A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Doses of GSK2586184 and the Effect of Food and Gender

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01687309
• Date of registration: 10/05/2012
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Doses of GSK2586184 and the Effect of Food and Gender JAK116439
• Scientific title: A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2586184 Following a Single Doseof 800mg and Repeat Oral Tablet Doses of 800mg b.d and the Effect of Food and Gender on the Pharmacokinetics of oralGSK2586184 in Healthy Subjects
• Date of first enrolment: April 30, 2012
• Target sample size: 19
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01687309
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

Belgium

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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

- 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

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 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)



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Other: GSK2586184 single dose taken without food

Drug: Placebo-to-match GSK2586184

Drug: GSK2586184 800mg single and repeat dose

Other: GSK2586184 single dose taken with food

Primary Outcome(s)

Plasma concentrations of GSK2586184 [Time Frame: 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 in clinical chemistry, hematology, urinalysis [Time Frame: 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 ECG parameters [Time Frame: 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]

Change from baseline in vital signs parameters [Time Frame: 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]

Adverse event reporting [Time Frame: Day 1 through to within 7-10 days after the last dose]

Change from baseline for 24h urine albumin, creatinine and PCR [Time Frame: Cohort B repeat dose: D-1, D10 and within 7-10 days post last dose]

Secondary Outcome(s)

Glomerular Filtration Measurement using Cr-51 EDTA [Time Frame: 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]

mRNA expression of IFNa and JAK pathway genes [Time Frame: 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]

Duodenal concentrations of GSK2586184 and its metabolites and derived pharmacokinetic parameters [Time Frame: 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]

Vital signs as a pharmacodynamic endpoint [Time Frame: Cohort B repeat dose: Predose, 4, 8, 12, 24, 28, 32, 48, 72, 100 and 120h post dose on D11]

Urine concentrations of GSK2586184 and its metabolites and derived pharmacokinetic parameters [Time Frame: Cohort A: D1 predose and for 24 hr post-dose.Cohort B single dose: D1 predose and for 24h post-dose]

Plasma levels of Neopterin and B2-microglobulin [Time Frame: Cohort B repeat dose: Predose, 4, 8, 12, 24, 28, 32, 48, 72, 100 and 120h post dose on D11]

Secondary ID(s)

116439

Source(s) of Monetary Support

Please refer to primary and secondary sponsors