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1 Clinical Trial Details (PDF Generation Date :- Sun, 21 Apr :29:03 GMT) CTRI Number Last Modified On 06/02/2015 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study CTRI/2015/02/ [Registered on: 11/02/2015] - Trial Registered Prospectively No BA/BE Other A randomized, double-blind, two-treatment, single-period, single-dose, parallel design, comparative bioavailability study between RTPR- 021 (test adalimumab) and Humira (reference adalimumab). 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., 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. Secondary IDs if Any Secondary ID Identifier Details of Principal Investigator or overall Trial Coordinator (multi-center study) Details Contact Person (Scientific Query) Details Contact Person (Public Query) RLS/0814/044; Version 1.0, Dated: 18th Sep 2014 Designation Affiliation Protocol Number Details of Principal Investigator Dr Suresh Maroli Phone Fax Designation Affiliation Head of Clinical pharmacology unit Reliance Life Sciences Pvt. Ltd. Reliance Life Sciences Pvt. Ltd. Dhirubhai Ambani Life Sciences Centre (DALC), Plot R-282, TTC Area of MIDC, Rabale, Navi , Suresh.Maroli@relbio.com Details Contact Person (Scientific Query) Dr Pravin Ghadge Phone Fax Designation Affiliation Head, Medical writing and Pharmacovigilance Reliance Life Sciences Pvt. Ltd. Reliance Life Sciences Pvt. Ltd. Dhirubhai Ambani Life Sciences Centre (DALC), Plot R-282, TTC Area of MIDC, Rabale, Navi , pravin.ghadge@relbio.com Details Contact Person (Public Query) Mr Deepak Narayanswamy Project Manager Reliance Life Sciences Pvt. Ltd. Dhirubhai Ambani Life Sciences Centre (DALC), Plot R-282, TTC page 1 / 6

2 Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Sites of Study Details of Ethics Committee Regulatory Clearance Status from DCGI Health Condition / Problems Studied Intervention / Comparator Agent Inclusion Criteria Phone Fax Area of MIDC, Rabale, Navi , 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 Type of Sponsor NIL List of Countries of Principal Investigator Dr Suresh Maroli Primary Sponsor Details Reliance Life Sciences Pvt Ltd Dhirubhai Ambani Life Sciences Centre, Plot R-282 TTC Area of MIDC, Rabale, Navi Pharmaceutical industry-n NIL of Site Site Phone/Fax/ Reliance Life Sciences Pvt. Ltd. Dhirubhai Ambani Life Sciences Centre, Plot R-282 TTC Area of MIDC, Rabale, Navi Suresh.Maroli@relbio.c om of Committee Approval Status Date of Approval Is Independent Ethics Committee? Institutional Ethics Committee Status Approved 18/10/2014 No Date Approved/Obtained 14/01/2015 Health Type Healthy Human Volunteers Condition Comparative bioavailability study in healthy, adult human subjects. Type Details Intervention Comparator Agent R-TPR-021 (test adalimumab) 40 mg/0.8 ml prefilled syringe developed by Reliance Life Sciences Pvt. Ltd., Humira (reference adalimumab) 40 mg/0.8 ml prefilled syringe from Abbott biotechnology, Germany Inclusion Criteria Dosage form: Solution for injection Route of administration: subcutaneous administration Dosage: Single subcutaneous injection of 40mg Adalimumab Frequency: Single dose Dosage form: Solution for injection Route of administration: subcutaneous administration page 2 / 6

3 Age From Age To Gender Year(s) Year(s) 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. Exclusion Criteria Details Exclusion Criteria 1. Subjects incapable of understanding the informed consent process. 2. Pregnant female subjects with a positive pregnancy test at screening or positive serum?-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 page 3 / 6

4 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 Method of Concealment Blinding/Masking Computer generated randomization Not Applicable 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. page 4 / 6

5 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 Phase of Trial Date of First Enrollment () Date of First Enrollment (Global) Estimated Duration of Trial Recruitment Status of Trial (Global) Recruitment Status of Trial () Publication Details Brief Summary Total Sample Size=120 Sample Size from =120 N/A 23/02/2015 No Date Specified Years=1 Months=0 Days=0 Not Applicable Not Yet Recruiting 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. page 5 / 6

6 Powered by TCPDF ( 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., 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. page 6 / 6