Study of Belimumab Administered Subcutaneously to Healthy Subjects - Full Text View

Purpose

The purpose of this study is to measure the amount of belimumab in the blood when given as an injection under the skin (subcutaneously; SC) and to evaluate the safety and tolerability of multiple injections under the skin in healthy subjects.

Condition	Intervention	Phase
Healthy	Biological: Single Dose Group: Belimumab IV 240 mg Biological: Single Dose Group: Belimumab SC 2 x 120 mg Biological: Single Dose Group: Belimumab SC 1 x 240 mg Biological: Single Dose Group: Belimumab SC 1 x 200 mg Biological: Multiple Dose Group: Belimumab SC 2 x 120 mg weekly Biological: Multiple Dose Group: Belimumab SC 1 x 200 mg weekly	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomized, Parallel-Group, Open-Label Study to Evaluate the Absolute Bioavailability, Pharmacokinetics, Tolerability and Safety of a High Concentration Formulation of Belimumab (HGS1006), a Fully Human Monoclonal Anti-BLyS Antibody, Administered Subcutaneously to Healthy Subjects

Resource links provided by NLM:

Drug Information available for: Belimumab

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Time to Reach Maximum Serum Drug Concentration (Tmax) Following a Single Dose of Belimumab Given as Intravenous Infusion (IV) or Subcutaneous Injection (SC) [ Time Frame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70 ] [ Designated as safety issue: No ]
Maximum Serum Drug Concentration (Cmax) Following a Single Dose of Belimumab Given as IV or SC [ Time Frame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70 ] [ Designated as safety issue: No ]
Area Under the Serum Drug Concentration-time Curve From Time 0 to Infinite Time (AUC0-∞) Following a Single Dose of Belimumab Given as IV or SC [ Time Frame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70 ] [ Designated as safety issue: No ]
AUC (0-∞) = Area under the serum drug concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-last) plus C (last)/λz. C (last) is the last measurable concentration. λz was determined by linear regression (r2 ≥ 0.8) with uniform weighting of all data in the terminal linear portion of the log-transformed drug concentration-time profile.
Terminal Elimination Half-life (t1/2,Term) Following a Single Dose of Belimumab Given as IV or SC [ Time Frame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70 ] [ Designated as safety issue: No ]
Terminal elimination half-life is the time measured for the serum drug concentration of belimumab to decrease by one half.
Absolute Bioavailability of a Single Dose of Belimumab Given as IV or SC [ Time Frame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70 ] [ Designated as safety issue: No ]
Bioavailability (F) is a measurement of the rate and extent to which a drug reaches the systemic circulation. The bioavailability of belimumab administered by IV is compared to the bioavailability of belimumab administered via single-SC injection.

Secondary Outcome Measures:

Time to Reach Maximum Serum Drug Concentration (Tmax) Following Weekly (x 4) SC Injections of Belimumab [ Time Frame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119 ] [ Designated as safety issue: No ]
Maximum Serum Drug Concentration (Cmax) Following Weekly (x 4) SC Injections of Belimumab [ Time Frame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119 ] [ Designated as safety issue: No ]
Area Under the Serum Drug Concentration-time Curve From Time 0 to Infinite Time (AUC0-∞) Following Weekly (x 4) SC Injections of Belimumab [ Time Frame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119 ] [ Designated as safety issue: No ]
AUC (0-∞) = Area under the serum drug concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-last) plus C (last)/λz. C (last) is the last measurable concentration. λz was determined by linear regression (r2 ≥ 0.8) with uniform weighting of all data in the terminal linear portion of the log-transformed drug concentration-time profile.
Terminal Elimination Half-life (t1/2,Term) Following Weekly (x 4) SC Injections of Belimumab [ Time Frame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119 ] [ Designated as safety issue: No ]
Terminal elimination half-life is the time measured for the serum drug concentration of belimumab to decrease by one half.
Absolute Bioavailability of Weekly (x 4) SC Injections of Belimumab [ Time Frame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119 ] [ Designated as safety issue: No ]
Bioavailability (F) is a measurement of the rate and extent to which a drug reaches the systemic circulation. The bioavailability following weekly (x 4) SC injections of belimumab was calculated by comparing the bioavailability of belimumab administered IV to the bioavailability of belimumab administered via 4 weekly SC injections.
Number of Participants Who Experienced Adverse Events [ Time Frame: Up to Day 119 ] [ Designated as safety issue: Yes ]
Includes AEs reported in participants from the first dose of belimumab throughout the study through Day 70/Exit (single dose groups) or Day 119/Exit (multiple dose groups).

