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
|
|
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. |