Clinical trial NCT01431937: Assessment of Repeat Ascending Doses of GSK2018682 in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: Pharmacodynamics
Pharmacokinetics
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-09-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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).

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 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

Primary outcomes:
measure: To investigate the safety and tolerability of repeat oral doses of GSK2018682 in healthy volunteers (males and females of non-childbearing potential)
timeFrame: 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
measure: To investigate effects of repeat oral doses of GSK2018682 on heart rate and blood pressure in healthy volunteers
timeFrame: 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
measure: To investigate effects of repeat oral doses of GSK2018682 on lung function in healthy volunteers
timeFrame: 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
measure: To investigate the pharmacokinetics of repeat oral doses of GSK2018682 in healthy volunteers
timeFrame: 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
measure: To characterize the metabolism of GSK2018682
timeFrame: 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
measure: Evaluate the effect of repeat oral doses of GSK2018682 on lymphocytes in healthy volunteers
timeFrame: 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
measure: To explore the PK/PD relationship between blood concentrations and changes in vital signs and ECG parameters
timeFrame: 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
measure: To explore the PK/PD relationship between blood concentrations of GSK2018682 and reduction in lymphocyte counts
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Adelaide
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: