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GSK2018682 FTIH in Healthy Volunteers (P1A114070)

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
GSK2018682
Placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring GSK2018682, First Time in Human, Healthy Volunteer

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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. A subject with a clinical abnormality or laboratory parameters significantly 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. Subjects with lymphocyte counts outside the normal range should always be excluded from enrollment
  • BMI within the range 19 - 28 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
  • Subjects with a history of, or examination suspicious for, skin cancer(s) including melanoma, basal cell or squamous cell carcinoma.
  • Systolic blood pressure less than 95 mmHg or greater than 140 mmHg, or diastolic blood pressure less than or equal to 50 mmHg or greater than or equal to 95 mmHg.
  • Symptomatic reduction in blood pressure after orthostatic challenge.
  • Subjects with resting heart rate less than 45 beats per minute or greater than 90 beats per minute

Other criteria may apply as defined by the clinical protocol.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part A

Part B

Arm Description

Part A will be used to confirm the prediction of GSK2018682 PK, assess its effects on lymphocytes, and monitor its safety profile in a single cohort (Cohort 1). Cohort 1 will consist of 4 subjects and explore 4 doses of GSK2018682 in 4 study sessions. In each session, three subjects will receive GSK2018682 and one subject will receive placebo. Thus, when the cohort completes, each subject will receive placebo and 3 doses of GSK2018682.

Part B will explore doses to refine the dose-response curve of GSK2018682 on lymphocyte suppression, as allowed by stopping criteria, in 1 or 2 cohorts of up to 15 subjects (Cohort 2 and Cohort 3). In Part B, up to six single ascending doses of GSK2018682 and one dose of placebo will be investigated in up to 8 sessions.

Outcomes

Primary Outcome Measures

To investigate the safety and tolerability of single escalating oral doses of GSK2018682
Adverse event and safety lab monitoring
To investigate effects of GSK2018682 on heart rate and blood pressure
12 lead ECG and telemetry monitoring plus vital signs (systolic and diastolic blood blood pressures), heart rate, respiratory rate and temperature
To investigate the pharmacokinetics of single doses of GSK2018682
Peak blood concentration, time of peak blood concentration, oral clearance, half life and AUC
Evaluate the effect of single escalating oral doses of GSK2018682 on lymphocytes (totals plus subsets)
Reduction from baseline in lymphocyte counts obtained at different time points after dosing and at different dose levels

Secondary Outcome Measures

Full Information

First Posted
April 14, 2011
Last Updated
June 7, 2017
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT01387217
Brief Title
GSK2018682 FTIH in Healthy Volunteers
Acronym
P1A114070
Official Title
A Single-blind, Placebo-controlled, Two Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Doses of GSK2018682 in Healthy Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
May 21, 2010 (Actual)
Primary Completion Date
December 20, 2010 (Actual)
Study Completion Date
December 20, 2010 (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
This protocol describes the first administration of GSK2018682 to humans. The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of GSK2018682. The study will also provide preliminary evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on total lymphocyte counts.
Detailed Description
This protocol describes the first administration of GSK2018682 to humans. The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of GSK2018682. The study will also provide preliminary evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on total lymphocyte counts.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
GSK2018682, First Time in Human, Healthy Volunteer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A
Arm Type
Experimental
Arm Description
Part A will be used to confirm the prediction of GSK2018682 PK, assess its effects on lymphocytes, and monitor its safety profile in a single cohort (Cohort 1). Cohort 1 will consist of 4 subjects and explore 4 doses of GSK2018682 in 4 study sessions. In each session, three subjects will receive GSK2018682 and one subject will receive placebo. Thus, when the cohort completes, each subject will receive placebo and 3 doses of GSK2018682.
Arm Title
Part B
Arm Type
Experimental
Arm Description
Part B will explore doses to refine the dose-response curve of GSK2018682 on lymphocyte suppression, as allowed by stopping criteria, in 1 or 2 cohorts of up to 15 subjects (Cohort 2 and Cohort 3). In Part B, up to six single ascending doses of GSK2018682 and one dose of placebo will be investigated in up to 8 sessions.
Intervention Type
Drug
Intervention Name(s)
GSK2018682
Intervention Description
GSK2018682
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched Placebo
Primary Outcome Measure Information:
Title
To investigate the safety and tolerability of single escalating oral doses of GSK2018682
Description
Adverse event and safety lab 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 12 weeks
Title
To investigate effects of GSK2018682 on heart rate and blood pressure
Description
12 lead ECG and telemetry monitoring plus vital signs (systolic and diastolic blood blood pressures), heart rate, respiratory rate and temperature
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 12 weeks
Title
To investigate the pharmacokinetics of single doses of GSK2018682
Description
Peak blood concentration, time of peak blood concentration, oral clearance, half life and AUC
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 12 weeks
Title
Evaluate the effect of single escalating oral doses of GSK2018682 on lymphocytes (totals plus subsets)
Description
Reduction from baseline in lymphocyte counts obtained at different time points after dosing and at different dose levels
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 12 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. A subject with a clinical abnormality or laboratory parameters significantly 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. Subjects with lymphocyte counts outside the normal range should always be excluded from enrollment BMI within the range 19 - 28 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 Subjects with a history of, or examination suspicious for, skin cancer(s) including melanoma, basal cell or squamous cell carcinoma. Systolic blood pressure less than 95 mmHg or greater than 140 mmHg, or diastolic blood pressure less than or equal to 50 mmHg or greater than or equal to 95 mmHg. Symptomatic reduction in blood pressure after orthostatic challenge. Subjects with resting heart rate less than 45 beats per minute or greater than 90 beats per minute Other criteria may apply as defined by the clinical protocol.
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

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
114070
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
114070
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
114070
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
114070
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
114070
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
114070
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
114070
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register

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GSK2018682 FTIH in Healthy Volunteers

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