CTRI/2023/05/052793 [Registered on: 17/05/2023] Trial Registered Prospectively
Last Modified On:
22/05/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
Safety and Efficacy of Cariprazine Capsules in Adult Patients with Schizophrenia (a disorder that affects a persons ability to think, feel and behave clearly) and Acute Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder (mood swings that include emotional highs and lows)
Scientific Title of Study
A Prospective, Multi-centre, Single-arm, Phase IV Study to Assess the Safety and Efficacy of Cariprazine Capsules in Adult Patients with Schizophrenia and Acute Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ICR/21/014, Version No. 1.0; 01/OCT/2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Pravin Ghadge
Designation
AVP Head-India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited, Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400 063, 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 Pharma Laboratories Limited, Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400 063, Maharashtra, India.
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
shruti.saha@sunpharma.com
Details of Contact Person Public Query
Name
Nilesh Kadam
Designation
Senior Manager
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited,
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
nilesh.kadam@sunpharma.com
Source of Monetary or Material Support
Sun Pharmaceutical Industries Limited
Primary Sponsor
Name
Sun Pharmaceutical Industries Limited
Address
Sun Pharmaceutical Industries Limited
Sun House, 201 B/1, Western Express Highway,
Goregaon ( E),Mumbai 400 063
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
Not Applicable
Not Applicable
Countries of Recruitment
India
Sites of Study
No of Sites = 7
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Susanta Kumar Padhy
AIIMS
AIIMS, Bhubaneshwar - 1st Floor, Block - B, Room No. 123- 127, Department of Psychiatry, All India Institute of Medical Sciences, Sijua, Patra pada, Bhubaneshwar – 751019, Odisha. Khordha ORISSA
9463895852
susanta.pgi30@yahoo.in
Dr Rakesh Khandelwal
Apex Hospital
Apex Hospital – OPD 30, Basement, Department of Psychiatry, Apex Hospitals Pvt. Ltd., SP 4 & 6, Malviya Nagar, MIA Jaipur - 302 017 Jaipur RAJASTHAN
941404756
drrakesh@live.com
Dr Prashant Laxmanrao Dasud
Calida Psychiatric Hospital
Calida Psychiatric Hospital-REHAB – OPD No. 01, Ground Floor, Department of Psychiatry, 55/1/a, Tata Road, Village Bhaliwadi, Post Gaulwadi, Karjat, Raigad, Maharashtra-410201 Raigarh MAHARASHTRA
9764044079
prashantdasud@gmail.com
Dr Nishanth Vamana
Excel Hospital
Excel Hospital - Room No. 104, First Floor, Department of Psychiatry, Excel Hospital, 1-5-56/29, Old Alwal Rd, beside Bharat Petroleum, Near IG Statue, Banda Basti, Old Alwal, Alwal, Secunderabad, Telangana 500010 Hyderabad TELANGANA
9948027129
vemananishanth12@gmail.com
Dr Dhananjay Chaudhari
GSVM Medical College
GSVM Kanpur – HOD room, ground floor, Department of Psychiatry, GSVM Medical College, Swaroop Nagar Kanpur, 208002, U.P. India. Kanpur Dehat UTTAR PRADESH
9336049009
georgiandc@gmail.com
Dr Charan Singh Jilowa
JLN Hospital
JLN Hospital – Ground floor Medical College building, Department of Research, Jawahar Lal Nehru Medical College, Kala Bagh, Ajmer-305001, Rajasthan, India Ajmer RAJASTHAN
818877284
clinical.JLN@gmail.com
Dr Shri Gopal Goyal
S.P. Medical College & A.G. of Hospitals
S. P. Medical College – Ground floor/ 1st floor, Clinical Research unit, DIMHANS, S.P. Medical College & A. G. of Hospitals, Bikaner, Rajasthan – 334003 Bikaner RAJASTHAN
One capsule should be taken orally once daily for 42 days and can be taken with or without food.
