A study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat doses of GSK2586184 and the effect of food and genderJAK116439
Trial overview
Adverse event reporting
Timeframe: Day 1 through to within 7-10 days after the last dose
Change from baseline in clinical chemistry, hematology, urinalysis
Timeframe: Cohort A: D-1, predose (each session), D2 (each session) and 7-10 days after the last dose. Cohort B single dose session: D-3, predose, D2. Cohort B repeat dose session: D1, D2, D5, D10, D11, D14 and within 7-10 days after last dose
Change from baseline in vital signs parameters
Timeframe: Cohort A: Predose, 2h post dose, D2, within 7-10 days from last dose. Cohort B single dose session: D-3, predose, 2h post-dose, D2. Cohort B repeat dose session: predose on D1, D2, D5, D10, 2h post-dose on D1 and D10, D14, within 7-10 days post last dose
Change from baseline in ECG parameters
Timeframe: Cohort A: Predose, 2h post dose, D2 and within 7-10 days of last dose. Cohort B single dose session: D-3, pre-dose, 2h post-dose and D2. Cohort B repeat dose session: pre-dose, D2, D5, D10, 2h post-dose on D1, D10, D14 and within 7-10 days from last dose
Plasma concentrations of GSK2586184
Timeframe: Cohort A: 0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48h post-dose. Cohort B single dose session:0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48h post-dose. Cohort B repeat dose session: D1 and D10 (predose, 0.25, 0.5, 1, 2, 4, 8 and 12h post-dose), D2, D3, D4, D5, and D11
Change from baseline for 24h urine albumin, creatinine and PCR
Timeframe: Cohort B repeat dose: D-1, D10 and within 7-10 days post last dose
mRNA expression of IFNa and JAK pathway genes
Timeframe: Cohort B repeat dose: Predose, 1, 2, 4, 8 and 12h on D1 and D10. Predose, 1, 2, 4, 8, 12 and 24h post-dose on D11
Vital signs as a pharmacodynamic endpoint
Timeframe: Cohort B repeat dose: Predose, 4, 8, 12, 24, 28, 32, 48, 72, 100 and 120h post dose on D11
Plasma levels of Neopterin and B2-microglobulin
Timeframe: Cohort B repeat dose: Predose, 4, 8, 12, 24, 28, 32, 48, 72, 100 and 120h post dose on D11
Glomerular Filtration Measurement using Cr-51 EDTA
Timeframe: Cohort B: 2h and 4h post Cr-51 EDTA injection on D-2 of single dose session, D8 of repeat dose session and within 7-10 days post last dose
Duodenal concentrations of GSK2586184 and its metabolites and derived pharmacokinetic parameters
Timeframe: Cohort A: D-1 to D1 predose and 2.5h post-dose to 6.5h post-dose. Cohort B single dose: D-1 to D1 predose and 2.5h post-dose to 6.5h post-dose
Urine concentrations of GSK2586184 and its metabolites and derived pharmacokinetic parameters
Timeframe: Cohort A: D1 predose and for 24 hr post-dose.Cohort B single dose: D1 predose and for 24h post-dose
Participation criteria
- Healthy as determined by a responsible and experienced physician, based on a
- medical evaluation including medical history, physical examination, laboratory tests
- 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)
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring
- Cohort A: A female subject of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea
- Cohort B: Male subjects with female partners of child-bearing potential must agree to contraception method mandated by protocol
- Cohort A: Subjects between 18 and 65 years of age inclusive, at the time of signing the informed consent
- Cohort B: Subjects between 18 and 50 years of age inclusive, at the time of signing the informed consent
- Normal creatinine clearance values at screening
- ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- Single QTcF < 480 msec
- BMI within the range 18 – 30.0 kg/m2 (inclusive)
- Subjects must be non-smokers and must not use any nicotine-containing products. A non-smoker is defined as an individual who has abstained from smoking for at least 1 year prior to screening
- 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 sensitivity to any of the study medications, Intron A or other recombinant interferons, 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
- 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 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)
- The subject is unwilling to abstain from alcohol consumption from 48 hr prior to dosing until discharge from the clinic, and for 24 hr prior to all other out-patient clinic visits
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day
- Unable to refrain from the 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 malignancy, except for adequately treated non-invasive cancer of the skin (basal or squamous cell) or cervical carcinoma in situ (>2 yrs prior to dosing)
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
- Subjects with a history of or a current thyroid disease or epilepsy
- Subjects exposed to radiation in the 6 months, (except for X-ray/CT examinations of the extremities) prior to the first GFR assessment (Day -2) (cohort B only)
Trial location(s)
Study documents
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.