Pharmacokinetic, Safety and Tolerability Study of Altebrel in Healthy Male Subjects

NCT03273088 | Completed Phase 1

• 1 other identifier: ARY.ETA.AJ.PH1.2016
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to demonstrate pharmacokinetic (PK) similarity of biosimilar candidate Altebrel relative to etanercept reference product (Enbrel®) and evaluate safety and tolerability of Altebrel, in a crossover fashion in healthy male volunteers after administration of a single dose (25 mg) of etanercept. The primary objective of this study is to demonstrate that the PK of Altebrel is similar to its originator, Enbrel®, as assessed by the area under the serum concentration time curve (AUC) from time 0 extrapolated to infinity (AUCinf) and the Cmax. The secondary objectives of the study are: To further compare the PK of Altebrel and Enbrel®. To assess the safety of Altebrel.

Conditions

Phase 1; Bioequivalence

Keywords

healthy subjects; Pharmacokinetics; etanercept; single dose; Anti-Inflammatory Agents, Non-Steroidal

Outcome Measures

Primary Outcomes (2)

• Area under the concentration-time curve from time zero to infinity (AUCinf)

  AUCinf will be calculated using the equation:AUCinf= AUClast + (Clast / Kel)

  21 days

• Maximum serum concentration (Cmax)

  It is obtained directly from the observed concentration-time data

  21 days

Secondary Outcomes (2)

• Area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast)

  21 days

• Time to Cmax (Tmax)

  21 days

Study Arms (2)

AryoGen Pharmed etanercept

EXPERIMENTAL

Altebrel (etanercept prefilled syringe produced by AryoGen Pharmed Company) 25mg/0.5ml in prefilled syringe.

Drug: Etanercept

Pfizer etanercept

ACTIVE COMPARATOR

Enbrel® (etanercept prefilled syringe produced by Pfizer Company) 25mg/0.5ml in prefilled syringe.

Drug: Etanercept

Interventions

Etanercept DRUG

A single dose of etanercept (25mg/0.5ml prefilled syringe) was administered subcutaneously to healthy subjects.

Also known as: Altebrel, Enbrel

AryoGen Pharmed etanercept; Pfizer etanercept

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written IC to participate in the trial and to comply with the trial procedures.
• \) Take written informed consent to participate in the trial and to abide by the trial restrictions.
• \) Be healthy male between the ages of 18 and 55 years. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, complete physical examination including blood pressure and heart rate measurement, 12 lead ECG and clinical laboratory tests.
• \) Have a body mass index between 20.0 and 29.9kg/m², inclusive 5) Have Chest X ray with no evidence of current, active TB or previous (inactive) TB, general infections, heart failure, malignancy, or other clinically significant abnormalities taken at Screening or within 24 weeks prior to Day 1 and read by a qualified radiologist

You may not qualify if:

• Being doubtful about their availability to complete the trial.
• history and/or current presence of clinical significant atopic allergy, hypersensitivity or allergic reactions, also including known or suspected clinically relevant drug hypersensitivity to any components of the test and reference IMP formulation or comparable drugs.
• Active or latent Tuberculosis or who have a history of Tuberculosis.
• history of invasive systemic fungal infections or other opportunistic infections
• systemic or local infection, a known risk for developing sepsis and/or known active inflammatory process
• serious infection associated with hospitalisation and/or which required intravenous antibiotics
• history of and/or current cardiac disease
• Have received live vaccine(s) within 30 days prior to Screening or who will require live vaccine(s) between Screening and the final study visit.
• Intake medication with a half-life \> 24 h within 1 month or 5 half-lives of the medication prior to the first administration of IMP.
• Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody. A positive test for HIV antibody.
• History of CNS demyelinating disorders in family (MS)
• Have a history of smoking \>10 cigarettes per day

Sponsors & Collaborators

• AryoGen Pharmed Co.: lead

Study Sites (1)

Orchidpharmed PK/PD site

Tehrān, Tehran Province, Iran

Location

Related Publications (4)

• Lee YJ, Shin D, Kim Y, Kang J, Gauliard A, Fuhr R. A randomized phase l pharmacokinetic study comparing SB4 and etanercept reference product (Enbrel(R)) in healthy subjects. Br J Clin Pharmacol. 2016 Jul;82(1):64-73. doi: 10.1111/bcp.12929. Epub 2016 May 2.

  PMID: 26972584 BACKGROUND

• Yi S, Kim SE, Park MK, Yoon SH, Cho JY, Lim KS, Shin SG, Jang IJ, Yu KS. Comparative pharmacokinetics of HD203, a biosimilar of etanercept, with marketed etanercept (Enbrel(R)): a double-blind, single-dose, crossover study in healthy volunteers. BioDrugs. 2012 Jun 1;26(3):177-84. doi: 10.2165/11631860-000000000-00000.

  PMID: 22515513 BACKGROUND

• Davatchi F, Jamshidi AR, Banihashemi AT, Gholami J, Forouzanfar MH, Akhlaghi M, Barghamdi M, Noorolahzadeh E, Khabazi AR, Salesi M, Salari AH, Karimifar M, Essalat-Manesh K, Hajialiloo M, Soroosh M, Farzad F, Moussavi HR, Samadi F, Ghaznavi K, Asgharifard H, Zangiabadi AH, Shahram F, Nadji A, Akbarian M, Gharibdoost F. WHO-ILAR COPCORD Study (Stage 1, Urban Study) in Iran. J Rheumatol. 2008 Jul;35(7):1384. Epub 2008 May 1.

  PMID: 18464299 BACKGROUND

• Kawai S, Sekino H, Yamashita N, Tsuchiwata S, Liu H, Korth-Bradley JM. The comparability of etanercept pharmacokinetics in healthy Japanese and American subjects. J Clin Pharmacol. 2006 Apr;46(4):418-23. doi: 10.1177/0091270006286435.

  PMID: 16554449 BACKGROUND

MeSH Terms

Interventions

Etanercept

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2017
• First Posted: September 6, 2017
• Study Start: December 4, 2016
• Primary Completion: March 15, 2017
• Study Completion: March 15, 2017
• Last Updated: September 19, 2018

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)