Assessment of Repeat Ascending Doses of GSK2018682 in Healthy Volunteers (P1A114347)
Primary Purpose
Multiple Sclerosis, Relapsing-Remitting
Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
GSK2018682
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting focused on measuring Pharmacodynamics, Pharmacokinetics
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
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
GSK2018682
Placebo Control
Arm Description
Active Drug
Placebo
Outcomes
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)
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
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
FEV1 obtained via spirometry
To investigate the pharmacokinetics of repeat oral doses of GSK2018682 in healthy volunteers
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
GSK2018682 bile metabolites, GSK2018682 whole blood metabolites
Evaluate the effect of repeat oral doses of GSK2018682 on lymphocytes in healthy volunteers
% 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
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
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)
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01431937
Brief Title
Assessment of Repeat Ascending Doses of GSK2018682 in Healthy Volunteers
Acronym
P1A114347
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
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
October 10, 2010 (Actual)
Primary Completion Date
March 29, 2011 (Actual)
Study Completion Date
March 29, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-Remitting
Keywords
Pharmacodynamics, Pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GSK2018682
Arm Type
Active Comparator
Arm Description
Active Drug
Arm Title
Placebo Control
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
GSK2018682
Intervention Description
Active Drug
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
To investigate the safety and tolerability of repeat oral doses of GSK2018682 in healthy volunteers (males and females of non-childbearing potential)
Description
Adverse event monitoring, Laboratory parameters (haematology, clinical chemistry, urinalysis), Ophthalmic examination
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
Title
To investigate effects of repeat oral doses of GSK2018682 on heart rate and blood pressure in healthy volunteers
Description
12-lead ECG, Telemetry ECG, Holter ECG, Vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, body temperature), Ambulatory blood pressure monitoring
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
Title
To investigate effects of repeat oral doses of GSK2018682 on lung function in healthy volunteers
Description
FEV1 obtained via spirometry
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
Title
To investigate the pharmacokinetics of repeat oral doses of GSK2018682 in healthy volunteers
Description
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
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
Title
To characterize the metabolism of GSK2018682
Description
GSK2018682 bile metabolites, GSK2018682 whole blood metabolites
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
Title
Evaluate the effect of repeat oral doses of GSK2018682 on lymphocytes in healthy volunteers
Description
% 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)
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
Title
To explore the PK/PD relationship between blood concentrations and changes in vital signs and ECG parameters
Description
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
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
Title
To explore the PK/PD relationship between blood concentrations of GSK2018682 and reduction in lymphocyte counts
Description
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)
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
GSK Investigational Site
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
GSK Investigational Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
114347
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
114347
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
114347
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
114347
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
114347
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
114347
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
114347
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Assessment of Repeat Ascending Doses of GSK2018682 in Healthy Volunteers
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