Comparator Agent
Not Applicable
Not Applicable
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
Patients of either gender aged between 18 to 65 years both inclusive who agree to provide written informed consent
Patients eligible to continue as outpatients based on the opinion of the Investigator; and must have a caregiver to ensure treatment compliance
Body mass index between 18 and 40 kg per m2eter square both inclusive
Subjects willing to discontinue all prohibited medications to meet protocol required washouts prior to enrolment and during the treatment period and patients on psychotropic medications other than the allowed medication will undergo a washout period
Women of childbearing potential must have a negative urine pregnancy test before study entry 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
Male patients must have had a successful vasectomy confirmed azoospermia or they and their female partners must meet the criteria above i e not of childbearing potential or practicing highly effective contraception throughout the study period No sperm donation is allowed during the study period
Patients with diagnosis of schizophrenia as per Diagnostic and Statistical Manual of Mental Disorders criteria at least 1 year prior to enrolment
Patients with a diagnosis of bipolar I disorder manic or mixed type with or without psychotic symptoms based on the DSM V Diagnosis should be confirmed by the Mini International Neuropsychiatric Interview and a history of at least one previous manic episode with or without mixed features with manic symptoms
Patients with Montgomery–Asberg Depression Rating Scale Total score <18 at the time of screening and enrolment
ExclusionCriteria
Details
Patients with treatment-resistant schizophrenia over the last 2 years, defined as little or no symptomatic response to at least 2 antipsychotic trials of an adequate duration (at least 6 weeks) and at a therapeutic dose range (specifically for Schizophrenia)
Patients with treatment resistant Bipolar I disorder (treatment with clozapine in a dose of > 50 mg/day in the past 2 years), or patients considered unresponsive to clozapine or who are only responsive to clozapine (specifically for Bipolar I disorder)
Four or more episodes of a mood disturbance depression mania hypomania or mixed state) within the 12 months before screening (specifically for Bipolar I disorder)
Patients who are Rapid cyclers (with more than 6 episodes in the previous year (specifically for Bipolar I disorder)
Patients with a history of DSM-5 diagnosis of bipolar I disorder (for schizophrenia), and schizophrenia (for Bipolar I disorder), schizoaffective disorder, major depressive disorder, Bipolar II disorder, attention-deficit/hyperactivity disorder, delirium, dementia, amnestic, or other cognitive disorders; known or suspected borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder within 3 months prior to screening
Patients who require hospitalization as judged by the investigator at time of enrolment
Patients on antipsychotic medication(s) that require washout period (as mentioned in the Section 10.6) that is not feasible for the patient as per the investigator’s judgment
Patients on Cytochrome (CYP) 3A4 inducer(s) or CYP2D6 inhibitors
Patients with treatment-resistant schizophrenia over the last 2 years, defined as little or no symptomatic response to at least 2 antipsychotic trials of an adequate duration (at least 6 weeks) and at a therapeutic dose range (specifically for Schizophrenia)
Patients with treatment resistant Bipolar I disorder (treatment with clozapine in a dose of > 50 mg/day in the past 2 years), or patients considered unresponsive to clozapine or who are only responsive to clozapine (specifically for Bipolar I disorder)
Four or more episodes of a mood disturbance depression mania hypomania or mixed state) within the 12 months before screening (specifically for Bipolar I disorder)
Patients who are Rapid cyclers (with more than 6 episodes in the previous year (specifically for Bipolar I disorder)
Patients with a history of DSM-5 diagnosis of bipolar I disorder (for schizophrenia), and schizophrenia (for Bipolar I disorder), schizoaffective disorder, major depressive disorder, Bipolar II disorder, attention-deficit/hyperactivity disorder, delirium, dementia, amnestic, or other cognitive disorders; known or suspected borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder within 3 months prior to screening
Patients who require hospitalization as judged by the investigator at time of enrolment
Patients on antipsychotic medication(s) that require washout period (as mentioned in the Section 10.6) that is not feasible for the patient as per the investigator’s judgment
Patients on Cytochrome (CYP) 3A4 inducer(s) or CYP2D6 inhibitors
Patients with hypothyroidism or hyperthyroidism unless condition has been stabilized with medications for at least within the past 3 months as per Investigator discretion or an abnormal result for free T4 at screening
