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CTRI Number  CTRI/2018/09/015741 [Registered on: 18/09/2018] Trial Registered Prospectively
Last Modified On: 19/11/2019
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Randomized, Crossover Trial 
Public Title of Study   Study of Cariprazine Capsules 6 mg in Schizophrenia or Bipolar disorder I patients. 
Scientific Title of Study   An, Open-label, Randomized, Three-Treatment, Four-sequence, Two-period, Cross-over, Multiple dose, Steady state Clinical Bioequivalence Study of two different formulations of Cariprazine Capsules 6 mg of Aurobindo Pharma Limited, India (T1 and T2) with VRAYLAR (Cariprazine) Capsules 6mg of Allergan USA, Inc. Irvine, CA 92612, USA(Reference) in patients already receiving a stable dose of Cariprazine capsules 6 mg 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
CR192-18, Version 1.0, Amendment-01 Dated 01.09.2018  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Subhra Lahiri 
Designation  Associate Vice President 
Affiliation  AXIS Clinicals Ltd 
Address  Axis Clinicals Limited, 1-121/1, Miyapur, Hyderabad

Hyderabad
ANDHRA PRADESH
500049
India 
Phone  04040408064  
Fax  04040408060  
Email  Subhra.L@axisclinicals.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Subhra Lahiri 
Designation  Associate Vice President 
Affiliation  AXIS Clinicals Ltd 
Address  Axis Clinicals Limited, 1-121/1, Miyapur, Hyderabad

Hyderabad
ANDHRA PRADESH
500049
India 
Phone  04040408064  
Fax  04040408060  
Email  Subhra.L@axisclinicals.com  
 
Details of Contact Person
Public Query
 
Name  Dr Subhra Lahiri 
Designation  Associate Vice President 
Affiliation  AXIS Clinicals Ltd 
Address  Axis Clinicals Limited, 1-121/1, Miyapur, Hyderabad

Hyderabad
ANDHRA PRADESH
500049
India 
Phone  04040408064  
Fax  04040408060  
Email  Subhra.L@axisclinicals.com  
 
Source of Monetary or Material Support  
APL Research Center Aurobindo Pharma Limited Survey No -313, Bachupally Village, Qutubullapur Mandal, Hyderabad  
 
Primary Sponsor  
Name  APL Research Center 
Address  Aurobindo Pharma Limited Survey No -313, Bachupally Village, Qutubullapur Mandal, Hyderabad -500 090, India  
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
Axis Clinicals Limited  1-121/1, Miyapur, Hyderabad-500049 Andhra Pradesh, INDIA  
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Timir Kumar Chandrakant Shah  Divyam Hospital  Block No.84, Palsana Cross Road, National Highway No.8, Palsana, Surat, Gujarat, 394315
Surat
GUJARAT 
9825137443

drtcshah@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee, Divyam Hospital  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  (1) ICD-10 Condition: F208||Other schizophrenia,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Cariprazine Capsules 6 mg (Test 2)  Manufactured by:Aurobindo Pharma Limited, India 
Intervention  Cariprazine Capsules 6mg (Test 1)  Manufactured by: Aurobindo Pharma Limited, India 
Comparator Agent  VRAYLAR (cariprazine) Capsules 6mg   Distributed by: Allergan USA, Inc. Irvine, CA 92612, USA 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1.Male and female patient aged 18 to 65 Years (both inclusive) with body mass index between 18.5 to 30 kg/m2 (both inclusive)
2.Patient already receiving stable dose of Cariprazine 6 mg once daily for at least 04 weeks before screening only
3.Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar I disorder without psychotic features
OR
Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for Schizophrenia
4.Patient having adequate hematologic reserve at screening as per principal investigator assessment
5.Patient having adequate and stable hepatic and renal function as per principal investigator assessment at screening only
6.Patient should have no clinically significant abnormality in any of the laboratory parameters including ECG and Chest X-ray as per the discretion of Principal Investigator at screening only
7.Patient and Legally Acceptable Representative had given consent after being advised of the nature and risks of the study
8.Female patient of childbearing potential must have a negative serum pregnancy test
9.Females must use acceptable and effective methods of contraception such as the following:
9.1 Tubal sterilization (tubal ligation performed more than one month before Study Day 1; transcervical tubal occlusion procedure performed more than six months before Study Day 1)
9.2 Intrauterine Device (IUD)
9.3 Progestin Implant (i.e. Implanon or its equivalent)
9.4 Progestin injection or progestin oral contraceptive pill + one barrier method (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide + a male or female condom)
9.5 Two barrier methods used together (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide + a male or female condom)
9.6 Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner) during the study and till 60 days post dose
10.Patient having normal physical examination, clinical laboratory test results, and electrocardiogram (ECG) results or abnormal findings that are judged not clinically significant by the Principal Investigator (PI) at screening only
11.Patient having laboratory values as follows:
11.1 Absolute neutrophil count (ANC) greater than or equal to 1500/μL
11.2 Hemoglobin (Hb) greater than or equal to 9 g/dL.
11.3 Platelets greater than or equal to 100,000/ μL
11.4 AST or ALT must be less than 3 x ULN
11.5 Total bilirubin less than 1.5 x the institutional ULN¬¬
11.6 Creatinine less than or equal to 1.5 x ULN
 
