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CTRI Number  CTRI/2021/08/035346 [Registered on: 03/08/2021] Trial Registered Prospectively
Last Modified On: 28/09/2021
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Randomized, Crossover Trial 
Public Title of Study   Comparative bioavailability study between Remdesivir oral solution and Remdesivir for injection in healthy adult 
Scientific Title of Study   A randomised, single dose, open label, three-period, cross-over, comparative bioavailability study between the test product, Remdesivir oral solution 100 mg/5 mL (Cipla Ltd., India) and the reference product, CIPREMI (Lyophilised) Remdesivir for injection 100 mg/ vial) (Cipla Ltd., India) in healthy adult male human subjects under fasting conditions. 
Trial Acronym  21-04-099 
Secondary IDs if Any  
Secondary ID  Identifier 
21-04-099 Version 01 Date 30 Apr 2021  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Muneesh Garg 
Designation  Principal Investigator 
Affiliation  Sitec Labs Limited 
Address  PEE-DEE Infotech, Plot No. Gen-40, TTC MIDC, Near Nelco, Behind Millennium Business Park, Mahape

Thane
MAHARASHTRA
400710
India 
Phone  919833913773  
Fax    
Email  muneesh.garg@siteclabs.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Hemant Joshi 
Designation  Senior Manager 
Affiliation  Cipla Ltd  
Address  Clinical Research and Development R and D Centre North Block LBS Marg Vikhroli West

Mumbai
MAHARASHTRA
400083
India 
Phone  919823066463   
Fax    
Email  hemant.joshi2@cipla.com  
 
Details of Contact Person
Public Query
 
Name  Mr Milind Gole 
Designation  Director 
Affiliation  Cipla Ltd  
Address  Clinical Research and Development R and D Centre North Block LBS Marg Vikhroli West

Mumbai
MAHARASHTRA
400083
India 
Phone  919819071190  
Fax    
Email  Milind.Gole@Cipla.com  
 
Source of Monetary or Material Support  
Cipla House, Peninsula Business Park, Ganpatrao Kadam Marg, Lower Parel, Mumbai-400013, Maharashtra, India 
 
Primary Sponsor  
Name  Cipla Ltd India  
Address  Cipla House, Peninsula Business Park, Ganpatrao Kadam Marg, Lower Parel, Mumbai-400013, Maharashtra, India  
Type of Sponsor  Pharmaceutical industry-Indian 
 
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 Muneesh Garg  Sitec Labs Ltd.  PEE-DEE Infotech, Plot No. Gen-40, TTC MIDC, Near Nelco, Behind Millennium Business Park, Mahape, Navi Mumbai
Thane
MAHARASHTRA 
919833913773

muneesh.garg@siteclabs.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Suraksha Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Healthy Human Volunteers  healthy adult between 18 to 45 years of age who have a Body Mass Index between 18.5 and 30 kg/m2 weighing not less than 45 kg 
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Remdesivir for injection 100 mg/vial single dose of 100 mg   Remdesivir for injection 100 mg, single dose of 100 mg Frequency: Once Route: Intravenous Duration: 120 minutes 
Intervention  Remdesivir oral solution 100 mg/5 mL Single oral dose of 100 mg  Remdesivir oral solution 100 mg/5 mL(Cipla Ltd., India),Single oral dose of 100 mg, Frequency: Once Route: Oral Duration: NAP 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  45.00 Year(s)
Gender  Male 
Details  1. Volunteers who give consent by signing the informed consent form after understanding the study related information about the nature, risk, and scope of the clinical study as well as the expected adverse effects of the drug.
2. Volunteers who are healthy adult between 18 to 45 years of age (both inclusive) of Asian Indian origin.
3. Volunteers who have a Body Mass Index between 18.5 and 30 kg/m2, weighing not less than 45 kg.
4. Volunteers who have no evidence of any significant diseases or clinically significant abnormal findings during the pre-study screening, medical and medication histories, vital signs examination, physical examination, 12-lead electrocardiogram (ECG) and chest X-ray (postero-anterior view recorded in last 180 days).
5. Volunteers, whose urine alcohol test and urine test for drugs of abuse are negative and whose Rapid Plasma Reagin (RPR), Hepatitis B Surface Antigen (HBsAg), Hepatitis C (Anti HCV) and antibodies to human immuno-deficiency Virus (HIV) I and II are negative or non-reactive.
6. Volunteers whose pre-study screening laboratory tests are within normal limit or clinically not significant.
7. Volunteers who have agreed to follow the appropriate distancing, all the necessary safety precautions like wearing mask, using hand sanitizer etc. during the study.
8. Volunteers who agree to abstain from consuming grapefruit or its products for at least 72 hours prior to dosing and until the last blood sample collection of each study period.
9. Volunteers who agree to abstain from consuming citrus fruits or their products and xanthine containing products (chocolate, tea, coffee or cola drink), for at least 24 hours prior to dosing and until the last blood sample collection of each study period.
10. Volunteers who do not have history of drug addiction or a habit of heavy drinking which is defined as regular intake of more than 2 units of alcohol per day for males (1 unit is equal to 150 mL of wine or 360 mL of beer or 45 mL of 40 percent alcohol) and those who agree to abstain from consuming alcohol or alcoholic products for at least 48 hours prior to dosing and until the last blood sample collection of each study period.
11. Volunteers who are non-smokers or those who are ex-smokers and have less than a 10 pack-year history of smoking and have not consumed tobacco or tobacco containing products for at least 12 months prior to screening and who agree to abstain from the same until the last blood sample collection of the last treatment period.
12. Volunteers must agree to be available for the entire study and have the ability to understand and communicate effectively with the investigators and study personnel.
13. Volunteers whose test for COVID-19 is negative
 
