Japanese phase1 Study of Belimumab (IV vs SC)

Study Overview
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Brief Summary
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This study is an open-label, randomized, 2 parallel group, single dose study in healthy Japanese males to assess the pharmacokinetics and safety/tolerability of single intravenous administration and single subcutaneous administration of GSK1550188. Serial blood samples for the determination of GSK1550188 concentration will be collected and safety assessments will be performed for each treatment group

Official Title
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An Open Label, Randomized, Parallel, Single Dose Study to Investigate Safety and Pharmacokinetics Following Intravenous Administration and Subcutaneous Administration of GSK1550188 in Healthy Japanese Males

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: GSK1550188 IV
* Drug: GSK1550188 SC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy as defined as being free from clinically significant illness or disease as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital sign, laboratory tests and ECG. Rationale: Set for the appropriate selection of healthy males Japanese healthy male between 20 and 55 years of age inclusive, at the time of signing the informed consent. Rationale: Set for the appropriate evaluation of safety and pharmacokinetics of GSK1550188 in healthy Japanese males Body weight greater than and equal to 50.0 kg and BMI within the range 18.5 more than and equal to - less than 25.0 kg/m2. Rationale: To include those who have a standard figure based on the obesity criteria of the Obesity Association in Japan, these ranges are established Non-smoker or ex-smoker having ceased smoking for at least 6 months. Rationale: Set for the appropriate evaluation of safety and pharmacokinetics of GSK1550188 in healthy Japanese males AST, ALT, alkaline phosphatase and total bilirubin less than and equal to ULN at screening. Rationale: Set for the appropriate evaluation of safety and pharmacokinetics of GSK1550188 in healthy Japanese males Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Rationale: Set in consideration of ethics of the study in accordance with GCP. Single QTc [QTcF] less than 450 msec. Rationale: Set for the appropriate evaluation of safety and pharmacokinetics of GSK1550188 in healthy Japanese males Exclusion Criteria: A positive test for syphilis, Hepatitis B surface antigen, Hepatitis B surface antibody, Hepatitis B core antibody, or positive Hepatitis C antibody, HIV antigen /antibody, HTLV-1 antibody at screening. Rationale: Set for the appropriate selection of healthy subjects and in consideration of safety of the staff that handle or measure the blood samples. A positive pre-study drug screen at screening. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. History of regular alcohol consumption exceeding, on average, 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 350 mL of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits) within 6 months of screening. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. The subject had participated in a clinical study or post-marketing study with an investigational or a non-investigational product during the previous 4 months preceding the administration of study medication of this study. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. Exposure to more than four new chemical entities within 12 months prior to the dosing day. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. The subject planned to concurrently participate in another clinical study or post-marketing study. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days or 5 half-lives (whichever is longer) prior to the administration of study medication. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy excluding pollen allergy without current symptoms. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. Where participation in the study would result in donation of blood or blood products in excess of 400 mL within 4 month or 200 mL within 2 months. Unwillingness or inability to follow the procedures outlined in the protocol. Rationale: Set to secure study quality Subject is mentally or legally incapacitated. Rationale: Set to secure study quality Subjects with ECG results considered clinically significant by the investigator. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. Subjects with a supine systolic blood pressure less than 90 mmHg or greater than140 mmHg and/or a supine diastolic blood pressure less than 55 mmHg or greater than 90 mmHg and/or systolic blood pressure drop from supine to standing of greater than 30 mmHg. Rationale: Set in consideration of subjects' safety related to the IV route of administration. Immunoglobulin (M, A, G) level is less than LLN at screening. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. History of anaphylactic reaction to any food, drug, or insect bite/sting. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. History of allergic reaction to parenteral administration of contrast agents, foreign proteins, or monoclonal antibodies. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. History of B cell targeted therapy (rituximab, other anti-CD20agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor fusion protein [BR3], TACI-Fc, LY2127399 [anti-BAFF] or GSK1550188) at any time. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188. History of any infection requiring hospitalization or treatment with antivirals or antibiotics, or vaccination within 30 days prior to administration of study medication. Rationale: To exclude inappropriate subjects for the evaluation of the safety and pharmacokinetics of GSK1550188.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GSK1550188 200mg for SC<br>Single SC dose of belimumab 200mg | Drug: GSK1550188 SC<br>* Single SC dose of belimumab 200mg<br>|
| Active Comparator: GSK1550188 200mg for IV<br>Single IV dose of belimumab 200 mg | Drug: GSK1550188 IV<br>* Single IV dose of belimumab 200 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of Vital signs | Systolic and diastolic blood pressure, pulse rate, body temperature | Day1-Day71 | 
| Change from baseline of biomarkers | CD20+, immunoglobulin | Day-1 - Day71 | 
| Immunogenicity | Presence of anti belimumab antibody | Day0 - Day71 (if necessary, 6-month) | 
| Change from baseline of other safety parameters after single intravenous and subcutaneous administration | ECGs, clinical laboratory test, local tolerance evaluation (injection site), and adverse events | Day-1 - Day71 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite (or profile) of pharmacokinetics after single intravenous administration | Percentage of AUC(0-inifinity) obtained by extrapolation (%AUCex), Time of last quantifiable concentration (tlast), Systemic clearance of parent drug (CL), Volume of distribution after IV/SC administration (Vz), Volume of distribution after IV administration at steady state (Vss), Terminal phase rate constant (λz), Mean residence time(MRT) | Day1-Day71 | 
| Composite (or profile) of pharmacokinetics after subcutaneous administration | Area under concentration-time curve (AUC) 0-7days, AUC 0-28 days, Percentage of AUC(0-infinity) obtained by extrapolationAUC(0-infinity) (%AUCex), tlast, Apparent clearance following subcutaneous dosing (CL/F), Volume of distribution after IV/SC administration (Vz)/F, λz, MRT | Day-1 - Day71 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK1550188, belimumab, SLE, healthy, Japanese, pharmacokinetics, safety