Comparison Bioequivalence Study: Pre-filled Syringe (Reference) Versus Auto-injection Device (Test)

Study Overview
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Brief Summary
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To compare the bioavailability of a single 400 mg dose of certolizumab pegol solution (2 x 200mg subcutaneous injections) injected either by a pre-filled syringe (reference) or by an auto-injection device (test).

Official Title
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Open Label, Randomized, Parallel Group, Single Dose, 2-way Comparison Bioequivalence Study of Certolizumab Pegol Solution Injected Either by a Pre-filled Syringe (Reference) or by an Auto-injection Device (Test) to Healthy Volunteers.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Certolizumab pegol
* Drug: Certolizumab pegol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-55 years. A Body mass Index (BMI) of 18 to 28 kg/m Good physical and mental health status determined on the basis of the medical history and a general clinical examination Electrocardiogram and clinical laboratory tests interpreted as normal QuantiFERON-TB test negative female subjects: medically accepted method of contraception Exclusion Criteria: prohibited concomitant medication administered vaccines and immunoglobulins in the month preceding the certolizumab pegol injection history of significant disease, allergies history of drug and/or alcohol abuse hepatic enzyme inducing drug within 2 months before study drug administration any drugs having influence of the immune response and antibiotic in the month preceding the inclusion known to be intolerant to PEG previously received certolizumab pegol previously received an antibody product within 5-half lives of the antibody or within 3 months of the start of the study history of tuberculosis have serum hepatitis or is carrier of the Hepatitis B surface antigen (HBs Ag), or Hepatitis C antibody or who is HIV positive

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pre-filled Syringe<br>pre-filled syringe (reference) | Drug: Certolizumab pegol<br>* Pre-filled syringe (reference) containing 1 mL of certolizumab pegol liquid formulation, 200 mg/mL; 2 injections<br>* Other names: CZP;|
| Experimental: Auto-injection Device<br>Auto-injection device (test) | Drug: Certolizumab pegol<br>* Auto-injection device (test) containing 1 mL of certolizumab pegol liquid formulation, 200 mg/mL; 2 injections<br>* Other names: CZP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Drug Concentration-time Curve From Time 0 to Infinity (AUC) |  | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 
| Area Under the Plasma Drug Concentration-time Curve From Time 0 to the Last Quantifiable Point (AUC(0-t)) |  | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 
| Maximum Plasma Concentration (Cmax) |  | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Point Where Log-linear Elimination Phase Begins (TLIN) | TLIN describes timepoint for start of elimination phase determined on the basis of a linear regression model of the log-transformed concentration data. | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 
| Lowest Quantifiable Concentration Time (LQCT) |  | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 
| Apparent Terminal Elimination Rate Constant (λz) |  | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 
| Apparent Terminal Elimination Half-life (t1/2) |  | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 
| Time Corresponding to Cmax (Tmax) |  | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 
| Apparent Total Body Clearance (CL/F) |  | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 
| Apparent Volume of Distribution (Vz/F) |  | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 
| Number of Subjects With Anti-certolizumab Pegol Antibody Plasma Level >2.4 Units/mL |  | After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12 | 
| Injection Pain Assessment on a Visual Analog Scale (VAS) Per Formulation and Per Time Point as Well as Change From Baseline (=Immediately After Injection) at One Hour After Injection | Visual Analog Scale (VAS) ranges from 0 (no pain at all) to 100 mm (max. pain). | Immediately after injection and 1 hour after injection | 
| Injection Questionnaire Per Formulation and Per Time Point - Afraid of Needles | Categorized answer ranges from not at all to extremely. | Before and 24 hours post-dose | 
| Injection Questionnaire Per Formulation and Per Time Point - Afraid of Having Injections | Categorized answer ranges from not at all to extremely. | Before and 24 hours post-dose | 
| Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Pain | Categorized answer ranges from not at all to extremely. | Immediately after injection, 1 h and 24 h after injection | 
| Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Burning Sensation | Categorized answer ranges from not at all to extremely. | Immediately after injection, 1 hour and 24 hours after injection | 
| Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Cold Sensation | Categorized answer ranges from not at all to extremely. | Immediately after injection, 1 hour and 24 hours after injection | 
| Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Itching | Categorized answer ranges from not at all to extremely. | Immediately after injection, 1 hour and 24 hours after injection | 
| Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Redness | Categorized answer ranges from not at all to extremely. | Immediately after injection, 1 hour and 24 hours after injection | 
| Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Swelling | Categorized answer ranges from not at all to extremely. | Immediately after injection, 1 hour and 24 hours after injection | 
| Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Bruising | Categorized answer ranges from not at all to extremely. | Immediately after injection, 1 hour and 24 hours after injection | 
| Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Hardening | Categorized answer ranges from not at all to extremely. | Immediately after injection, 1 hour and 24 hours after injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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certolizumab pegol, Cimzia, bioequivalence, Comparison Bioequivalence Study