Assessment of Repeat Ascending Doses of GSK2018682 in Healthy Volunteers - Full Text View

Purpose

The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat ascending doses of GSK2018682. The study will also provide further evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on Absolute Lymphocyte Counts (ALC).

Condition	Intervention	Phase
Multiple Sclerosis, Relapsing-Remitting	Drug: GSK2018682 Drug: Placebo	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Crossover Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	A Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Repeat Ascending Doses of GSK2018682 (S1P1 Agonist) in Healthy Volunteers

Resource links provided by NLM:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

To investigate the safety and tolerability of repeat oral doses of GSK2018682 in healthy volunteers (males and females of non-childbearing potential) [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks ] [ Designated as safety issue: No ]
Adverse event monitoring, Laboratory parameters (haematology, clinical chemistry, urinalysis), Ophthalmic examination
To investigate effects of repeat oral doses of GSK2018682 on heart rate and blood pressure in healthy volunteers [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks ] [ Designated as safety issue: No ]
12-lead ECG, Telemetry ECG, Holter ECG, Vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, body temperature), Ambulatory blood pressure monitoring
To investigate effects of repeat oral doses of GSK2018682 on lung function in healthy volunteers [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks ] [ Designated as safety issue: No ]
FEV1 obtained via spirometry
To investigate the pharmacokinetics of repeat oral doses of GSK2018682 in healthy volunteers [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks ] [ Designated as safety issue: No ]
Peak blood concentration, Time of peak blood concentration, Area under the blood concentration-time curve over the 24-hour dose interval and area under the blood concentration-time curve from time-zero extrapolated to infinite time, Accumulation ratio, Terminal half-life, Apparent oral clearance, Through concentration
To characterize the metabolism of GSK2018682 [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks ] [ Designated as safety issue: No ]
GSK2018682 bile metabolites, GSK2018682 whole blood metabolites
Evaluate the effect of repeat oral doses of GSK2018682 on lymphocytes in healthy volunteers [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks ] [ Designated as safety issue: No ]
% Change from baseline in absolute lymphocyte counts (ALC), % Change from baseline in subsets CD3+ [CD4+ and CD8+], CD19+, CD16+/CD56+ counts, % Change from baseline in further defined functional T cell subsets (naïve, central memory, effector memory and regulatory T cells)
To explore the PK/PD relationship between blood concentrations and changes in vital signs and ECG parameters [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks ] [ Designated as safety issue: No ]
PK/PD model with parameters of the models will be determined that best describe the relationship between blood concentrations of GSK2018682 and vital signs and ECG parameters
To explore the PK/PD relationship between blood concentrations of GSK2018682 and reduction in lymphocyte counts [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks ] [ Designated as safety issue: No ]
PK/PD model with parameters of the models will be determined that best describe the relationship between blood concentrations of GSK2018682 and reduction ALC and subset counts CD3+ [CD4+ and CD8+], CD19+, CD16+/CD56+ and further defined functional T cell subsets (naïve, central memory, effector memory and regulatory T cells)

Enrollment:	40
Study Start Date:	October 2010
Study Completion Date:	March 2011
Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: GSK2018682 Active Drug	Drug: GSK2018682 Active Drug
Placebo Comparator: Placebo Control Placebo	Drug: Placebo Placebo

Detailed Description:

The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat ascending doses of GSK2018682. The study will also provide further evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on Absolute Lymphocyte Counts (ALC).

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
Females must be of non-childbearing potential.
BMI within the range 19 - 29 kg/m2 (inclusive).

Exclusion Criteria:

A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
A positive pre-study drug/alcohol screen.
A positive test for HIV antibody.
History of regular alcohol consumption within 6 months of the study.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
Were participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
Unwillingness or inability to follow the procedures outlined in the protocol.
Other exclusion criteria to be detailed at the time of physical screening by the Investigator

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01431937

Locations

Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Australia, South Australia
GSK Investigational Site
Adelaide, South Australia, Australia, 5000
Australia, Western Australia
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT01431937 History of Changes
Other Study ID Numbers:	114347
Study First Received:	August 11, 2011
Last Updated:	February 2, 2012
Health Authority:	Australia: Human Research Ethics Committee Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:

Pharmacodynamics
Pharmacokinetics

Additional relevant MeSH terms:

Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System

Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 23, 2013

Assessment of Repeat Ascending Doses of GSK2018682 in Healthy Volunteers (P1A114347)