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CTRI Number  CTRI/2015/05/005820 [Registered on: 26/05/2015] Trial Registered Prospectively
Last Modified On: 27/04/2016
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Randomized, Crossover Trial 
Public Title of Study   Bioequivalence study of Quetiapine Fumarate prolonged-release tablets EQ 400 mg base in patients suffering from schizophrenia 
Scientific Title of Study   A randomized, open-label, two-treatment, two-period, cross-over, multiple dose, steady state, multi-centre comparative bioequivalence study of Quetiapine Fumarate prolonged-release tablets EQ 400 mg base manufactured by Amneal Life Sciences Pvt. Ltd. India with SEROQUEL XL (Quetiapine Fumarate) 400 mg prolonged-release tablets marketed by AstraZeneca UK Ltd. in patients suffering from schizophrenia under fasting conditions. 
Trial Acronym  Not Applicable 
Secondary IDs if Any  
Secondary ID  Identifier 
ARL/CT/14/005, version 00 amendment dated 13 May 2015  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ashoka Singh 
Designation  General Manager- Clinical Operations 
Affiliation  Veeda Clinical Research Pvt. Ltd. 
Address  Veeda Clinical Research Pvt. Ltd. Shivalik Plaza-A, Near IIM, Ambawadi, Ahmedabad-380015, Gujarat India Ahmadabad GUJARAT 380015 India Ahmadabad GUJARAT 380015 India

Ahmadabad
GUJARAT
380015
India 
Phone  079-30013000  
Fax    
Email  ashoka.singh@veedacr.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Ashoka Singh 
Designation  General Manager- Clinical Operations 
Affiliation  Veeda Clinical Research Pvt. Ltd. 
Address  Veeda Clinical Research Pvt. Ltd. Shivalik Plaza-A, Near IIM, Ambawadi, Ahmedabad-380015, Gujarat India Ahmadabad GUJARAT 380015 India Ahmadabad GUJARAT 380015 India

Ahmadabad
GUJARAT
380015
India 
Phone  079-30013000  
Fax    
Email  ashoka.singh@veedacr.com  
 
Details of Contact Person
Public Query
 
Name  Dr Ashoka Singh 
Designation  General Manager- Clinical Operations 
Affiliation  Veeda Clinical Research Pvt. Ltd. 
Address  Veeda Clinical Research Pvt. Ltd. Shivalik Plaza-A, Near IIM, Ambawadi, Ahmedabad-380015, Gujarat India Ahmadabad GUJARAT 380015 India Ahmadabad GUJARAT 380015 India

Ahmadabad
GUJARAT
380015
India 
Phone  079-30013000  
Fax    
Email  ashoka.singh@veedacr.com  
 
Source of Monetary or Material Support  
Amneal Pharmaceuticals Company GmbH, Turmstrasse 30, 6312 Steinhausen, Switzerland. 
 
Primary Sponsor  
Name  Amneal Pharmaceuticals Company GmbH 
Address  Amneal Pharmaceuticals Company GmbH, Turmstrasse 30, 6312 Steinhausen, Switzerland. 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
Veeda Clinical Research Pvt Ltd  Veeda Clinical Research Pvt. Ltd. Shivalik Plaza, Near I.I.M., Ambawadi, Ahmedabad – 380 015, 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 Bakul Buch  Hatkesh Healthcare Foundation  Department of Psychiatry, Hatkesh Healthcare Foundation, Saraswati Mandir Complex, Opposite Bhutnath Temple, College Road, Junagadh -362001, Gujarat
Junagadh
GUJARAT 
9824017400

bakulbuch@gmail.com 
Dr Rajendra Anand  Kanoria Hospital & Research Centre  Psychiatry OPD, Kanoria Hospital & Research Centre, Hansol Gandhinagar Highway, Indira Bridge Corner, Bhat Gam, Ahmedabad - 382428, Gujarat"
Ahmadabad
GUJARAT 
9825220330

drrajendraanand@yahoo.com 
Dr Ashok Kumar Goyal  Malpani Multispeciality Hospital  Department of Psychiatry, Malpani Multispeciality Hospital SP-6, Vishwakarma Institutional Area, Road-1, Sikar Road, Jaipur- 302013, Rajasthan"
Jaipur
RAJASTHAN 
9413343445

goyalashokdr@gmail.com 
Dr Nehal Shah  Sanjivani Superspeciality Hospital  Psychiatry OPD, Sanjivani Superspeciality Hospital, 1, Uday Park Society, Near Sunrise Park, Vastrapur, Ahmedabad - 380015, Gujarat
Ahmadabad
GUJARAT 
9925049569

