A Study to Investigate the Safety Tolerability Pharmacokinetics, and Pharmacodynamics of Inhaled and Intravenous GSK2862277 in Healthy Volunteers
- Conditions
- Respiratory Disorders
- Interventions
- Drug: Single IV dose of GSK2862277Drug: Matching placebo single dose IHDrug: Repeat IV dose of GSK2862277Drug: Matching placebo repeat dose IV infusionDrug: Matching placebo single dose IV infusionDrug: Single IH dose of GSK2862277Drug: Repeat IH dose selected of GSK2862277 from Part 2Drug: Matching placebo repeat dose IH
- Registration Number
- NCT01818024
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This will be a 3 part study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat doses of GSK2862277 administered via inhalation (IH) or intravenous (IV) routes in healthy subjects.
Part 1 of this study will involve an initial assessment of safety, tolerability and pharmacokinetics of GSK286227, via single escalating intravenous doses, compared to a predecessor molecule, GSK1995057. After completion of Part 1 an interim data review will occur which will assess key comparability criteria to inform progression to Part 2 of the study.
Part 2 of the study will involve single doses of GSK2862277 at a level predicted to be at or close to therapeutic dose levels. Part 2 will investigate both intravenous and inhaled routes of administration, in sequential manner, respectively. An interim data review will also occur after completion of Part 2, where all data accumulated previously will be assessed to examine appropriateness to progress to Part 3.
Part 3 of the study will involve 5 days of repeat dosing via both inhaled and intravenous routes using the same dose administered in Part 2.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Subject is positive at screening for HAVH autoantibodies against GSK1995057 (Part 1 only).
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus (HIV) antibody.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus (HIV) antibody.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part 1: Cohort 1c Single IV dose of GSK2862277 Single IV dose of GSK2862277 as a continuous infusion over 3 hours. Part 2: Cohort 2b Placebo Matching placebo single dose IH Matching placebo will be administered. Part 3: Cohort 3a GSK2862277 Repeat IV dose of GSK2862277 IV dose of GSK2862277 (decided from Part 2) as a continuous infusion over 1 hour for daily 5 days. Part 3: Cohort 3a Placebo Matching placebo repeat dose IV infusion Matching placebo will be administered as IV infusion over 1 hour daily for 5 days. Part 1: Cohort 1a Single IV dose of GSK2862277 Single IV dose of GSK2862277 as a continuous infusion over 2 hours. Part 2: Cohort 2a GSK2862277 Single IV dose of GSK2862277 Single IV dose of GSK2862277 as a continuous infusion over 1 hour. Part 1: Cohort 1b Single IV dose of GSK2862277 Single IV dose of GSK2862277 as a continuous infusion over 3 hours. Part 2: Cohort 2a Placebo Matching placebo single dose IV infusion Matching placebo will be administered as a continuous IV infusion over 1 hour. Part 2: Cohort 2b GSK2862277 Single IH dose of GSK2862277 Single IH dose of GSK2862277. Part 3: Cohort 3b GSK2862277 Repeat IH dose selected of GSK2862277 from Part 2 Repeat IH dose of GSK2862277 (decided from Part 2) daily for 5 days. Part 3: Cohort 3b Placebo Matching placebo repeat dose IH Matching placebo will be administered as IH daily for 5 days.
- Primary Outcome Measures
Name Time Method Safety and tolerability of single IV or IH dose of GSK2862277 assessed by number of subjects with adverse events (AE)s in Part 1 and Part 2 Up to 42 days Safety and tolerability parameters will include recording of adverse events (AEs), throughout the study.
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by number of subjects with AEs in Part 3 Up to 42 days Safety and tolerability parameters will include recording of AEs, throughout the study.
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by vital signs in Part 1 and Part 2 Up to 42 days Vital signs will include blood pressure (BP), heart rate respiration rate and body temperature.
Safety and tolerability of single IV dose of GSK2862277 as assessed by measurement of plasma cytokines in Part 1 Up to 42 days Blood samples will be collected for assessment of plasma cytokines.
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by laboratory tests in Part 1 and Part 2 Up to 42 days Laboratory tests will include haemogram, clinical chemistry, urine examination.
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by vital signs in Part 3 Up to 42 days Vital signs will include BP, heart rate respiration rate and body temperature.
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by ECG in Part 3 Up to 42 days Safety data will include ECG readings obtained at each timepoint during the study.
Safety and tolerability of repeat IV or IH dose of GSK2862277 as assessed by laboratory tests in Part 3 Up to 42 days Laboratory tests will include haemogram, clinical chemistry, urine examination.
Immunogenicity in subjects receiving repeat IV or IH dose of GSK2862277 in Part 3 Up to 60 days Presence of anti GSK2862277 binding antibodies will be evaluated.
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by ECG in Part 1 and Part 2 Up to 42 days Safety data will include electrocardiogram (ECG) readings obtained at each timepoint during the study.
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 1 and Part 2 Up to 42 days Spirometry monitoring will include forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 3 Up to 42 days Spirometry monitoring will include FEV1 and FVC.
Immunogenicity in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2 Up to 60 days Presence of anti GSK2862277 binding antibodies will be evaluated.
- Secondary Outcome Measures
Name Time Method Composite of urine parameters in subjects receiving single IV 2 mg/kg dose of GSK2862277 in Part 2 in Cohort 2a Up to 48 hours post dose The urine samples will be collected for urine concentrations of GSK2862277.
PK parameters in subjects receiving repeat IV dose of GSK2862277 in Part 3 Cohort 3a Up to 48 hours post last dose The blood samples will be collected for plasma concentrations of GSK2862277.
Pharmacokinetic (PK) parameters in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2 Up to 48 hours post dose The blood samples will be collected for plasma concentrations of GSK2862277.
Pharmacodynamic and immune function biomarkers in serum of subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2 Up to 48 hours post last dose The pharmacodynamic and immune function biomarkers in serum.
Change from baseline in IL-8 expression in ex vivo WBA in subjects receiving single IV 0.05 mg/kg dose of GSK2862277 in Part 1 in Cohort1c Up to 12 hours post dose IL-8 expression in ex vivo whole blood essay (WBA).
PK parameters in subjects receiving repeat IH dose of GSK2862277 in Part 3 Cohort 3b Up to 48 hours post last dose The blood samples will be collected for plasma concentrations of GSK2862277
PK parameters in subjects receiving single IV dose of GSK2862277 in Part 1 Up to 48 hours post last dose The PK parameters will be compared with historic GSK1995057 PK data in Part 1
Pharmacodynamic and immune function biomarkers in serum of subjects receiving repeat IV or IH dose of GSK2862277in Part 3 Up to 48 hours post last dose The pharmacodynamic and immune function biomarkers in serum.
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Harrow, Middlesex, United Kingdom