A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamic of a Single Intravenous Dose of GSK1070806 Administered to Healthy Male and Female Caucasian, Chinese and Japanese Participants Aged 18 to 65 Years of Age Inclusive
Overview
- Phase
- Phase 1
- Intervention
- GSK1070806
- Conditions
- Dermatitis, Atopic
- Sponsor
- GlaxoSmithKline
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- Part A: Serum GSK1070806 area under the concentration-time curve from time zero extrapolated to infinity (AUC[0-∞])
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This study is divided into two parts:
Part A of the study is double blinded, randomized, placebo-controlled and aims to assess the safety, tolerability, pharmacokinetics (PK) and Pharmacodynamic (PD) effect of a single intravenous (IV) infusion dose of GSK1070806 when administered to healthy participants of Japanese, Chinese and European/Caucasian ancestry.
Part B of the study is an open label single cohort arm to assess the safety, tolerability, PK and PD effect of a single IV bolus low dose of GSK1070806 in healthy participants of European/Caucasian ancestry.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring \[12-lead Electrocardiogram (ECGs)\]
- •Between 18 and 65 years of age inclusive, at the time of signing the informed consent
- •Body weight within the range 45 - 100 kilograms (kg) and body mass index (BMI) within the range 18-32 kilogram/meter square (kg/m\^2) (inclusive)
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
- •Is a woman of non-childbearing potential (WONCBP) OR
- •Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective \[with a failure rate of less than 1 percent (\<1%) per year\], with low user dependency
- •Capable of giving signed informed consent
- •Participants of Japanese ancestry are eligible based on meeting all of the following:
- •Healthy male and female participants born in Japan
- •Descendants of four ethnic Japanese grandparents and two ethnic Japanese parents
Exclusion Criteria
- •History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, immunological, metabolic, musculoskeletal or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data
- •Personal or family history of cardiomyopathy
- •Known varicella, herpes zoster, or other severe viral infection within 6 weeks of anticipated dosing on Day
- •Or history of recurrent herpes reactivation in the past 2 years
- •Evidence of active or latent tuberculosis (TB) as documented by medical history, examination, and TB testing with a positive (not indeterminate) QuantiFERON test
- •History or evidence of clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, anaphylaxis, erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis)
- •Lymphoma, leukemia, or any malignancy except for basal cell carcinomas of the skin that have been resected with no evidence of metastatic disease for 5 years
- •Alanine transaminase (ALT) greater than (\>) 1.5x upper limit of normal (ULN)
- •Total bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or previous uncomplicated cholecystectomy more than 3 months ago)
Arms & Interventions
Part A: GSK1070806
Participants in Part A will receive single dose of GSK1070806 intravenous (IV) infusion
Intervention: GSK1070806
Part B: GSK1070806
Participants in Part B will receive single dose of GSK1070806 IV bolus
Intervention: GSK1070806
Part A: Placebo
Participants in Part A will receive single dose of placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Part A: Serum GSK1070806 area under the concentration-time curve from time zero extrapolated to infinity (AUC[0-∞])
Time Frame: Up to Week 24
Part A: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time Frame: Up to Week 24
Part A: Serum GSK1070806 area under the concentration-time curve from time zero to the last quantifiable time (AUC(0-t))
Time Frame: Up to Week 24
Part A: Maximum observed serum concentration (Cmax) of GSK1070806
Time Frame: Up to Week 24
Secondary Outcomes
- Part B: Number of participants with AEs and SAEs(Up to Week 32)
- Part A: Total IL-18 concentrations in serum(Up to Week 24)
- Part B: Total IL-18 concentrations in serum(Up to Week 32)
- Part B: Number of participants with ADA formation(Up to Week 32)
- Part A: Number of participants with anti-drug antibody (ADA) formation(Up to Week 24)