Healthy Men and Women
Conditions
Keywords
etanercept, healthy subject, open-label, randomized, PK, auto-injection, pharmacokinetic
Brief summary
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
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.
Interventions
DEVICEAuto-injector device
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)
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
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)
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Events measured by adverse events and how they relate to study drug | 28 days-timepoint at which outcome measure is assessed following each treatment arm | Incidence, severity, and relationship to study drug of adverse events for each subject |
| Measure of vital signs changes from baseline to end of each treatment period | Baseline and 28 days following each treatment | Changes from baseline in vital signs (includes blood pressure-systolic and diastolic; and heart rate per minute) and physical examinations |
| Any Clinically Significant changes in clinical laboratory tests will be noted | Collected at screening, Day -1, Day 4 after dosing each treatment period, and on day 15 after dosing in Period 2 | Laboratory variables summarized separately from adverse events and compared to normal ranges; samples will be analyzed by standard procedures |
| Profile PK parameters of AUC (0-∞) | 28 days: timepoint at which outcome measure is assessed following each treatment arm | PK parameters of the area under the serum drug concentration-time curve from time zero to infinity |
| Profile PK parameters of AUC (C max ) | 28 days: timepoint at which outcome measure is assessed following each treatment arm | maximum observed concentration |
| PK parameters of the area under the serum drug concentration (t 1/2) | 28 days: timepoint at which outcome measure is assessed following each treatment arm | terminal phase half-life |
| PK parameters of the area under the serum drug concentration (t z) | 28 days: timepoint at which outcome measure is assessed following each treatment arm | terminal phase half-life |
| Blood samples obtained to measure seroreactivitiy to etanercept at baseline and following treatment | Predose in each treatment period and 28 days following dosing in treatment period B | Blood samples collected to measure seroreactivity to etanercept |
Outcome results
None listed