GSK2018682 FTIH in Healthy Volunteers
- Registration Number
- NCT01387217
- Lead Sponsor
- GlaxoSmithKline
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 27
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part A Placebo 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 A GSK2018682 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 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. Part B Placebo 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.
- Primary Outcome Measures
Name Time Method To investigate the pharmacokinetics of single doses of GSK2018682 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 Peak blood concentration, time of peak blood concentration, oral clearance, half life and AUC
To investigate the safety and tolerability of single escalating oral doses of GSK2018682 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 Adverse event and safety lab monitoring
To investigate effects of GSK2018682 on heart rate and blood pressure 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 12 lead ECG and telemetry monitoring plus vital signs (systolic and diastolic blood blood pressures), heart rate, respiratory rate and temperature
Evaluate the effect of single escalating oral doses of GSK2018682 on lymphocytes (totals plus subsets) 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 Reduction from baseline in lymphocyte counts obtained at different time points after dosing and at different dose levels
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
GSK Investigational Site
🇦🇺Adelaide, South Australia, Australia