A Single Dose Pharmacokinetics (PK) Study of GSK2434735 in Healthy Male Volunteers

Study Overview
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Brief Summary
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An exploratory First Time in Human (FTIH) study investigating the pharmacokinetics, immunogenicity, safety and tolerability of GSK2434735 administered as a single low dose in healthy male subjects

Detailed Description
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Interleukin-13 (IL-13) and IL-4 are mediators in the pathogenesis of established asthmatic disease. GSK2434735 is a bispecific antibody to IL-13 and IL-4. The purpose of this open label, sequential cohort, exploratory First Time in Human (FTIH) study is to evaluate the pharmacokinetics (PK) profile of GSK2434735 after a single low intravenous or subcutaneous dose in healthy male volunteers, and to assess if the pharmacokinetics (PK) parameters can be scaled from monkey to man. In addition, the safety and tolerability will be monitored and the study will assess if antibodies are generated to GSK2434735.

Official Title
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An Exploratory First Time in Human (FTIH) Study Investigating the Pharmacokinetics (PK), Immunogenicity, Safety and Tolerability of GSK2434735 Administered as a Single Low Dose in Healthy Male Subjects

Conditions
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Asthma

Intervention / Treatment
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* Drug: Intravenous (IV) single dose
* Drug: Subcutaneous (SC) single dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers between 18 and 65 years of age Negative for pre-existing antibodies to GSK2434735. Body weight greater than and equal to 50 kg BMI 19 - 29.9 kg/m2. Lifelong non-smokers or ex-smokers of greater than 6 months Exclusion Criteria: Clinically significant abnormalities. Current or past history of significant cardiac, respiratory, metabolic, renal, hepatic, neurological or gastrointestinal conditions. Current evidence or recent history of an infective illness. Vaccination within 3 weeks of screening History of severe allergic reactions, angio-oedema, anaphylaxis or immunodeficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 GSK2434735<br>Cohort 1: Single intravenous administration of GSK2434735 and Pharmacokinetic (PK) and Immunogenicity assessments up to 42 days post dose. | Drug: Intravenous (IV) single dose<br>* GSK2434735 administered as a single intervenous dose at the beginning of the study<br>* Other names: GSK2434735;|
| Experimental: Cohort 2 GSK2434735<br>Cohort 2: Single subcutaneous administration of GSK2434735 and Pharmacokinetic (PK) and Immunogenicity assessments up to 42 days post dose. | Drug: Subcutaneous (SC) single dose<br>* GSK2434735 administered as a single subcutaneous dose at the beginning of the study<br>* Other names: GSK2434735;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of Pharmacokinetics | Cmax, tmax, AUC, CL, t1/2 | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of GSK2434735 as assessed by telemetry and change from baseline in 12-lead Electrocardiograms (ECG) | Change from baseline for PR, RR, QRS, QT, QTc measurements at Day 42 | 42 days | 
| Safety and tolerability of GSK2434735 as assessed by change from baseline in blood pressure and heart rate | Change from baseline for systolic and diastolic blood pressure and heart rate measurements at 42 Days | 42 days | 
| Safety and tolerability of GSK2434735 as assessed by number of participants with adverse events | Clinically relevant changes from baseline in subject's disposition at Day 42 | 42 days | 
| Change from baseline for Clinical laboratory assessments (hematology, chemistry and urinalysis | Changes from baseline values of hematologic , chemistry and urinary testing parameters at Day 42 | 42 days | 
| Assessment of human anti-drug antibodies (ADA) in blood | Incidence of human anti-drug antibodies (ADA) at Day 42 | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunogenicity, GSK2434735, pharmacokinetics (PK), PK, biospecific antibody