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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Respiratory Disorders

Treatments: Drug: Single IV dose of GSK2862277; Drug: Matching placebo repeat dose IH; Drug: Repeat IH dose selected of GSK2862277 from Part 2; Drug: Matching placebo single dose IH; Drug: Repeat IV dose of GSK2862277; Drug: Matching placebo repeat dose IV infusion; Drug: Matching placebo single dose IV infusion; Drug: Single IH dose of GSK2862277

Study type: Interventional

Funder types: Industry

Identifiers

NCT01818024

116343

Details and patient eligibility

About

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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Single Blind

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54 participants in 11 patient groups

Part 1: Cohort 1a

Experimental group

Description:

Single IV dose of GSK2862277 as a continuous infusion over 2 hours.

Treatment:

Drug: Single IV dose of GSK2862277

Part 1: Cohort 1b

Experimental group

Description:

Single IV dose of GSK2862277 as a continuous infusion over 3 hours.

Treatment:

Drug: Single IV dose of GSK2862277

Part 1: Cohort 1c

Experimental group

Description:

Single IV dose of GSK2862277 as a continuous infusion over 3 hours.

Treatment:

Drug: Single IV dose of GSK2862277

Part 2: Cohort 2a GSK2862277

Experimental group

Description:

Single IV dose of GSK2862277 as a continuous infusion over 1 hour.

Treatment:

Drug: Single IV dose of GSK2862277

Part 2: Cohort 2a Placebo

Experimental group

Description:

Matching placebo will be administered as a continuous IV infusion over 1 hour.

Treatment:

Drug: Matching placebo single dose IV infusion

Part 2: Cohort 2b GSK2862277

Experimental group

Description:

Single IH dose of GSK2862277.

Treatment:

Drug: Single IH dose of GSK2862277

Part 2: Cohort 2b Placebo

Experimental group

Description:

Matching placebo will be administered.

Treatment:

Drug: Matching placebo single dose IH

Part 3: Cohort 3a GSK2862277

Experimental group

Description:

IV dose of GSK2862277 (decided from Part 2) as a continuous infusion over 1 hour for daily 5 days.

Treatment:

Drug: Repeat IV dose of GSK2862277

Part 3: Cohort 3a Placebo

Experimental group

Description:

Matching placebo will be administered as IV infusion over 1 hour daily for 5 days.

Treatment:

Drug: Matching placebo repeat dose IV infusion

Part 3: Cohort 3b GSK2862277

Experimental group

Description:

Repeat IH dose of GSK2862277 (decided from Part 2) daily for 5 days.

Treatment:

Drug: Repeat IH dose selected of GSK2862277 from Part 2

Part 3: Cohort 3b Placebo

Experimental group

Description:

Matching placebo will be administered as IH daily for 5 days.

Treatment:

Drug: Matching placebo repeat dose IH