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CTRI Number  CTRI/2015/02/005524 [Registered on: 11/02/2015] Trial Registered Prospectively
Last Modified On: 06/02/2015
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Other 
Public Title of Study   A randomized, double-blind, two-treatment, single-period, single-dose, parallel design, comparative bioavailability study between RTPR- 021 (test adalimumab) and Humira® (reference adalimumab). 
Scientific Title of Study   A randomized, double-blind, two-treatment, single-period, single-dose, parallel design, comparative bioavailability study between RTPR- 021 (test adalimumab) 40 mg/0.8 ml prefilled syringe from Reliance Life Sciences Pvt. Ltd., India and Humira® (reference adalimumab) 40 mg/0.8 ml prefilled syringe from Abbott biotechnology Germany in healthy, adult, human subjects following subcutaneous administration under fasting condition. 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
RLS/0814/044; Version 1.0, Dated: 18th Sep 2014  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Suresh Maroli 
Designation  Head of Clinical pharmacology unit 
Affiliation  Reliance Life Sciences Pvt. Ltd. 
Address  Reliance Life Sciences Pvt. Ltd. Dhirubhai Ambani Life Sciences Centre (DALC), Plot R-282, TTC Area of MIDC, Rabale, Navi Mumbai 400701, India

Mumbai
MAHARASHTRA
400701
India 
Phone  912267678731  
Fax  912267678299  
Email  Suresh.Maroli@relbio.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Pravin Ghadge  
Designation  Head, Medical writing and Pharmacovigilance 
Affiliation  Reliance Life Sciences Pvt. Ltd. 
Address  Reliance Life Sciences Pvt. Ltd. Dhirubhai Ambani Life Sciences Centre (DALC), Plot R-282, TTC Area of MIDC, Rabale, Navi Mumbai 400701, India

Mumbai
MAHARASHTRA
400701
India 
Phone  912267678431  
Fax  912267678299  
Email  pravin.ghadge@relbio.com  
 
Details of Contact Person
Public Query  
Name  Mr Deepak Narayanswamy 
Designation  Project Manager  
Affiliation  Reliance Life Sciences Pvt. Ltd. 
Address  Dhirubhai Ambani Life Sciences Centre (DALC), Plot R-282, TTC Area of MIDC, Rabale, Navi Mumbai 400701, India

Mumbai
MAHARASHTRA
400701
India 
Phone  912267678820  
Fax  912267678299  
Email  deepak.narayanswamy@relbio.com  
 
Source of Monetary or Material Support  
Reliance Life Sciences Pvt. Ltd. Dhirubhai Ambani Life Sciences Centre, Plot R-282 TTC Area of MIDC, Rabale, Navi Mumbai 400 701 India.  
 
