A Study to Investigate the Safety Tolerability Pharmacokinetics, and Pharmacodynamics of Inhaled and Intravenous GSK2862277 in Healthy Volunteers

Respiratory Disorders Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01818024
• Other study ID #: 116343
• Status: Completed
• Phase: Phase 1
• First received: February 14, 2013
• Last updated: May 12, 2017
• Start date: February 22, 2013
• Est. completion date: October 25, 2013

Study information

• Verified date: May 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: October 25, 2013
• Est. primary completion date: October 25, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Respiration Disorders
• Respiratory Disorders
• Respiratory Tract Diseases

Intervention

Drug:
• Single IV dose of GSK2862277
GSK2862277 solution available in a 40 mg vial for IV administration.
• Matching placebo single dose IV infusion
Matching placebo solution available for IV administration.
• Single IH dose of GSK2862277
GSK2862277 nebulised solution available in a 40 mg vial for IH administration.
• Matching placebo single dose IH
Matching placebo nebulised solution available for IH administration.
• Repeat IV dose of GSK2862277
GSK2862277 solution available in a 40 mg vial for IV administration.
• Matching placebo repeat dose IV infusion
Matching placebo solution available for IV administration.
• Repeat IH dose selected of GSK2862277 from Part 2
GSK2862277 nebulised solution available in a 40 mg vial for IH administration.
• Matching placebo repeat dose IH
Matching placebo nebulised solution available for IH administration.

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Harrow	Middlesex

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Safety and tolerability parameters will include recording of adverse events (AEs), throughout the study.	Up to 42 days
Primary	Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by number of subjects with AEs in Part 3	Safety and tolerability parameters will include recording of AEs, throughout the study.	Up to 42 days
Primary	Safety and tolerability of single IV or IH dose of GSK2862277 assessed by laboratory tests in Part 1 and Part 2	Laboratory tests will include haemogram, clinical chemistry, urine examination.	Up to 42 days
Primary	Safety and tolerability of repeat IV or IH dose of GSK2862277 as assessed by laboratory tests in Part 3	Laboratory tests will include haemogram, clinical chemistry, urine examination.	Up to 42 days
Primary	Safety and tolerability of single IV or IH dose of GSK2862277 assessed by vital signs in Part 1 and Part 2	Vital signs will include blood pressure (BP), heart rate respiration rate and body temperature.	Up to 42 days
Primary	Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by vital signs in Part 3	Vital signs will include BP, heart rate respiration rate and body temperature.	Up to 42 days
Primary	Safety and tolerability of single IV or IH dose of GSK2862277 assessed by ECG in Part 1 and Part 2	Safety data will include electrocardiogram (ECG) readings obtained at each timepoint during the study.	Up to 42 days
Primary	Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by ECG in Part 3	Safety data will include ECG readings obtained at each timepoint during the study.	Up to 42 days
Primary	Safety and tolerability of single IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 1 and Part 2	Spirometry monitoring will include forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).	Up to 42 days
Primary	Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 3	Spirometry monitoring will include FEV1 and FVC.	Up to 42 days
Primary	Safety and tolerability of single IV dose of GSK2862277 as assessed by measurement of plasma cytokines in Part 1	Blood samples will be collected for assessment of plasma cytokines.	Up to 42 days
Primary	Immunogenicity in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2	Presence of anti GSK2862277 binding antibodies will be evaluated.	Up to 60 days
Primary	Immunogenicity in subjects receiving repeat IV or IH dose of GSK2862277 in Part 3	Presence of anti GSK2862277 binding antibodies will be evaluated.	Up to 60 days
Secondary	Pharmacokinetic (PK) parameters in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2	The blood samples will be collected for plasma concentrations of GSK2862277.	Up to 48 hours post dose
Secondary	PK parameters in subjects receiving repeat IV dose of GSK2862277 in Part 3 Cohort 3a	The blood samples will be collected for plasma concentrations of GSK2862277.	Up to 48 hours post last dose
Secondary	PK parameters in subjects receiving repeat IH dose of GSK2862277 in Part 3 Cohort 3b	The blood samples will be collected for plasma concentrations of GSK2862277	Up to 48 hours post last dose
Secondary	PK parameters in subjects receiving single IV dose of GSK2862277 in Part 1	The PK parameters will be compared with historic GSK1995057 PK data in Part 1	Up to 48 hours post last dose
Secondary	Pharmacodynamic and immune function biomarkers in serum of subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2	The pharmacodynamic and immune function biomarkers in serum.	Up to 48 hours post last dose
Secondary	Pharmacodynamic and immune function biomarkers in serum of subjects receiving repeat IV or IH dose of GSK2862277in Part 3	The pharmacodynamic and immune function biomarkers in serum.	Up to 48 hours post last dose
Secondary	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	IL-8 expression in ex vivo whole blood essay (WBA).	Up to 12 hours post dose
Secondary	Composite of urine parameters in subjects receiving single IV 2 mg/kg dose of GSK2862277 in Part 2 in Cohort 2a	The urine samples will be collected for urine concentrations of GSK2862277.	Up to 48 hours post dose

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
•   Results for study 116343 can be found on the GSK Clinical Study Register.