doctornehal@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 4  
Name of Committee  Approval Status 
Hatkesh Healthcare Foundation Ethics Committee  Approved 
Institutional Ethics Committee - Malpani Multispeciality Hospital  Approved 
Kanoria Ethics Committee  Approved 
Sanjivani Hospital Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  schizophrenia,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Quetiapine Fumarate prolonged-release tablets EQ 400 mg base  Patients will be housed for entire study period from study days 0 to 11 and will be administered IP under supervision of investigator/ designee on all 10 study days e.g. period I – days 1 to 5 & period II – days 6 to 10. In morning of each study day, after overnight fast of at least 10 hours, patient will be administered oral dose of single tablet of IP (Quetiapine Fumarate prolonged-release tablets EQ 400 mg base as per site specific randomization schedule) with approximately 240 mL of water at ambient temperature in sitting position, under supervision of investigator/ designee. Followed by supervised IP administration, mouth check will be done by investigator/ designee to check compliance to dosing. Mouth check will include a thorough check of the oral cavity using torch (flash light) to confirm that patient has swallowed the IP tablet properly. 
Comparator Agent  SEROQUEL XL (Quetiapine Fumarate) 400 mg prolonged-release tablets  Patients will be housed for entire study period from study days 0 to 11 and will be administered IP under supervision of investigator/ designee on all 10 study days e.g. period I – days 1 to 5 & period II – days 6 to 10. In morning of each study day, after overnight fast of at least 10 hours, patient will be administered oral dose of single tablet of IP (Quetiapine Fumarate prolonged-release tablets EQ 400 mg base as per site specific randomization schedule) with approximately 240 mL of water at ambient temperature in sitting position, under supervision of investigator/ designee. Followed by supervised IP administration, mouth check will be done by investigator/ designee to check compliance to dosing. Mouth check will include a thorough check of the oral cavity using torch (flash light) to confirm that patient has swallowed the IP tablet properly. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1. Either sex, aged 18 to 65 years (both inclusive) having clinical diagnosis of schizophrenia (DSM IV-TR)
2. Receiving Quetiapine Fumarate prolonged-release tablets treatment for at least 1 month prior to randomization and is on Quetiapine Fumarate prolonged-release tablets EQ 400 mg base once daily dosage at the time of screening.
3. 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.
4. Females of childbearing potential (who has not completed 1 year after menopause & have not gone through hysterectomy or bilateral tubal ligation) must have a negative pregnancy test (at screening, before randomization and before check-in to housing e.g. day 0) as well as must be non-lactating at screening and must agree to use an effective contraceptive method during study. 
 
ExclusionCriteria 
Details  1. History of allergic reactions to Quetiapine or other component of the prolonged-release formulation.
2. Concurrent primary psychiatric or neurological diagnosis, including organic mental disorder, alcoholic and other toxic psychoses, severe tardive dyskinesia, or idiopathic Parkinson’s disease.
3. History of suicidal tendencies (e.g. suicidal attempts) within the past 3 months prior to screening or immediate risk of harm to self or other at the time of screening, as judged by the investigator.
4. History of Neuroleptic Malignant Syndrome, cardiovascular disease [ischemic heart disease (including myocardial infarction), heart failure (including congestive heart failure or significant heart hypertrophy) or conduction abnormalities (including bradyarrythmia, congenital QT prolongation or family history of QT prolongation)], cerebrovascular disease, drug induced leucopenia/ neutropenia, seizures or with conditions that potentially lower the seizure threshold e.g. Alzheimer’s dementia
5. History of multiple syncopal episodes or presence of significant orthostatic hypotension at screening or before check-in to housing on day 0; Orthostatic hypotension will be considered when there is drop in systolic blood pressure of 30 mm Hg or more or diastolic blood pressure of 20 mm Hg or more on standing from supine measurements.
6. Current/ recent (within 3 months) history of uncontrolled epilepsy or risk for seizures
7. A medical or surgical condition that might interfere with the absorption, metabolism or excretion of Quetiapine
8. Drug abuse or alcohol dependence in last 1 year period before enrolment (except dependence in full remission), as defined by DSM IV-TR criteria and as positive result in breath alcohol testing/ urine screen for drug of abuse (except for prescribed benzodiazepines).
9. Any of the following investigational abnormality in screening:
ï‚· WBC count 3000/mm3 (3.0x109/l),
ï‚· Absolute Neutrophil Count 1500/mm3 (1.5x109/l),
ï‚· Serum creatinine 1.5 mg/dL
ï‚· QTc 500 milliseconds (in ECG of screening or day 0)
ï‚· SGOT/ SGPT 3 times Upper Limit of Normal range (ULN)
ï‚· HbA1c 9%
ï‚· Reactive to antiHIV, HBsAg, antiHCV
10. Use of any contraindicated medications in the 14 days preceding enrolment
Use of any of the following in the 14 days preceding enrolment 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Other 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To assess bioequivalence of the test product (T) – Quetiapine Fumarate prolonged-release tablets EQ 400 mg basemanufactured by Amneal Life Sciences Pvt. Ltd., India compared to that of the reference product (R)– SEROQUEL XL(Quetiapine Fumarate) 400 mg prolonged-release tablets marketed by AstraZeneca UK Ltd. in patients suffering from schizophrenia who are already on a stable regimen with Quetiapine Fumarate prolonged-release tablets EQ 400 mg base once daily  01.00, 02.00, 03.00, 04.00, 04.50, 05.00, 05.50, 06.00, 06.50, 07.00, 07.50, 08.00, 09.00, 10.00, 11.00, 12.00, 14.00, 18.00 and 24.00 hrs 
 
