Last updated: 11/07/2018 10:22:24
A Study to Investigate the Safety Tolerability Pharmacokinetics, and Pharmacodynamics of Inhaled and Intravenous GSK2862277 in Healthy Volunteers
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Three Part, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of Inhaled and Intravenous GSK2862277 in Healthy Volunteers
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
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
Timeframe: Up to 42 days
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by number of subjects with AEs in Part 3
Timeframe: Up to 42 days
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by laboratory tests in Part 1 and Part 2
Timeframe: Up to 42 days
Safety and tolerability of repeat IV or IH dose of GSK2862277 as assessed by laboratory tests in Part 3
Timeframe: Up to 42 days
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by vital signs in Part 1 and Part 2
Timeframe: Up to 42 days
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by vital signs in Part 3
Timeframe: Up to 42 days
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by ECG in Part 1 and Part 2
Timeframe: Up to 42 days
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by ECG in Part 3
Timeframe: Up to 42 days
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 1 and Part 2
Timeframe: Up to 42 days
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 3
Timeframe: Up to 42 days
Safety and tolerability of single IV dose of GSK2862277 as assessed by measurement of plasma cytokines in Part 1
Timeframe: Up to 42 days
Immunogenicity in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
Timeframe: Up to 60 days
Immunogenicity in subjects receiving repeat IV or IH dose of GSK2862277 in Part 3
Timeframe: Up to 60 days
Secondary outcomes:
Pharmacokinetic (PK) parameters in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
Timeframe: Up to 48 hours post dose
PK parameters in subjects receiving repeat IV dose of GSK2862277 in Part 3 Cohort 3a
Timeframe: Up to 48 hours post last dose
PK parameters in subjects receiving repeat IH dose of GSK2862277 in Part 3 Cohort 3b
Timeframe: Up to 48 hours post last dose
PK parameters in subjects receiving single IV dose of GSK2862277 in Part 1
Timeframe: Up to 48 hours post last dose
Pharmacodynamic and immune function biomarkers in serum of subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
Timeframe: Up to 48 hours post last dose
Pharmacodynamic and immune function biomarkers in serum of subjects receiving repeat IV or IH dose of GSK2862277in Part 3
Timeframe: Up to 48 hours post last dose
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
Timeframe: Up to 12 hours post dose
Composite of urine parameters in subjects receiving single IV 2 mg/kg dose of GSK2862277 in Part 2 in Cohort 2a
Timeframe: Up to 48 hours post dose
Interventions:
Drug: Single IV dose of GSK2862277
Drug: Matching placebo single dose IV infusion
Drug: Single IH dose of GSK2862277
Drug: Matching placebo single dose IH
Drug: Repeat IV dose of GSK2862277
Drug: Matching placebo repeat dose IV infusion
Drug: Repeat IH dose selected of GSK2862277 from Part 2
Drug: Matching placebo repeat dose IH
Enrollment:
54
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
J. C. Cordy, P. J. Morley, T. J. Wright, M. A. Birchler, A. P. Lewis, R. Emmins, Y. Z. Chen, W. M. Powley, P. J. Bareille, R. Wilson, J. Tonkyn, A. I. Bayliffe,A. L. Lazaar. Specificity of Human Anti-Variable Heavy (VH) Chain Autoantibodies and Impact on the Design and Clinical Testing of a VH Domain Antibody Antagonist of TNF-a Receptor 1.Clin Exp Immunol.2015;182(2):139-148.
Medical condition
Respiratory Disorders
Product
GSK2862277
Collaborators
Not applicable
Study date(s)
February 2013 to October 2013
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- 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.
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- 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.
Exclusion criteria:
- 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
Trial location(s)
Location
GSK Investigational Site
Harrow, Middlesex, United Kingdom, HA13UJ
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2013-25-10
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 116343 can be found on the GSK Clinical Study Register.
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