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CTRI Number  CTRI/2019/02/017809 [Registered on: 25/02/2019] Trial Registered Prospectively
Last Modified On: 10/12/2021
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study   NA 
Study Design  Randomized, Crossover Trial 
Public Title of Study   A bioequivalence study of Asenapine Maleate EQ 10 mg base sublingual spray with SAPHRIS® (Asenapine) sublingual tablets EQ 10 mg in adult patients with schizophrenia or bipolar I disorder 
Scientific Title of Study   A multicenter open label randomized balanced two treatment two period two sequence crossover multiple dose bioequivalence study of Asenapine Maleate EQ 10 mg base sublingual spray of Navinta LLC USA with SAPHRIS® (Asenapine) sublingual tablets EQ 10 mg base Distributed by Allergan USA Inc. Irvine CA 92612 in adult patients with schizophrenia or bipolar I disorder under fasting conditions 
Trial Acronym  18 VIN 0437 
Secondary IDs if Any  
Secondary ID  Identifier 
18 VIN 0437 version 01 08 Aug 2018  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ashoka Kumar Singh  
Designation  Head Clinical Operations 
Affiliation  Veeda Clinical research Pvt Ltd 
Address  Shivalik Plaza A Near IIM Ambawadi
NA
Ahmadabad
GUJARAT
380 015
India 
Phone  079-30013000  
Fax  079-30013010  
Email  ashoka.singh@veedacr.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Yogesh Patel  
Designation  Medical Monitor- Snr. Manager 
Affiliation  Veeda Clinical research Pvt Ltd 
Address  Shivalik Plaza A Near IIM Ambawadi

Ahmadabad
GUJARAT
380 015
India 
Phone  079-30013000  
Fax  079-30013010  
Email  Yogesh.AP@veedacr.com  
 
Details of Contact Person
Public Query  
Name  Dr Ashoka Kumar Singh  
Designation  Head Clinical Operations 
Affiliation  Veeda Clinical research Pvt Ltd 
Address  Shivalik Plaza A Near IIM Ambawadi

Ahmadabad
GUJARAT
380 015
India 
Phone  079-30013000  
Fax  079-30013010  
Email  ashoka.singh@veedacr.com  
 
Source of Monetary or Material Support  
Navinta LLC USA 
 
Primary Sponsor  
Name  Navinta LLC 
Address  1499 Lower Ferry Road Ewing NJ 08618 USA Tel no.: 6098831135 Fax no.: 6098831137 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
Veeda Clinical Research Pvt Ltd  Shivalik Plaza Nr IIM Ambawadi Ahmedabad 380015 Gujarat India 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 4  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Ashish Contractor  Body Line Hospital  Clinical Research Department Basement,Opp.Annpurna Hall,Near Dev Status,New Vikas Gruh Road,paldi,Ahmedabad 7 Gujrat India
Ahmadabad
GUJARAT 		 9824012867

cdrashish@gmail.com 
Dr Rajendra Anand  Kanoria Hospital And Research Centre  Kanoria Hospital And Research Centre Ground Floor Airport Gandhinagar Highway Village Bhat Dist.Gandhinagar Gujarat 382428
Gandhinagar
GUJARAT 		 9824017400

drrajendraanand@yahoo.com 
Dr Poorav Patel  Medistar Multispeciality Hospital   Department of psychiatry, Second Floor Trimurti Avenue ,Medistar Cross Road ,NH 8,Himatnagar 383001,Gujarat India
Sabar Kantha
GUJARAT 		 9428772609

drpooravpatel@gmail.com 
Dr Ramashanker Yadav  Saviour Multispeciality Hospital  Department of psychiatry, Third Floor, Nr.Bharat Petrol Pump,Nr.lakhudi Talav,Stadium Road,Navrangpura,Ahmedabad 380014 Gujarat
Ahmadabad
GUJARAT 		 8264049261

