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

NCT01687309 | Completed Phase 1

• 1 other identifier: 116439
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

A study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and repeat doses of 800 mg GSK2586184 in healthy subjects.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (6)

• Adverse event reporting

  Change in health of subjects

  Day 1 through to within 7-10 days after the last dose

• Change from baseline in clinical chemistry, hematology, urinalysis

  Change in clinical chemistry, hematology and urinalysis from baseline

  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

  Change in blood pressure, heart rate and body temperature outside normal range

  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

  Change in ECG parameters outside normal range

  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

  Change in plasma concentrations of GSK2586184

  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

  Change in 24h urine creatinine, albumin and PCR values outside normal range

  Cohort B repeat dose: D-1, D10 and within 7-10 days post last dose

Secondary Outcomes (6)

• mRNA expression of IFNa and JAK pathway genes

  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

  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

  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

  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

  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

Study Arms (4)

Cohort A fed session

OTHER

GSK2586184 800mg single dose with food

Other: GSK2586184 single dose taken with food

Cohort A fasted session

OTHER

GSK2586184 single dose without food

Other: GSK2586184 single dose taken without food

Cohort B active study medication

ACTIVE COMPARATOR

GSK2586184 800mg single and twice daily dose for 13 days

Drug: GSK2586184 800mg single and repeat dose

Cohort B placebo

PLACEBO COMPARATOR

Placebo-to-match single and twice daily dose for 13 days

Drug: Placebo-to-match GSK2586184

Interventions

GSK2586184 800mg single and repeat dose DRUG

GSK2586184 800mg single dose and then twice daily dosing for 13 days

Cohort B active study medication

Placebo-to-match GSK2586184 DRUG

Placebo-to-match GSK2586184

Cohort B placebo

GSK2586184 single dose taken with food OTHER

GSK2586184 single dose taken with FDA approved high fat, high calorie breakfast

Cohort A fed session

GSK2586184 single dose taken without food OTHER

GSK2586184 single dose taken in a fasted state

Cohort A fasted session

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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
• 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

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 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)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Antwerp, 2060, Belgium

Location

Related Links

• Results for study 116439 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

GSK2586184; Single Person; Food

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2012
• First Posted: September 18, 2012
• Study Start: April 30, 2012
• Primary Completion: July 31, 2012
• Study Completion: July 31, 2012
• Last Updated: May 25, 2018

Record last verified: 2018-05

Locations

BE (1)