Compare Actions in Healthy Volunteer of 50 mg Etanercept Injection Using an Auto-injector Device and Manual Injection

Study Overview
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Brief Summary
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The purpose of the study is to compare Pharmacokinetics of liquid etanercept that is administered to healthy subjects aged 18-55 by an auto-injector device and manual injection (each subject received both injections).

Detailed Description
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This single-center, randomized, open-label, 2-period, 2-sequence, 2-treatment, crossover study in healthy men and women compared the pharmacokinetics (PK) and safety profiles of two 50-mg subcutaneous (SC) injections of etanercept liquid (in a 1.0-mL prefilled syringe): (1) using a disposable auto-injector device, and (2) using a standard manual injection. Each subject received both injections in the abdomen, separated by a washout period of 28 days.

Official Title
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An Open-label, Randomized, 2-period Crossover Study to Compare the Pharmacokinetics of a 50-mg Dose of Liquid Etanercept Administered to Healthy Subjects by Subcutaneous Injection Using an Auto-Injector Device and Manual Injection

Conditions
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Healthy Men and Women

Intervention / Treatment
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* Device: Auto-injector device
* Other: Etanercept (ENBREL®) via Manual injection
* Drug: Etanercept (ENBREL®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healty men and women Aged 18-55 years at time of screening BMI 18-31 kg/m2 inclusive Free of any clinically significant disease Willing to reside in research facility 4 consecutive nights 2 times and to attend follow up visits Willing to sign consent Negative HIV, hepatitis B and C, and urine pregnancy tests Exclusion Criteria: Unstable medical condition (hospitalized within 30 days, myocardial infarction or major surgery within 6 months, or seizure within 12 months of study day 1) Current active infecton, history of infections, or condition which may predispose infection (such as diabetes) Clinically significant abnormality in laboratory samples done while screening history of tuberculosis donated blood within 30 days of screening Use of prescription or over-the-counter medication during the study/ History of smoking or use of tobacco within 30 days of screening Positive urine scree for alcohol or drugs of abuse at screening or the day prior to dosing Unwilling to pracitce contraception for the duration ot the study Any other condition which could interfere with obtaining data required by the protocol

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A-etanercept (ENBREL®) by auto-injector<br>Single dose of etanercept (ENBREL®) in a pre-filled syringe administered with an auto-injector device manufactured by Scandinavian Health Limited (SHL) | Device: Auto-injector device<br>* Single 50 mg subcutaneous dose of liquid etanercept (ENBREL®) in a 1.0 ml pre-filled syringe administered via an auto-injector device manufactured by Scandinavian Health Limited (SHL)<br>Drug: Etanercept (ENBREL®)<br>* Single 50 mg subcutaneous dose of liquid etanercept (ENBREL®) in a 1.0 ml pre-filled syringe administered via an auto-injector device manufactured by Scandinavian Health Limited (SHL)<br>|
| Other: B-etanercept (ENBREL®) by Manual injection<br>Single dose of etanercept (ENBREL®) in a syringe given by manual injection (reference treatment) | Other: Etanercept (ENBREL®) via Manual injection<br>* Single 50 mg subcutaneous dose of liquid etanercept (ENBREL®) in a 1.0 ml pre-filled syringe administered via manual injection (reference treatment) to compare to the auto-injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of the geometric means of etanercept by auto-injector to etanercept by manual injection for the PK parameter of AUC (0-t) | 28 days after receiving treatment in Period 1, subjects return to the facility on an outpatient basis to receive the alternate treatment in Period 2. Procedures performed in the first period are repeated in the second period. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile PK parameters of AUC (0-∞) | PK parameters of the area under the serum drug concentration-time curve from time zero to infinity | 28 days: timepoint at which outcome measure is assessed following each treatment arm | 
| Safety Events measured by adverse events and how they relate to study drug | Incidence, severity, and relationship to study drug of adverse events for each subject | 28 days-timepoint at which outcome measure is assessed following each treatment arm | 
| Measure of vital signs changes from baseline to end of each treatment period | Changes from baseline in vital signs (includes blood pressure-systolic and diastolic; and heart rate per minute) and physical examinations | Baseline and 28 days following each treatment | 
| Any Clinically Significant changes in clinical laboratory tests will be noted | Laboratory variables summarized separately from adverse events and compared to normal ranges; samples will be analyzed by standard procedures | Collected at screening, Day -1, Day 4 after dosing each treatment period, and on day 15 after dosing in Period 2 | 
| Blood samples obtained to measure seroreactivitiy to etanercept at baseline and following treatment | Blood samples collected to measure seroreactivity to etanercept | Predose in each treatment period and 28 days following dosing in treatment period B | 
| Profile PK parameters of AUC (C max ) | maximum observed concentration | 28 days: timepoint at which outcome measure is assessed following each treatment arm | 
| PK parameters of the area under the serum drug concentration (t 1/2) | terminal phase half-life | 28 days: timepoint at which outcome measure is assessed following each treatment arm | 
| PK parameters of the area under the serum drug concentration (t z) | terminal phase half-life | 28 days: timepoint at which outcome measure is assessed following each treatment arm | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PK, etanercept, healthy subject, open-label, randomized, auto-injection, pharmacokinetic