 
ExclusionCriteria 
Details  1. Volunteers who have history of known hypersensitivity to Remdesivir or related class of drug.
2. Volunteers with history of a known food allergy.
3. Volunteers who have vital signs abnormalities (systolic blood pressure less than 100 or greater than 140 mm of Hg or diastolic blood pressure less than 60 or greater than 90 mm of Hg or pulse rate less than 50 beats per minute or more than 100 beats per minute) during pre-study screening and vital signs examination before check-in.
4. Volunteers having any medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract.
5. Volunteers who have recent history of dehydration from diarrhoea, vomiting or any other reason within a period of 24 hours prior to the study check-in.
6. Volunteers having Estimated Glomerular Filtration Rate (eGFR) less than 60 mL/min/1.73 m2 calculated by MDRD (Modification of Diet in Renal Disease Study) formula.
7. Volunteers who have clinically significant signs and symptoms or history of respiratory, cardiovascular, gastrointestinal, dermatological, neurological, psychiatric, genitourinary, endocrinological, musculoskeletal, bleeding disorder, tumor/ cancer, eye, ear, nose and throat disease.
8. Volunteer with febrile illness within 1 week before start of the study.
9. Volunteers who have suffered any clinically significant illness in the 2 weeks prior to dosing or who have been hospitalised within 3 months preceding the start of the study.
10. Volunteers who have taken any drug that induces/inhibits the hepatic microsomal enzymes (including chloroquine phosphate and hydroxychloroquine sulfate) within 30 days prior to dosing.
11. Volunteers who have taken any prescription medication or over-the-counter products available (including vitamins and products from natural origin such as ayurvedic, unani, siddha and homeopathic medicines) and topical medication meant for systemic absorption, within the 7 days prior to dosing.
12. Volunteers who have depot injection or an implant of any drug within 3 months prior to dosing.
13. Volunteers who have a history of difficulty in donating blood.
14. Volunteers who have donated blood (1 unit or 350 mL) within 90 days prior to dosing.
15. Volunteers who have taken any investigational product or participated in any drug research study requiring blood donation within 90 days prior to dosing.
16. Volunteers who have unsuitable veins for repeated venepuncture, evidence of skin lesions on forearm or signs of venepuncture on the forearm suggestive of recent blood donation or participation in a study.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Pre-numbered or coded identical Containers 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
AUC 0 t and AUC 0 inf for Remdesivir  Predose, 0.25, 0.33, 0.50, 0.67, 1.00, 1.33, 1.67, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00, 24.00, 48.00, 72.00, 96.00 and 120.00 hours post-dose 
 
Secondary Outcome  
Outcome  TimePoints 
Cmax,Tmax, T1 by 2, Residual area, Kel, Vd, Cl for Remdesivir
AUC 0 t and AUC 0 inf, Cmax,Tmax, T1 by 2, Residual area, Kel, Vd, Cl for GS 441524 and GS 704277 (metabolite) 
Predose, 0.25, 0.33, 0.50, 0.67, 1.00, 1.33, 1.67, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00, 24.00, 48.00, 72.00, 96.00 and 120.00 hours post-dose 
 
Target Sample Size   Total Sample Size="16"
Sample Size from India="16" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)
Modification(s)  
09/08/2021 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="0"
Months="2"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Other (Terminated) 
Publication Details   none 
Individual Participant Data (IPD) Sharing Statement

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

Response - NO
Brief Summary   This study is A randomised, single dose, open label, three-period, cross-over, comparative bioavailability study between the test product, Remdesivir oral solution 100 mg/ 5 mL (Cipla Ltd., India) and the reference product, CIPREMI (Lyophilised) Remdesivir for injection 100 mg/ vial) (Cipla Ltd., India) in healthy adult male human subjects under fasting conditions. Safety of the study subjects will also be monitored and evaluated. Remdesivir is available as an injection for treatment of Covid 19. Cipla proposed to develop oral formulation to increase compliance and ease of administration of the medication. As per data available in literature Remdesivir has near complete first pass effect. Hence period one and two will be conducted to evaluate the bioavailability of oral Remdesivir. 
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