yadavramashankar@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 4  
Name of Committee  Approval Status 
Bodyline Hospital Institutional Ethics   Approved 
Kanoria Ethics Committee  Approved 
Medistar Hospital Ethics Committee  Approved 
Saviour Hospital Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
No Objection Certificate 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: F319||Bipolar disorder, unspecified, (2) ICD-10 Condition: F209||Schizophrenia, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Asenapine Maleate EQ 10 mg base sublingual spray of Navinta LLC USA  In period-I (from day 1 to day 7) patients will receive either the Test product or the reference product every 12 hours for 7 days. In period-II (from day 8 to day 14) patients will be switched to another product for a second period of 7 days 
Comparator Agent  SAPHRIS® (Asenapine) sublingual tablets EQ 10 mg base Distributed by Allergan USA Inc Irvine CA 92612  In period-I (from day 1 to day 7) patients will receive either the Test product or the reference product every 12 hours for 7 days. In period-II (from day 8 to day 14) patients will be switched to another product for a second period of 7 days. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1. Men and non-pregnant women (both
inclusive) having clinical diagnosis of Schizophrenia or Bipolar I disorder.
2. Patients should be appropriate candidates for asenapine maleate sublingual tablet or spray EQ 10 mg base twice daily therapy and have been receiving a stable dose of asenapine maleate sublingual tablet EQ 10 mg base twice daily therapy for at least
three months prior to screening.
3. Adequate hematological parameters hepatic and renal function at screening defined by:
Total white blood cell count more than 4000/cmm
ANC more than equal to 2000/mm3
Platelet count more than equal to 75000/mm3
Haemoglobin more than equal to 9.0 gm/dL
Bilirubin less than and equal to 1.5 X ULN (upper limit of normal)
AST/ALT less than an equal to 3 X ULN
S. creatinine less than an equal to 1.5 X ULN or creatinine clearance more than an equal to 60 ml/min
4. Patients should be otherwise healthy as determined by physical examination medical history and routine hematologic and biochemical tests.
5. Willing and able to comply with housing restrictions and other protocol requirements as indicated by signed written informed consent witnessed by a legally acceptable representative.
6. Sexually active women unless surgically sterile (at least 6 months prior to study drug administration) or amenorrhoea for at least 12 consecutive months must agree to use an effective method of avoiding pregnancy (including oral transdermal or implanted contraceptives [any hormonal method in conjunction with a secondary method] intrauterine device female condom with spermicide diaphragm with spermicide absolute sexual abstinence use of condom with spermicide by sexual partner) from screening during the study and till the study completion (i.e. post study safety assessment after last PK sample collection in period II).
And
Sexually active women must have a negative pregnancy test (at screening before check-in on day 0) as well as must be non lactating at the time of screening.
7. No participation in any clinical study within the past 60 days. 
 