Patients with severe hepatic impairment Child Pugh score between 10 and 15 and severe renal impairment
Electroconvulsive therapy in the 3 months before enrolment or previous lack of response to electroconvulsive therapy
Previous treatment with vagus nerve stimulation or transcranial magnetic stimulation within 6 months before enrolment
At imminent risk of injuring self or others or causing significant damage to property as judged by the Investigator
Suicide risk as determined by the following criteria a suicide attempt within the past 2 years b significant risk as judged by the Investigator based on the psychiatric interview or information collected in the Columbia Suicide Severity Rating Scale
Patients with documented disease of the central nervous system that can interfere with the trial assessments including but not limited to stroke tumor Parkinsons organic brain disease seizure disorder except for febrile convulsions during infancy chronic infection or neurosyphilis or patients who have suffered a traumatic brain injury resulting in significant impairment
Patients with clinically significant cardiovascular, hepatic, renal, metabolic including uncontrolled type II diabetes mellitus HbA1C more than 7% hematological immunological pulmonary or gastrointestinal disorders as judged by the investigator
Patients with concurrent medical conditions that in the judgment of the Investigator might interfere with the conduct of the trial confounded the interpretation of the trial results or endangered the patients well being
Patients with known history of cataracts or retinal detachment
Patients with gastric bypass or any condition that would be expected to affect drug absorption
Patients with history of meeting DSM-5 criteria for alcohol or substance abuse or dependence within the 6 months before enrolment
Prior participation in any clinical trials involving experimental or investigational drugs within 6 months before enrolment or during the study
Pregnant breastfeeding or planning to become pregnant or breastfeed during the study
Employee or immediate relative of an employee of the Sponsor any of its affiliates or partners or the study center
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Proportion of participants with treatment-emergent adverse events (TEAEs) [Time frame: Throughout the study period]
Time frame: Throughout the study period
Secondary Outcome
Outcome
TimePoints
1. Change in PANSS total score from baseline
2. Change in PANSS positive subscale score from baseline
3. Change in PANSS negative subscale score from baseline
4. Change in CGI-S score from baseline
1. Days 7, 14, 21, 28, 35 & 42
2. Days 7, 14, 21, 28, 35 & 42
3. Days 7, 14, 21, 28, 35 & 42
4. Days 7, 14, 21, 28, 35 & 42
1.Change in YMRS total score from baseline (Time frame: Days 7, 14 & 21)
2. Change in Clinical Global Impression - Bipolar Version (CGI-BP) score from baseline (Time frame: Days 7, 14 & 21)
3. Change in MADRS total score from baseline (Time frame: Days 7, 14 & 21)
1. (Time frame: Days 7, 14 & 21)
2. (Time frame: Days 7, 14 & 21)
3. (Time frame: Days 7, 14 & 21)
Target Sample Size
Total Sample Size="172" Sample Size from India="172" Final Enrollment numbers achieved (Total)= "172" Final Enrollment numbers achieved (India)="172"
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 prospective, multicentre, single-arm, Phase IV, open-label study. The study will be conducted at approximately 15 to 20 centres in 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 and will be undergoing various assessments as mentioned in Schedule of Assessment (Appendix I). Screening number will be allotted to every screened patient. At screening visit, the Investigator or his/her designee will provide prospective patient 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, study-specific screening [including inclusion and exclusion criteria, medical and medication history, demography, vitals, physical and laboratory examination, 12-Lead Electrocardiogram (ECG), PANSS score, YMRS score, CGI-S score, CGI-BP score and MADRS score] will be performed. Evaluation of concomitant medications and adverse/ serious adverse events will be done.
After confirming the eligibility, patients will be enrolled by allotting the enrollment number. The enrolled patients will be given study drugs Cariprazine Capsules 1.5 mg/3 mg/4.5 mg/ 6 mg once daily as mentioned in the section 10.1 Treatments Administered for the Investigational product dosage. Treatment duration will be 6 weeks for schizophrenia patient, and 3 weeks for Bipolar I disorder patient.
Efficacy endpoints assessment for a particular patient will be done by the same assessor (psychiatrist) for all the study visits.
Patients will be provided with diary to record details about study drug administration and adverse events. Patients will be required to bring completed diary of previous visit at upcoming visit to facility.