 
ExclusionCriteria 
Details  1.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
2.Active suicidal or homicidal intent (as documented by informants or in the Investigator’s opinion) or a prior suicide or homicide attempt in the past 2 years
3.At imminent risk of injuring self or others or causing significant damage to property, as judged by the Investigator
4.Documented disease of the central nervous system that could interfere with the study assessments, including but not limited to stroke, tumor, Parkinson’s disease, organic brain disease, seizure disorder (except for febrile convulsions during infancy), chronic infection, or neurosyphilis; or patients who had suffered a traumatic brain injury resulting in significant impairment
5.Patient with history of clinically significant cardiovascular, renal, hepatic, respiratory, endocrine (except noninsulin-dependent diabetes mellitus), or gastrointestinal disease
6.Patient with known history of significant orthostatic hypotension (i.e., a drop in systolic blood pressure of 20 mm hg or more and / or a drop in diastolic blood pressure of 10 mm Hg or more on standing)
7.Patient with cataracts
8.Current or past history of tardive dyskinesia or neuroleptic malignant syndrome
9.Patient found to be positive for HIV and/or HBsAg and/or HCV at preliminary screening
10.Patient with history of epilepsy or seizures or are comatose or experiencing severe central nervous system depression
11.Patient is unable to communicate with the investigator
12.Patients with history of allergic reactions to Cariprazine or chemically related psychotropic drugs
13.Patient is smoker or alcoholic
14.Patient had history of difficulty with donating blood or difficulty in accessibility of veins
15.Patient consumed grape fruit/mosumbi/sweet lime juice within the 48 hours prior to study check-in
16.Female patient who is pregnant or currently breast-feeding
17.Females of child bearing potential unwilling to use acceptable contraception throughout the trial and for 14 days after the last dose of study drug
18.Patient participation in another clinical trial within the preceding 90 days of study starts
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
AUC0-τ: Area under the blood concentration – time curve over the steady state dosing interval.
Cmax-ss: Maximum concentration over the steady state dosing interval 
Venous blood samples 4 mL will be withdrawn within 5 minutes prior to dosing on Day 1, 2, 3 and 4 Period I and 6, 7 and 8 Period II to confirm steady state condition
Venous blood samples 4 mL will be withdrawn on Day 4 and 8 at 0.50, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 4.50, 5.00, 5.50, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post drug administration.
The blood will be collected in a pre-labeled vacutainer tubes containing K2EDTA
 
 
Secondary Outcome  
Outcome  TimePoints 
Cmin-ss: Minimum concentration over the steady state dosing interval.
Cavg-ss: Average concentration over the steady state dosing interval.
Percentage fluctuation: [Cmax-ss – Cmin-ss/ Cavg-ss] X 100
Tmax-ss: Time of maximum measured blood concentration over the steady state dosing interval.
Cpd (pre-dose concentration)-Pre-dose concentrations determined before a dose at steady state.
Swing: [Cmax-ss-Cmin-ss/ Cmin-ss]
Safety and tolerability
 
Venous blood samples 4 mL will be withdrawn within 5 minutes prior to dosing on Day 1, 2, 3 and 4 Period I and 6, 7 and 8 Period II to confirm steady state condition
Venous blood samples 4 mL will be withdrawn on Day 4 and 8 at 0.50, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 4.50, 5.00, 5.50, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post drug administration.
The blood will be collected in a pre-labeled vacutainer tubes containing K2EDTA
 
 
Target Sample Size   Total Sample Size="20"
Sample Size from India="20" 
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="20" 
Phase of Trial   Phase 1 
Date of First Enrollment (India)
Modification(s)  
19/10/2018 
Date of Study Completion (India) 29/10/2018 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="0"
Months="2"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   None 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

This is an open-label, randomized, three-treatment, four-sequence, two-period, cross-over, multiple dose, steady state, clinical bioequivalence study of two different formulations of Cariprazine Capsules 6 mg of Aurobindo Pharma Limited, India (T1 and T2) with VRAYLAR (Cariprazine) Capsules 6mg of Allergan USA, Inc. Irvine, CA 92612, USA (Reference) in patients already receiving a stable dose of Cariprazine capsules 6 mg.

Patients will be titrated upwards with VRAYLAR (Cariprazine) capsules 1.5 mg on day -38, 3 mg on day -37, 4.5 mg on day -36, and 6 mg on day -35 onwards clinically stabilized for at least 04 weeks. Patients with bipolar disorder I will be given Lithium carbonate 600 to 900 mg tablets once or twice daily as per the Investigator discretion. Patients will be given Alprazolam or Nitrazepam or Lorazepam as and when required as per the Investigator discretion for Schizophrenia or Bipolar disorder I patients.

The study will be planned to investigate bioequivalence of Aurobindo Pharma’s two Test formulations with Reference formulation (T1 Vs R and T2 Vs R) so, the study will be divided into two groups each with 10 patients to compare bioequivalence of T1 with R and other T2 with R.

 
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