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

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.

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).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Certolizumab pegol; Drug: Certolizumab pegol

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rennes, France

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pre-filled Syringe; pre-filled syringe (reference)	Drug: Certolizumab pegol; Auto-injection device (test) containing 1 mL of certolizumab pegol liquid formulation, 200 mg/mL; 2 injections; Other Names: CZP; CDP870; Cimzia®; Drug: Certolizumab pegol; Pre-filled syringe (reference) containing 1 mL of certolizumab pegol liquid formulation, 200 mg/mL; 2 injections; Other Names: CZP; CDP870; Cimzia®
Experimental: Auto-injection Device; Auto-injection device (test)	Drug: Certolizumab pegol; Auto-injection device (test) containing 1 mL of certolizumab pegol liquid formulation, 200 mg/mL; 2 injections; Other Names: CZP; CDP870; Cimzia®; Drug: Certolizumab pegol; Pre-filled syringe (reference) containing 1 mL of certolizumab pegol liquid formulation, 200 mg/mL; 2 injections; Other Names: CZP; CDP870; Cimzia®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: UCB Pharma

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: February 13, 2009
• First Submitted That Met QC Criteria: February 17, 2009
• First Posted (Estimate): February 18, 2009

Study Record Updates

• Last Update Posted (Estimate): August 31, 2011
• Last Update Submitted That Met QC Criteria: August 30, 2011
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: bioequivalence; Cimzia; certolizumab pegol; Comparison Bioequivalence Study
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Certolizumab Pegol
• Other Study ID Numbers: C87045