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CTRI Number  CTRI/2017/08/009520 [Registered on: 28/08/2017] Trial Registered Retrospectively
Last Modified On: 11/09/2020
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Randomized, Crossover Trial 
Public Title of Study   Bioequivalence Study of Ivabradine 15 mg prolonged release tablet in healthy human male subjects 
Scientific Title of Study   A pilot, open-label, balanced, randomized, fourperiod, two-sequence, two-treatment cross-over study to study the relative bioavailability of test Ivabradine prolonged release tablets (15 mg) given once a day versus Coralan® film-coated tablets (7.5 mg) twice a day at 12 hours apart under fasting and fed conditions in healthy human male subjects 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
Protocol Version 2, dated 06 June 2016  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Adarsh Kumar Garg 
Designation  Principal Investigator 
Affiliation  Lambda Therapeutic Research Ltd 
Address  Clinical Department, Lambda Therapeutic Research Ltd., Lambda house, Plot no.38, Survey no. 388, Near Silver Oak Club, S. G. Highway, Gota, Ahmedabad 382481,Gujarat, India

Ahmadabad
GUJARAT
382481
India 
Phone  07940202020  
Fax  07940202021  
Email  adarshgarg@lambda-cro.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Adarsh Kumar Garg 
Designation  Principal Investigator 
Affiliation  Lambda Therapeutic Research Ltd 
Address  Clinical Department, Lambda Therapeutic Research Ltd., Lambda house, Plot no.38, Survey no. 388, Near Silver Oak Club, S. G. Highway, Gota, Ahmedabad 382481,Gujarat, India


GUJARAT
382481
India 
Phone  07940202020  
Fax  07940202021  
Email  adarshgarg@lambda-cro.com  
 
Details of Contact Person
Public Query
 
Name  Dr Shubhangi Desai  
Designation  Associate Director, Clinical Operations and Pharmacovigilance  
Affiliation  Abbott Healthcare Pvt. Ltd.  
Address  Department: Clinical Operations, Medical Affairs, Floor 16, Godrej BKC, Plot No. C68, BKC, Near MCA Club, Bandra (E) Mumbai400 051 India Mumbai MAHARASHTRA 400051 India

Mumbai
MAHARASHTRA
400051
India 
Phone  02238160918  
Fax    
Email  shubhangi.desai@abbott.com  
 
Source of Monetary or Material Support  
Abbott Healthcare Private Limited Floor 18, Godrej BKC, Plot No. C – 68, BKC, Near MCA Club, Bandra (E) Mumbai – 400 051  
 
Primary Sponsor  
Name  Abbott Healthcare Private Limited  
Address  Floor 18, Godrej BKC, Plot No. C – 68, BKC, Near MCA Club, Bandra (E) Mumbai400 051 India  
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Adarsh Kumar Garg  Lambda Therapeutic Research Ltd  Clinical Department, Lambda house, Plot no. 38, Survey no. 388, Near Silver Oak Club, S. G. Highway, Gota, Ahmedabad - 382481, Gujarat, India.
Ahmadabad
GUJARAT 
02239536666
02239536665
adarshgarg@lambda-cro.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Independent Ethics Committee-Aditya  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Healthy Human Volunteers  Healthy adult human male subjects between 18 and 45 years of age (both inclusive) with no hypersensitivity or idiosyncratic reaction to Ivabradine or any other similar/ related drugs. 
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Coralan® 7.5 mg (Ivabradine Hydrochloride) Oral Tablets  Each film-coated tablet contains Ivabradine hydrochloride equivalent to Ivabradine 7.5 mg Oral Tablet twice a day at 12 hours apart to be administered to each subject in each period. 
Intervention  Ivabradine 15 mg Oral prolonged release tablet  Each film coated prolonged release tablet contains Ivabradine Hydrochloride Equivalent to Ivabradine 15 mg oral tablet once a day at 12 hours apart to be administered to each subject in each period. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  45.00 Year(s)
Gender  Male 
Details  a)Non smoker, non-alcoholic, healthy adult human male subjects between 18 and 45 years of age (both inclusive) living in and around Ahmedabad city or western part of India.
b)Having a Body Mass Index (BMI) between 18.5 and 30 (both inclusive), calculated as weight in kg / height in m2.
c)Subject weight should be more than 50 kg at the time of screening.
d)Not having any significant diseases or clinically significant abnormal findings during screening, medical history, clinical examination, laboratory evaluations, 12-lead ECG and X-ray chest (Postero-anterior view) recordings.
e)Able to understand and willing to comply with the study procedures, in the opinion of the Principal investigator.
f)Subjects who are able and willing to give written informed consent.
 