Enrollment:	118
Study Start Date:	February 2011
Study Completion Date:	September 2011
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Belimumab IV 240 mg	Biological: Single Dose Group: Belimumab IV 240 mg Belimumab IV 240 mg administered on Day 0 Other Name: BENLYSTA™
Experimental: Belimumab SC 2 x 120 mg	Biological: Single Dose Group: Belimumab SC 2 x 120 mg Belimumab SC 120 mg x 2 injections (equal to 240 mg) administered immediately one after the other on Day 0 Other Name: BENLYSTA™
Experimental: Belimumab SC 1 x 240 mg	Biological: Single Dose Group: Belimumab SC 1 x 240 mg Belimumab SC 240 mg x 1 injection on Day 0 Other Name: BENLYSTA™
Experimental: Belimumab SC 1 x 200 mg	Biological: Single Dose Group: Belimumab SC 1 x 200 mg Belimumab SC 200 mg x 1 injection on Day 0 Other Name: BENLYSTA™
Experimental: Belimumab SC 2 x 120 mg weekly	Biological: Multiple Dose Group: Belimumab SC 2 x 120 mg weekly Belimumab 120 mg x 2 injections (equal to 240 mg) administered immediately one after the other on Days 0, 7, 14, and 21 Other Name: BENLYSTA™
Experimental: Belimumab SC 1 x 200 mg weekly	Biological: Multiple Dose Group: Belimumab SC 1 x 200 mg weekly Belimumab 200 mg x 1 injection administered on Days 0, 7, 14, and 21 Other Name: BENLYSTA™

Detailed Description:

This study is designed to evaluate the absolute bioavailability, pharmacokinetics, tolerability, and safety of a single dose (groups 1-4) or multiple doses (groups 5-6) of belimumab administered subcutaneously (SC) to healthy subjects.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Key Inclusion Criteria:

Healthy subjects defined as no clinically relevant abnormalities identified by a detailed medical history, full physical exam, 12-lead electrocardiogram (ECG), and clinical laboratory tests.
Body weight between 45 to 120 kg (99 to 264 lbs).
Must agree to use effective contraception throughout the study and for 14 weeks after administration of belimumab.
Have the ability to understand the requirements of the study, provide written informed consent, and comply with the study protocol procedures.

Key Exclusion Criteria:

Pregnant or nursing.
Test positive for drugs or alcohol or have had a drug or alcohol dependence within the past year.
Have used any prescription medicines within the past 30 days or herbal/botanical supplements within the past 7 days or anticipate use during the study. May use prescription contraceptives, hormone replacement therapy, and over-the-counter medicines such as antihistamines or nutritional support such as vitamins, minerals, or amino acids.
Have received a live vaccine within the past 30 days or anticipate receipt of a live vaccine during the study and within 4 months after last injection of belimumab.
Have a history of an allergic or anaphylactic reaction to drugs, food, or insect bite or sting requiring medical intervention.
Have a history of allergic reaction to contrast agents or biological medicines.
Have participated in a clinical trial and received an experimental medicine within the past 60 days.
Have received treatment with a B cell targeted therapy at any time.
Have required management of an infection within the past 14 days.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01583530

Locations

United States, Florida

Daytona Beach, Florida, United States
United States, Indiana

Evansville, Indiana, United States
United States, Texas

Dallas, Texas, United States
United States, Wisconsin

Madison, Wisconsin, United States

Sponsors and Collaborators

Human Genome Sciences Inc., a GSK Company

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )
ClinicalTrials.gov Identifier:	NCT01583530 History of Changes
Other Study ID Numbers:	HGS1006-C1105
Study First Received:	April 20, 2012
Results First Received:	May 22, 2012
Last Updated:	October 29, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

Belimumab
Injections, Subcutaneous
Drug Administration Routes
Injections
Lupus Erythematosus, Systemic
Lupus
SLE

Systemic Lupus Erythematosus
Antibodies
Autoimmune Disease
Biological Therapy
Immune System Diseases
Pharmacokinetics
Biological Availability

ClinicalTrials.gov processed this record on May 23, 2013