Open-label Study Using 50 Mg Liquid Etanercept Subcutaneous Injection in the Thigh to Compare an Auto-injector Device and a Manual Injection in Healthy Subjects

Study Overview
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Brief Summary
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A single-center, open-label, randomized study with a screening period of up to 21 days. Following that, eligible men and women will receive 50 mg of etanercept subcutaneously in the thigh to compare injection by auto-injection device to manual injection (each injection separated by 28 days)

Detailed Description
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A single-center, open-label, 2-period, 2-sequence, 2-treatment, randomized, crossover study. After a screening period of up to 21 days before dosing, 36 eligible men and women will be assigned to receive a 50-mg subcutaneous (SC) dose of etanercept administered by each of 2 methods of injection (Treatment A: administration by auto-injector device; and Treatment B: administration by manual injection) on separate occasions in an order determined by a randomization list (randomized 1:1 to sequence). Treatment administrations will be separated by a minimum of 28 days (maximum of 36 days). Subjects will be required to remain resident during the 72-hours after dosing in each period.

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

Conditions
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Healthy Men and Women

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between the age of 18 and 45 years, inclusive at the time of screening Body mass index (BMI) between 19 and 30 kg/m2, inclusive at the time of screening Absence of clinically significant physical examination findings as determined by the investigator and free of any clinically significant disease or condition that requires care by a physician that would interfere with the study evaluation or procedures 12-lead ECG (reporting ventricular rate and PR, QRS, QT and QTc intervals) within normal limits or clinically acceptable to the investigator Negative human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), and hepatitis C antibody (HepCAb) status at the time of screening Negative pregnancy test for all women at screening and the day before dosing Willing to reside in the research facility for 3 consecutive nights, on two occasions, and willing to return to research facility for scheduled follow-up visits Before any study specific procedures or administration of study medication, the subject must sign the Institutional Review Board (IRB)-approved informed consent form Exclusion Criteria: Unstable medical condition, defined as having been hospitalized within 30 days, myocardial infarction within 6 months, major surgery within 6 months, or a seizure within 12 months of study day 1, or otherwise unstable in the judgment of the investigator (i.e., at risk of complications or adverse events unrelated to study participation) Clinically significant abnormality in chemistry, hematology, or urinalysis parameters performed at screening as determined by the investigator Current active infection, including chronic or localized infection or history of recurring infections with underlying condition that may predispose one to infection (e.g., diabetes) Known history of active tuberculosis Donated blood or blood products within 12 weeks before day -1, or a total of 1500 mL within 1 year before day -1 Known hypersensitivity to etanercept or any excipients Use of any prescription or over-the-counter medication within 7 days before day -1 without the approval of the investigator (with the exception of vitamins, topical medications, contraceptive medications, or hormonal replacement therapy in postmenopausal women) Consumption of alcohol within 48 hours before dosing Known history of drug or alcohol abuse within 1 year of screening Positive urine screen for alcohol and/or potential drugs of abuse, at screening, and the day before dosing Smoked more than 10 cigarettes per day within the 12 months before day -1 Women who are nursing or lactating Unwilling or unable to practice an adequate barrier method of contraception (e.g., condom, barrier method contraceptive with spermicide, IUD, etc.), as determined by the investigator, for the duration of the study Use of an investigational agent, drug, and/or device within 30 days of screening Any other condition that might reduce the chance of obtaining data (e.g., known poor compliance) required by the protocol or that might compromise the ability to give informed consent

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: Treatment A-etanercept (ENBREL®) via auto-injector device<br>Single dose of etanercept (ENBREL®) in a pre-filled syringe administered with an auto-injector device manufactured by Scandinavian Health Limited (SHL) | Device: etanercept (ENBREL®) via 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>|
| Other: Treatment B-etanercept (ENBREL®) via 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 mean of etanercept (ENBREL®) administered by auto-injector Scandinavian Health Limited-SHL) to etanercept administered by manual injection for the pharmacokinetic (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. Blood samples are collected pre-dose and after dosing for both treatment periods. | 28 days following each treatment arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary includes the pharmokinetic parameter to measure the etanercept (ENBREL®) AUC (0-x), area under the curve | 28 days after receiving treatment in Period 1, subjects return to facility to receive the alternate treatment in Period 2. Procedures performed in the first period are repeated in the second period. (Blood samples are collected pre-dose and after dosing for both treatment periods.) | 28 days: timepoint at which outcome measure is assessed following each treatment arm | 
| Safety Events measured by number of adverse events and retationship to treatment | Number of adverse events for each subject summarized by system organ class, severity, and relationship to treatment | 28 days following each treatment arm (total of 77 days including screening) | 
| Any significant changes from baseline in Vital Signs and physical examinations | Change from baselline of vital signs, which includes blood pressure (systolic and diastolic) and heart rate per minute. | Baseline and 28 days following each treatment arm (total of 77 days including screening) | 
| Any Clinically Significant changes in clinical laboratory tests will be noted. | Clinically significant abnormalities in clinical laboratory tests (chemistry and hematology and urine) analyzed by standard procedures | Collected screening, Day -1 in both treatment periods, and day 15 in treatment period 2 | 
| 12-lead Electrocardiograms will be performed and saved with subject source records | Standard 12-lead electrocardiogram (ECG) with review of ventricular rate, rhythm, and interval measurements and appearance of the ECG waves will be performed | Performed at screening and day 15 in Treatment B | 
| Blood samples obtained to measure seroreactivitiy to etanercept at baseline and following treatment | Blood samples to measure seroreactivity to etanercept | Predose in each treatment period and 28 days following dosing in treatment period B | 
| Secondary includes measure of pharmacokinetic parameter of Tmax, the time to reach maximum concentration | Subjects return to the facility 28 days following each treatment segment (blood samples are collected immediately pre-dose and after dosing) | 28 days following each treatment period the outcome will be measured | 
| Secondary outcome to measure t 1/2: elimination half-life for etanercept | Subjects return to the facility 28 days following dosing; blood samples are taken immediately pre-dose and after treatment | Outcome to be measured 28 days following each treatment | 
| Secondary to include etanercept pharmacokinetic parameter of CL/F: apparent clearance | Subjects return to facility 28 days following each treatment; blood sample is obtained immediately pre-dose and after dosing | Measurement assessed at 29 day timepoint following each treatment arm | 

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