Secondary Outcome  
Outcome  TimePoints 
To monitor the adverse events, safety and tolerability of a multiple doses of Quetiapine Fumarate prolonged-release tablets EQ 400 mg base in patients suffering from schizophrenia who are already on a stable regimen with Quetiapine Fumarate prolonged-release tablets EQ 400 mg base once daily.  Not Applicable 
 
Target Sample Size   Total Sample Size="64"
Sample Size from India="64" 
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" 
Phase of Trial   N/A 
Date of First Enrollment (India)   28/05/2015 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="0"
Months="9"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   Not Applicable 
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary   This is A randomized, open-label, two-treatment, two-period, cross-over, multiple dose, steady state, multi-centre comparative bioequivalence study of Quetiapine Fumarate prolonged-release tablets EQ 400 mg base manufactured by Amneal Life Sciences Pvt. Ltd. India with SEROQUEL XL (Quetiapine Fumarate) 400 mg prolonged-release tablets marketed by AstraZeneca UK Ltd. in patients suffering from schizophrenia under fasting conditions.A randomized, open-label, two-treatment, two-period, cross-over, multiple dose, steady state, multi-centre comparative bioequivalence study of Quetiapine Fumarate prolonged-release tablets EQ 400 mg base manufactured by Amneal Life Sciences Pvt. Ltd. India with SEROQUEL XL (Quetiapine Fumarate) 400 mg prolonged-release tablets marketed by AstraZeneca UK Ltd. in patients suffering from schizophrenia under fasting conditions.Primary objective: To characterize pharmacokinetic profile of the test product (T) – Quetiapine Fumarate prolonged-release tablets EQ 400 mg basemanufactured by Amneal Life Sciences Pvt. Ltd., India compared to that of the reference product (R)– SEROQUEL XL(Quetiapine Fumarate) 400 mg prolonged-release tablets marketed by AstraZeneca UK Ltd. in patients suffering from schizophrenia who are already on a stable regimen with Quetiapine Fumarate prolonged-release tablets EQ 400 mg base once daily and to assess their bioequivalence.
Secondary Objective: To monitor the safety and tolerability of a multiple doses of Quetiapine Fumarate prolonged-release tablets EQ 400 mg base in patients suffering from schizophrenia who are already on a stable regimen with Quetiapine Fumarate prolonged-release tablets EQ 400 mg base once daily.Patients will be housed for entire study period from study days 0 to 11 and will be administered IP under supervision of investigator/ designee on all 10 study days e.g. period I – days 1 to 5 & period II – days 6 to 10.
In morning of each study day, after overnight fast of at least 10 hours, patient will be administered oral dose of single tablet of IP (Quetiapine Fumarate prolonged-release tablets EQ 400 mg base as per site specific randomization schedule) with approximately 240 mL of water at ambient temperature in sitting position, under supervision of investigator/ designee. On study days 5 & 10, post dose sampling will be done at 01.00, 02.00, 03.00, 04.00, 04.50, 05.00, 05.50, 06.00, 06.50, 07.00, 07.50, 08.00, 09.00, 10.00, 11.00, 12.00, 14.00and 18.00 hours after IP dose.
On study days 6 & 11, last post dose sample will be collected at 24.00 hours after IP dose on days 5 & 10, respectively.
Total number of pharmacokinetic blood samples: 44 (22/ period).
Total blood loss in study: approximately 321 ml for patient (including 3 safety samples: approx 15 ml at screening and approx 10 ml at end of each period). On study days 5 & 10, post dose sampling will be done at 01.00, 02.00, 03.00, 04.00, 04.50, 05.00, 05.50, 06.00, 06.50, 07.00, 07.50, 08.00, 09.00, 10.00, 11.00, 12.00, 14.00and 18.00 hours after IP dose.
On study days 6 & 11, last post dose sample will be collected at 24.00 hours after IP dose on days 5 & 10, respectively.
Total number of pharmacokinetic blood samples: 44 (22/ period).
Total blood loss in study: approximately 321 ml for patient (including 3 safety samples: approx 15 ml at screening and approx 10 ml at end of each period) 
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