Primary Sponsor  
Name  Reliance Life Sciences Pvt Ltd 
Address  Dhirubhai Ambani Life Sciences Centre, Plot R-282 TTC Area of MIDC, Rabale, Navi Mumbai 400 701 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 Suresh Maroli  Reliance Life Sciences Pvt. Ltd.  Dhirubhai Ambani Life Sciences Centre, Plot R-282 TTC Area of MIDC, Rabale, Navi Mumbai 400 701.
Mumbai
MAHARASHTRA 		 9004094132
02240678299
Suresh.Maroli@relbio.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Healthy Human Volunteers  Comparative bioavailability study in healthy, adult human subjects. 
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Humira® (reference adalimumab) 40 mg/0.8 ml prefilled syringe from Abbott biotechnology, Germany   Dosage form: Solution for injection Route of administration: subcutaneous administration  
Intervention  R-TPR-021 (test adalimumab) 40 mg/0.8 ml prefilled syringe developed by Reliance Life Sciences Pvt. Ltd., India   Dosage form: Solution for injection Route of administration: subcutaneous administration Dosage: Single subcutaneous injection of 40mg Adalimumab Frequency: Single dose  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  45.00 Year(s)
Gender  Both 
Details  1. Healthy adult male and female subjects, aged between 18 to 45 years (both inclusive).
2. Subjects with Body Mass Index (BMI) 18 to 24.9 kg/m2
3. If subject is a female and is
- of child bearing potential, she should be practicing an acceptable method of birth
control for the duration of the study as judged by the investigator(s), such as condoms,
foams, jellies, diaphragm, intrauterine device (IUD), or abstinence
OR
- surgically sterile, bilateral tubal ligation should be documented
4. Subjects able and willing to comply with the protocol requirements.
5. Subjects willing to voluntarily provide written informed consent.
6. Subjects willing to undergo pre and post-study physical examinations and laboratory investigations.
7. Subjects who are non-smokers based on history.
8. Subjects willing to adhere to the protocol and the following study requirements:
• Should not consume xanthine containing products, such as coffee, tea, chocolate or soft drinks at least 48 hours prior to dosing (i.e. in-house monitoring and the remaining based on history) until the last sample collection.
• Should not consume alcohol at least 48 hours prior to dosing (i.e. during in-house monitoring and the remaining based on history) until the last sample collection.
• Should not consume grapefruit or its products at least 7 days prior to dosing (i.e. during in-house monitoring and the remaining based on history) and until the last sample collection
9. Subjects having no clinically significant medical history and no clinically significant abnormalities in general physical examination, laboratory assessments, ECG, chest X-Ray or vital signs.
 
 
ExclusionCriteria 
Details  1. Subjects incapable of understanding the informed consent process.
2. Pregnant female subjects with a positive pregnancy test at screening or positive serum β-HCG test or lactating females.
3. Female subjects of childbearing potential who are unwilling or unable to use an appropriate method of contraception as outlined in the inclusion criteria, at least 14 days prior to the first dose of study medication until the post-study follow-up (i.e. until 60 days after the drug administration). Use of hormonal contraceptives that are either oral or implants will not be acceptable.
4. Subjects with inadequate venous access in their left or right arm to allow the collection of all samples via venous cannula in the study.
5. Subjects with abnormalities in resting heart rate (100 beats/min or 50 beats/min), blood pressure either hypotensive episode (systolic blood pressure 90 mmHg or diastolic blood pressure 60 mmHg) or hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥90 mmHg), oral temperature ( 95.60F or 990F) on the screening day.
6. Subjects with active history of psychiatric disorders, which are likely to limit the validity of consent to participate in the study, or limit the ability to comply with the protocol requirements.
7. Subjects with any evidence of organ dysfunction or any clinically significant deviation from normal in their physical or clinical evaluation including ECG and X-ray results.
8. Subjects who have taken over the counter or prescribed medications, including any enzyme modifying drugs or any systemic medication within 30 days prior to the start of the clinical period and during the study period.
9. Subjects with a known history of drug hypersensitivity to adalimumab or any excipients of the formulation.
10. Subjects with a history of alcohol abuse and/or drug abuse or who are found urinary screen test positive for drugs of abuse (Amphetamines, Morphine, Benzodiazepines, Marijuana, Cocaine and Barbiturates) or are found with current alcohol abuse based on alcohol breath test.
11. Subjects diagnosed to be HIV 1 and 2 or Hepatitis B (HBsAg) or Hepatitis C (HCV) virus positive.
12. Subjects with clinically significant abnormal haematological values [haemoglobin (Hb), total white blood cells count (WBC), total red blood cells count (RBC), differential WBC count, platelet count and hematocrit].
13. Subjects with history of active infection in last 1 month.
14. Subjects with clinically significant abnormal laboratory values for serum creatinine, blood urea nitrogen (BUN), serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum alkaline phosphatase (ALP), serum bilirubin, serum glucose (fasting), serum cholesterol and serum electrolytes.
15. Subjects with clinically significant abnormal urine analysis, defined as the presence of RBC (5/HPF), pus cells (5/HPF), epithelial cells (5/HPF), glucose (positive), ketones (positive), bilirubin (positive) and protein (positive) (unless the clinical investigator considers the deviation to be irrelevant for the purpose of the study).
16. Subjects with a clinically significant past history or current medical condition of:
a. Pulmonary disorders (COPD and asthma)
b. Cardiovascular disorders (especially heart blocks including second or third degree A-V block and right bundle branch block, myocardial infarction, congestive heart failure, uncontrolled hypertension, cardiogenic shock and asymptomatic premature ventricular contractions and/or asymptomatic non-sustained ventricular tachycardia)
c. Neurological disorders (especially epileptic seizures)
d. GIT disorders (gastrointestinal bleeding, gastric/peptic ulcer)
e. Renal and/or hepatic disorders
f. Coagulation disorders
g. Endocrine disorders (especially diabetes mellitus)
17. Subjects who participated in any other clinical investigation using experimental drugs or have bled more than 300 mL in the past 3 months.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
To establish bioequivalence of Test vs Reference product in relation to the rate and extent of absorption on the basis of the following pharmacokinetic parameters:
• Cmax
• AUC0-t
 		 Primary Outcome will be assessed at following time points: Day 1 to Day 4, 8, 10, 14, 21, 28, 35, 42 and 51. 
 
