Assessment of Repeat Ascending Doses of GSK2018682 in Healthy Volunteers

NCT01431937 | Completed Phase 1

• 1 other identifier: 114347
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

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).

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Pharmacodynamics; Pharmacokinetics

Outcome Measures

Primary Outcomes (8)

• 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

  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

• 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

  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

• To investigate effects of repeat oral doses of GSK2018682 on lung function in healthy volunteers

  FEV1 obtained via spirometry

  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

• 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

  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

• To characterize the metabolism of GSK2018682

  GSK2018682 bile metabolites, GSK2018682 whole blood metabolites

  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

• 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)

  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

• 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

  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

• 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)

  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

Study Arms (2)

GSK2018682

ACTIVE COMPARATOR

Active Drug

Drug: GSK2018682

Placebo Control

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

GSK2018682 DRUG

Active Drug

GSK2018682

Placebo DRUG

Placebo

Placebo Control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

GSK Investigational Site

Adelaide, South Australia, 5000, Australia

Location

GSK Investigational Site

Nedlands, Western Australia, 6009, Australia

Location

Related Links

• Results for study 114347 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

GSK2018682

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2011
• First Posted: September 12, 2011
• Study Start: October 10, 2010
• Primary Completion: March 29, 2011
• Study Completion: March 29, 2011
• Last Updated: July 7, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

AU (3)