II Depression
Scientific Title of Study
A Multicenter, Randomized, Assessor-blind, Parallel-group, Phase III, Active-control Comparative Study to Evaluate the Efficacy and Safety of Lumateperone in Comparison to Quetiapine for the Treatment of Bipolar II Depression
Trial Acronym
BOLD-IN
Secondary IDs if Any
Secondary ID
Identifier
ICR/22/004 version 2 Dated 30/JUN/2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Pravin Ghadge
Designation
Associate Vice President & Head - India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun House, Plot No. 201 B/1, Western Express Highway, Goregaon (E), Mumbai, Maharashtra, India
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
pravin.ghadge@sunpharma.com
Details of Contact Person Scientific Query
Name
Dr Shruti Saha
Designation
Manager – India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun House, Plot No. 201 B/1, Western Express Highway, Goregaon (E), Mumbai, Maharashtra, India
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
shruti.saha@sunpharma.com
Details of Contact Person Public Query
Name
Sucheta A Pandit
Designation
Deputy General Manager - India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun House, Plot No. 201 B/1, Western Express Highway, Goregaon (E), Mumbai, Maharashtra, India
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
Sucheta.Pandit@sunpharma.com
Source of Monetary or Material Support
Sun Pharma Laboratories Limited.
Sun House, 201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400063
Primary Sponsor
Name
Sun Pharma Laboratories Limited SPLL
Address
Sun Pharma Laboratories Limited, Sun House, 201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400063
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
Sun Pharma Laboratories Limited
Sun Pharma Advanced Research Centre (SPARC), Tandalja, Vadodaria -390012, Gujarat, India
F-2/D-1,1st floor, Main road, Sector-9, Vashi, Navi Mumbai - 400703, Maharashtra, India. Thane MAHARASHTRA
9764044079
Prashantdasud@gmail.com
Dr Pradhyuman Jeshingbhai Chaudhary
GMERS Medical College & Civil Hospital
Department of Psychiatry, 1st floor, OPD block, Sola gram road, behind gujarat high court, Ahmedabad-380060, Gujarat, India. Ahmadabad GUJARAT
9825411772
drpradhyuman@gmail.com
Dr Neeli Uma Jyothi
Government General Hospital
Department of Psychiatry, Room No. 117, Guntur-522001.
Andhra Pradesh - India Guntur ANDHRA PRADESH
9440062160
neelijyothi31@gmail.com
Dr Anbazhagan Ramaraju
Harshamitra Super Speciality Cancer Center and research institute
Psychiatric department, Room no 2 0.101/4A, Mathur Panchayat Road, Trichy –Madurai Highway Nagamangalam, Trichy-620012. Tiruchirappalli TAMIL NADU
9790180751
dr.anbu87@gmail.com
Dr Shah Fenil Atul Bhai
Health 1 Super Speciality Hospital
Room No 5, first Floor, Near Venitian Villa, Shilaj Circle, S.P Ring Rd, Thaltej, Ahemadabad, Gujrat-380059 Ahmadabad GUJARAT
9409009484
drfenil.cr@gmail.com
Dr Sujit Sarkhel
IPGMEandR and SSKM Hospital
Professor Room, 3rd Floor, Institute of Psychiatry building, Institute of Psychiatry block, IPGME&R and SSKM Hospital, Kolkata - 700020, West Bengal, India Kolkata WEST BENGAL
9836074700
sujitsarkhel@gmail.com
Dr Parth Singh Meena
Jawahar Lal Nehru Medical College
Department of Psychiatry, Kala Bagh, Ajmer-305001, Rajasthan. Ajmer RAJASTHAN
8118877284
Doctor.parth@outlook.com
Dr Sameer Belvi Mangalwedhe
Karnataka Institute of medical Sciences
Department of Psychiatry, Vidyanagar, Hubli-580022, Karnataka, India. Dharwad KARNATAKA
9845612224
sameerbelvi@gmail.com
Dr Dhananjay Chaudhari
LLR Hospital (Hallet Hospital), GSVM Medical College
V. S. General Hospital_IEC_Riddhi Medical Nursing Home
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: F313||Bipolar disorder, current episodedepressed, mild or moderate severity,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Lumateperone Capsules 42 mg
One capsule should be taken orally once daily till 6 weeks.
Comparator Agent
Quetiapine Tablets 50 mg - 300 mg
One tablet to be taken orally once daily till 6 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
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.
ExclusionCriteria
Details
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.
Method of Generating Random Sequence
Permuted block randomization, fixed
Method of Concealment
Not Applicable
Blinding/Masking
Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
Change from baseline in MADRS total score at the end of treatment at Day 42
Baseline & Day 42
Secondary Outcome
Outcome
TimePoints
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
Target Sample Size
Total Sample Size="462" Sample Size from India="462" Final Enrollment numbers achieved (Total)= "462" Final Enrollment numbers achieved (India)="462"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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.