ExclusionCriteria 
Details  1. A history of allergic or adverse reactions to asenapine maleate or any comparable or similar product.
2. A history of severe hepatic impairment, drug induced leukopenia/neutropenia.
3. Concurrent (other than Schizophrenia or Bipolar I disorder) primary psychiatric or neurological diagnosis, including organic
mental disorder, severe tardive dyskinesia, or idiopathic Parkinson’s disease, cognitive and motor impairment.
4. A history of granulocytopenia or myelo proliferative disorders (drug-induced or idiopathic).
5. Patient with the history or presence of significant orthostatic hypotension (i.e. a drop in systolic blood pressure of 30 mm Hg or more and/or a drop in diastolic blood pressure of 20 mm Hg or more on standing) at the time of screening.
6. Concurrent use of antihypertensive medication or any medication that might predispose to orthostatic hypotension.
7. A medical or surgical condition that might interfere with the absorption, metabolism, or excretion of asenapine maleate.
8. A history of epilepsy or risk for seizures.
9. Concurrent use of other drugs known to suppress bone marrow function.
10. Expected changes in concomitant medications during the period of study.
11. Positive tests for drug or alcohol abuse at screening or baseline.
12. A history of alcohol or drug dependence by Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) or later criteria during the 6-month period immediately prior to study entry.
13. Compliance with outpatient medication schedule not expected.
14. History of multiple syncopal episodes or stroke.
15. Patients with dementia related psychosis.
16. Patients with a history of Neuroleptic Malignant Syndrome (NMS).
17. Presence of uncontrolled metabolic disorders including uncontrolled diabetes mellitus (Fasting blood glucose levels more than an equal to 160 mg/dl and HbA1c more than an equal to 8 %), Serum total cholesterol more than an equal to 300 mg/dl and fasting serum triglyceride levels more than an equal to 300 mg/dl.
18. Patients with the following cardiac conditions: Recent myocardial infarction (less than 12 months)
Persistent (3 consecutive electrocardiograms [ECGs] performed 2 to 5 minutes apart) prolongation of the QTc(Fridericia) interval to more than 480 msec;
History of cardiac arrhythmias or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including: bradycardia, cardiac arrhythmias, hypokalemia or hypomagnesemia, concomitant use of other drugs that prolong the QTc interval; and presence of congenital prolongation of the QT interval (QTc more than 450 ms)
19. Patients with clinically significant hyperprolactinemia or with possible prolactin dependent tumor.
20. Use of any of the following medications within 14 days or at least five half-lives have not been passed between last dose of the previous medication and first dose of the study medication, preceding enrollment including but not limited to:
Strong CYP1A2 Inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin etc.).
CYP2D6 Substrates and Inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline etc).
Drugs known to prolong QTc including Class 1A
antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), antipsychotic 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Pharmacy-controlled Randomization 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To demonstrate the bioequivalence at steady
state of Asenapine Maleate EQ 10 mg base sublingual spray of Navinta LLC, USA with SAPHRIS® (Asenapine) sublingual tab EQ 10 mg base Distributed by Allergan USA Inc. Irvine CA 92612 in adult patients with schizophrenia or bipolar I disorder under fasting conditions.
To monitor the safety and tolerability profile of the study formulations. 		 A total of 36 blood samples each of 07 mL will be collected during the study for PK analysis. The predose blood sample will be
scheduled to be collected within 5 minutes before morning dosing on days 5 6 7 in period I and days 12 13 14 in period II of the study.
On day 7 & day 14, the post-dose blood samples will be drawn at
0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00,
8.00, 10.00, 12.00 hour following morning drug administration 
 
Secondary Outcome  
Outcome  TimePoints 
To monitor the safety and tolerability profile of the study formulations  Blood pressure pulse rate and body temperature shall be
monitored and immediate medical care shall be provided for any significant abnormalities. Orthostatic hypotension will be assessed at screening within 40 min after 06 hr of dosing on day1 day7 day8 and day14. Physical and other parameters will be checked on at Screening before dosing on day1 day8 and during post study safety assessment after last PK sample in periodII 
 
Target Sample Size   Total Sample Size="24"
Sample Size from India="24" 
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="40" 
Phase of Trial   N/A 
Date of First Enrollment (India)   05/03/2019 
Date of Study Completion (India) 31/12/2018 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="0"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   Nil 
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary   Patient who have been taking a stable dose of sublingual tablet, EQ 10 mg base twice daily therapy for at least three months will be eligible for the study participation. Patients who are eligible to participate in the study based on screening assessments would receive their own established dose twice daily (at least 12 hours apart) for 14 days in a crossover design. There will be no wash-out period between two study periods. 
In period-I (from day 1 to day 7), patients will receive either the Test product or the reference product every 12 hours for 7 days. 
In period-II (from day 8 to day 14), patients will be switched to another product for a second period of 7 days. After the study is completed (after last PK sample collection on day 14), patients could be continued on twice daily dose of asenapine maleate EQ 10 mg base using an approved asenapine maleate product as prescribed by their clinicians. The evening dose of asenapine on day 7 & day 14 will be administered after last PK sample collection of 12 hours. Blood samples for PK assessment will be collected at various time points in both the periods and plasma concentration of asenapine will be quantified using validated analytical method.
 
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