Secondary Outcome  
Outcome  TimePoints 
To monitor adverse events, including clinically significant laboratory parameters
2. Frequency of formation of antibodies to adalimumab
• Immunogenicity assessment at 0, 312, 648, 984, 1200 hrs post drug administration
3. To determine the following pharmacokinetic parameters of Test and Reference product
• AUC0-∞
• tmax
• t1/2
• Kel
• MRT0–t,
• MRT0–∞
• CL
 		 To monitor adverse events, including clinically significant laboratory parameters
2. Frequency of formation of antibodies to adalimumab
• Immunogenicity assessment at 0, 312, 648, 984, 1200 hrs post drug administration
3. To determine the following pharmacokinetic parameters of Test and Reference product
• AUC0-∞
• tmax
• t1/2
• Kel
• MRT0–t,
• MRT0–∞
• CL
 
 
Target Sample Size   Total Sample Size="120"
Sample Size from India="120" 
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)   23/02/2015 
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="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details    
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary  

Adalimumab is a tumor necrosis factor (TNF) blocker indicated for treatment of Rheumatoid Arthritis (RA).  Many pro-inflammatory cytokines including TNF alpha, chemokines, and growth factors are expressed in Rheumatoid diseased joints. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in the synovial fluid of rheumatoid arthritis patients and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of rheumatoid arthritis.

 

Adalimumab binds specifically to TNF-alpha and blocks its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface TNF expressing cells in vitro in the presence of complement. Adalimumab does not bind or inactivate lymphotoxin (TNF-beta).  Rapid reduction in cellularity and  inflammation in the rheumatoid synovium after TNF-antagonist therapy is likely the result of dampening of TNF-driven cytokine and chemokine cascades and hence  TNF blocker therapy like Adalimumab will be helpful in Rheumatoid arthritis

M/s Reliance Life Sciences Pvt. Ltd., (RLS) has indigenously developed the biosimilar version of Humira®. This study is being conducted with a view to generate comparative bioavailability data on the product. This will help in making correlations between the bioavailability profile of the drug and its clinical effects. Also, the data will contribute to Reliance’s overall global drug development program for Adalimumab.

 

The proposed Phase I study is a randomized, double-blind, two-treatment, single-period, single-dose, parallel design, comparative bioavailability study between R-TPR-021 (test adalimumab) 40 mg/0.8 ml prefilled syringe from Reliance Life Sciences Pvt. Ltd., India and Humira® (reference adalimumab) 40 mg/0.8 ml prefilled syringe from Abbott biotechnology Germany in healthy, adult, human subjects following subcutaneous administration under fasting condition. 
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