A comparative study to conduct in Normal Healthy Volunteers to establish similarity for 3 products of Tocilizumab: Dr.Reddyâ??s Tocilizumab/RoActemra(Tocilizumab)/Actemra (Tocilizumab).
- Registration Number
- CTRI/2022/03/041200
- Lead Sponsor
- Dr Reddys Laboratories Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 141
1.Healthy male volunteers, 18 to 50 years (both inclusive) of age
2.In general good health as determined by a qualified physician based on a comprehensive medical history, physical examination including vital signs, laboratory hematology, clinical chemistry, urinalysis and 12-lead ECG before randomisation
3.Body mass index between 18.5-30.0 kg/m2 (both inclusive) and body weight of 50.0 â?? 90.0 kg (both inclusive)
4.Have all screening results (vital signs, physical examination, clinical laboratory tests, 12-lead ECG, thyroid function etc.) within the normal range or outside the normal range but assessed as clinically non-significant by the Investigator unless the value constitutes an explicit exclusion criterion.
5.Volunteers must be willing to abstain from sexual intercourse or willing to use adequate contraception in all relationships with a partner from the opposite sex a condom for the male partner and another form of contraception (such as an intra-uterine device, barrier method with spermicide, oral contraceptive, injectable progesterone, sub-dermal implant) for the female partner from the time of screening until 3 months after the dosing date unless one of the partners is infertile or surgically sterile.
6. Capable, and amenable to providing written informed consent to the study requirements
7.Willing to stay on study restrictions throughout the study duration
1.Positive test result for Quantiferon- TB Gold test, syphilis, hepatitis B, hepatitis C, or HIV-1 or 2.
2.Live virus vaccination within 3 months prior to screening or intention to receive live virus vaccination during the trial or up to 3 months after the administration of the study drug.
3.Any prior exposure to tocilizumab or to any other agents directly acting on interleukin-6 or on its receptors including investigational products.
4. History of immunodeficiency or other clinically significant immunological disorders, or auto-immune disorders, ongoing or frequent/ recurring infection defined as more than 3/year requiring treatment or prior herpes zoster not fully healed (including the post-herpetic neuralgia period if occurring) within one year prior to randomisation or history of systemic fungal infection at any time.
5.Allergy or hypersensitivity to any recombinant human or humanized antibodies, other therapeutic proteins or any excipients in the study formulations.
6.History and/or current presence of clinically significant (in the opinion of the Investigator) atopic allergy, hypersensitivity or allergic reactions.
7.Blood donation, participation in any study requiring repeated blood sampling or haemorrhage requiring treatment or any transfusion in the past 3 months.
8.Screening or baseline (day -1) blood pressure higher than 140 mm Hg (systolic) or higher than 90 mm Hg (diastolic) or subjects currently on anti-hypertensive drugs. Up to two repeats in different days are allowed and, in this case, the mean of the measurements will be used to decide on eligibility. Screening blood pressure is to be measured in the sitting position after 5 minutes rest on the same.
9.History of relevant orthostatic hypotension, fainting spells, or blackouts.
10.QTc (Fridericia correction) longer than 450 milliseconds.
11.History or presence of any clinically relevant nervous system disease including, but not restricted to any stroke/TIA or of seizures other than febrile seizures before the age of 5 years.
12.History of and/or current gastrointestinal, renal, endocrine, pulmonary, hepatic, cardiovascular (including history of or presence of angina, exertional dyspnea, orthopnea, congestive heart failure or myocardial infarction and thrombotic or embolic episode requiring treatment), haematological (including pancytopenia, aplastic anemia or blood dyscrasia and coagulopathies or an INR higher than 1.5), metabolic (including known diabetes mellitus) considered as significant by the investigator. This criterion includes any disorder or condition that, in the Investigatorâ??s opinion, may interfere with the safety of the subject, the study evaluations or the subject compliance to the study procedures and limitations
13.ALT or AST higher than 1.25 times the ULN (a single repeat in a different day is allowed).
14.Absolute Neutrophil count below 2 x 109/liter (2000 per mm3) or platelet count below 100 x 109/liter (100000 per mm3). A single repeat in a different day is allowed.
15.Clinically relevant hyperlipidaemia (fasting serum LDL-cholesterol higher than 190 mg/dL or fasting serum triglycerides higher than 220 mg/dL or subject currently on antihyperlipidaemic drugs). A single repeat in a different day is allowed.
16.Any active infection, even if minor, ongoing at the time of screening or dosing.
17.Presence of any non-healed wound or bone f
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To demonstrate pharmacokinetic similarity of DRL_TCTimepoint: A total of 20 blood samples (3.5 mL each) will be collected from each subject during the study for PK assessment. Pre-dose (0.00) and the post dose samples will be collected at 0.50 h after start of infusion (SOI), 1.00 h, and at 2.00 h, 3.00 h, 5.00 h, 13.00 h and, 25.00 h after SOI and on days 3 (49.00h), 5 (97.00h), 8 (169.00h), 11 (241.00h), 15 (337.00h), 22 (505.00h), 29 (673.00h), 36 (841.00h), 43 (1009.00h), 50 (1177.00h), 57 (1345.00h) and 64(1513.00h) post study drug SOI
- Secondary Outcome Measures
Name Time Method To evaluate pharmacodynamics (PD), safety, tolerability and immunogenicityTimepoint: â?¢Pharmacokinetic parameters: AUC(0-infinity), Cmax, tmax, terminal elimination rate constant Kel, volume of distribution at steady state â??Vss and CL; AUC%extrap will be reported to ensure proper coverage of AUC by the sampling schedule. <br/ ><br>â?¢Pharmacodynamic parameters of IL-6 (calculated by standard non-compartmental methods): maximum effect (Emax) with and without baseline correction and area under the effect curve (AUEC) (effect is value minus baseline, thus baseline correction implicit).