A Two-part, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamicsof Single and Repeat Doses of Intravenously Infused GSK1995057 in Healthy Subjects.
Overview
- Phase
- Phase 1
- Intervention
- GSK1995057 single dose
- Conditions
- Respiratory Disorders
- Sponsor
- GlaxoSmithKline
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Occurance of adverse events.
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The main purpose of the study is to see how safe GSK1995057 is and how well it is tolerated after dosing. The study will also investigate how GSK1995057 is taken up, metabolised (chemically broken down), distributed through the body and excreted, and what some of the effects of the study drug are.
Detailed Description
This study will be the first investigation of GSK1995057 in humans and is primarily designed to investigate safety and tolerability of single and repeat intravenously infused doses. The study will enrol healthy male subjects and healthy female subjects of non-child bearing potential and will also investigate immunogenicity, GSK1995057 distribution (pharmacokinetics), and potential impact on indicators of host immunity and normal immunological function. Safety, tolerability, immunogenicity, pharmacokinetic and pharmacodynamic data from this trial may facilitate further clinical investigations in healthy subjects dosed with GSK1995057 via the inhaled route, and ultimately clinical trials in patients with acute lung injury.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy as determined by a responsible and experienced physician.
- •Male or female between 18 and 55 years of age inclusive
- •A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy or bilateral oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea and elevated FSH as per the local laboratory guidelines.
- •Normal creatinine clearance values at screening
- •Male subjects must agree to use one of the study specific contraception methods
- •Body weight ≥ 50 kg and BMI within the range 19 - 29.9 kg/m2 (inclusive).
- •Normal lung function at screening.
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- •Available to complete all study assessments.
- •Able to read, comprehend and write English at a sufficient level to complete study elated materials.
Exclusion Criteria
- •A history of Hepatitis B, Hepatitis C or HIV infection and/or a positive pre-study HIV, 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 known Gilbert's syndrome or asymptomatic gallstones).
- •A positive pre-study drug/alcohol screen.
- •Evidence of previous or active mycobacterium tuberculosis complex infection
- •Recent history of and/or a positive test for Toxoplasma consistent with active oxoplasmosis infection.
- •A positive test for influenza A/B taken within 7 days before dosing.
- •Current evidence or history of an influenza-like illness.
- •Corrected QT interval (QTcF) \>450msec from ECG readings.
- •History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 g of alcohol and the following can be used as a guide: a half-pint (\~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
- •The subject is unwilling to abstain from alcohol consumption from 24 hr prior to dosing until discharge from the clinic, and for 24 hr prior to all other out-patient clinic visits.
Arms & Interventions
GSK1995057
Single intravenous dose
Intervention: GSK1995057 single dose
Placebo
Single intravenous dose
Intervention: Placebo
Outcomes
Primary Outcomes
Occurance of adverse events.
Time Frame: From start of screening until 84 days after completion of single dose (Part A subjects) or first dose (Part B subjects).
Number and type of adverse events recorded during study.
Change from baseline in blood pressure.
Time Frame: From start of screening until 28 days after completion of single or repeat dosing.
Systolic and diastolic blood pressure values before and after dosing completion.
Change from baseline in heart rate.
Time Frame: From start of screening until 28 days after completion of single or repeat dosing.
Heart rate before and after dosing completion.
Change from baseline in respiration rate.
Time Frame: From start of screening until 28 days after completion of single or repeat dosing.
Respiration rate before and after dosing completion.
Change from baseline in body temperature.
Time Frame: From start of screening until 28 days after completion of single or repeat dosing.
Body temperature before and after dosing completion.
Change from baseline in heart function.
Time Frame: From start of screening until 28 days after completion of single or repeat dosing.
12-lead ECG recording.
Change from baseline in heart function
Time Frame: From 1 hour before dosing to 12 hours after dosing starts for each dose.
Lead II cardiac telemetry.
Change from baseline in lung function.
Time Frame: From start of screening until 28 days after completion of single or repeat dosing.
FEV1 and FVC measurements.
Change from baseline in laboratory safety data.
Time Frame: From start of screening until 28 days after completion of single or repeat dosing.
Clinical chemistry, haematology and routine urinalysis.
Secondary Outcomes
- Plasma pharmacokinetics of GSK1995057(From the first day of dosing until 48 hours after the completion of dosing.)
- Urine pharmacokinetics of GSK1995057(From 1 hour before the only dose until 48 hours after the dose.)
- Bronchoalveolar lavage fluid (BALF) (saline flushed into and then collected from a lung) pharmacokinetics.(At 2 hrs after the completion of the only dose.)
- Effects of GSK1995057 on host immunity and immunological function(At 2 hrs after the completion of the only dose.)
- Effect of GSK1995057 on host immunity and immunological function(From the day before dosing starts to 28 days after dosing completion.)
- Immunogenic effect of GSK1995057(From the start of screening (cohorts 1-4 only) or from the day before the start of dosing until 84 days after the completion of single or repeat dosing.)