 
ExclusionCriteria 
Details  a)Known hypersensitivity or idiosyncratic reaction to Ivabradine or any other similar/ related drugs.
b)History or presence of any disease or condition which might compromise the haemopoietic, renal, hepatic, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal or any other body system.
c)Sitting blood pressure less than 110 /70 mm Hg and pulse rate less than 70 or more than 100 beats per minute at the time of screening
d)Presence of orthostatic hypotension.
e)If the QTc interval will be more than 450 ms on ECG measurement at the time of screening.
f)History of major surgery within 4 weeks prior to receiving study medicine in period-I.
g)Ingestion of a medication (including prescribed and/or non-prescribed, systemic and/or topical medication including herbal supplements/medicines) at any time within14 days prior to dosing of Period-I. In any such case subject selection will be at the discretion of the Principal Investigator.
h)Any history or presence of asthma (including aspirin induced asthma) or nasal polyp or NSAIDs induced urticaria.
i)A recent history of harmful use of alcohol (less than 2 years), i.e. alcohol consumption of more than 14 standard drinks per week (A standard drink is defined as 360 ml of beer or 150 ml of wine or 45 ml of 40% distilled spirits, such as rum, whisky, brandy etc) or consumption of alcohol or alcoholic products within 48 hours prior to receiving study medicine in period-I.
j)Smokers, or who have smoked within last six months prior to start of the study.
k)Consumption of grapefruit or grapefruit products within a period of 72 hours prior to dosing in period-I.
l)The presence of clinically significant abnormal laboratory values during screening.
m)Use of any recreational drugs or history of drug addiction or testing positive in pre-study drug scans.
n)History or presence of psychiatric disorders.
o)A history of difficulty in donating blood.
p)Donation of blood (1 unit or 350 mL) or receipt of an investigational medicinal product or participation in a drug research study within 90 days prior to receiving the first dose of study medicine. Elimination half-life of the study drug should be taken into consideration for inclusion of the subject in the study.
Note: In case the blood loss was less than or equal to 200 mL; subject may be enrolled 60 days after blood donation or after the last sample of previous study.
q)A positive hepatitis screen including hepatitis B surface antigen and/or HCV antibodies.
r)A positive test result for HIV (I & II) antibody.
s)An unusual diet, for whatever reason (e.g. low-sodium), for four weeks prior to receiving the IMP in Period-I. In any such case subject selection will be at the discretion of the Principal Investigator.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Pharmacy-controlled Randomization 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To study relative bioavailability after single oral administration of once daily test product versus twice oral administration of reference product at 12 hours apart under fasting and fed conditions in healthy human male subjects.  The venous blood samples to be withdrawn pre-dose (0.000 hour) and at 0.250, 0.500, 0.750, 1.000, 1.333, 1.667, 2.000, 2.500, 3.000, 4.000, 6.000, 8.000, 10.000, 12.000, 12.250, 12.500, 12.750, 13.000, 13.333, 13.667, 14.000, 14.500, 15.000, 16.000, 18.000, 20.000, 22.000, 24.000, 36.000 and 48.000 hours post-dose following drug administration in each period.  
 
Secondary Outcome  
Outcome  TimePoints 
To assess the safety and tolerability of Ivabradine following single oral administration of once daily test product versus twice oral administration of reference product at 12 hours apart in healthy human male subjects.  The venous blood samples will be withdrawn pre-dose (0.000 hour) and at 0.250, 0.500, 0.750, 1.000, 1.333, 1.667, 2.000, 2.500, 3.000, 4.000, 6.000, 8.000, 10.000, 12.000, 12.250, 12.500, 12.750, 13.000, 13.333, 13.667, 14.000, 14.500, 15.000, 16.000, 18.000, 20.000, 22.000, 24.000, 36.000 and 48.000 hours post-dose following drug administration in each period.  
 
Target Sample Size   Total Sample Size="14"
Sample Size from India="14" 
Final Enrollment numbers achieved (Total)= "14"
Final Enrollment numbers achieved (India)="14" 
Phase of Trial   Phase 1 
Date of First Enrollment (India)   07/10/2016 
Date of Study Completion (India) 05/11/2016 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   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 study is being conducted to study relative bioavailability after single oral administration of once daily Ivabradine prolonged release tablet 15 mg versus twice oral administration of  Coralan® 7.5 mg (Ivabradine Hydrochloride) Tablets at 12 hours apart under fasting and fed conditions in healthy human male subjects.

The study shows that Test Product-T
when compared to the Reference Product-R, meets the relative bioavailability criteria with respect to AUC0-t and AUC0-∞ for Ivabradine under fasting and fed conditions and also demonstrated that the test and the reference products were well tolerated. There were no AEs during the conduct of the study. 

 
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