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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Certolizumab pegol

• Registration Number: NCT00845663
• Lead Sponsor: UCB Pharma

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10
• Primary Completion: 2008-04
• Study Completion: 2008-04
• Study First Submitted: 2009-02-13
• Study First Submitted QC: 2009-02-17
• Study First Posted: 2009-02-18
• Results First Submitted: 2009-08-25
• Results First Submitted QC: 2009-10-08
• Results First Posted: 2009-11-17
• Status Verified: 2009-12
• Last Update Submitted: 2011-08-30
• Last Update Posted: 2011-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 98

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Auto-injection Device	Certolizumab pegol	Auto-injection device (test)
Pre-filled Syringe	Certolizumab pegol	pre-filled syringe (reference)

Primary Outcome Measures

Name	Time	Method
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
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

Secondary Outcome Measures

Name	Time	Method
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
Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Pain	Immediately after injection, 1 h and 24 h after injection	Categorized answer ranges from not at all to extremely.
Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Burning Sensation	Immediately after injection, 1 hour and 24 hours after injection	Categorized answer ranges from not at all to extremely.
Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Itching	Immediately after injection, 1 hour and 24 hours after injection	Categorized answer ranges from not at all to extremely.
Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Redness	Immediately after injection, 1 hour and 24 hours after injection	Categorized answer ranges from not at all to extremely.
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
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	Immediately after injection and 1 hour after injection	Visual Analog Scale (VAS) ranges from 0 (no pain at all) to 100 mm (max. pain).
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
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
Injection Questionnaire Per Formulation and Per Time Point - Afraid of Needles	Before and 24 hours post-dose	Categorized answer ranges from not at all to extremely.
Time Point Where Log-linear Elimination Phase Begins (TLIN)	After 12 and 24 hours, on day 3, 4, 5, 6, 7, 10, after week 2, 3, 4, 6, 8, 12	TLIN describes timepoint for start of elimination phase determined on the basis of a linear regression model of the log-transformed concentration data.
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
Injection Questionnaire Per Formulation and Per Time Point - Afraid of Having Injections	Before and 24 hours post-dose	Categorized answer ranges from not at all to extremely.
Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Bruising	Immediately after injection, 1 hour and 24 hours after injection	Categorized answer ranges from not at all to extremely.
Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Hardening	Immediately after injection, 1 hour and 24 hours after injection	Categorized answer ranges from not at all to extremely.
Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Cold Sensation	Immediately after injection, 1 hour and 24 hours after injection	Categorized answer ranges from not at all to extremely.
Injection Site Reaction Questionnaire Per Formulation and Per Time Point - Swelling	Immediately after injection, 1 hour and 24 hours after injection	Categorized answer ranges from not at all to extremely.