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

NCT ID: NCT01687309

Last Updated: 2018-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2012-07-31

Brief Summary

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

Detailed Description

This is a study in healthy volunteers to investigate the safety, tolerability, pharmacokinetics (the body's effect on the drug) and pharmacodynamics (the drug's effect on the body) of single and repeat doses of 800 mg GSK2586184. The effect of food and gender on pharmacokinetics will also be investigated following single dosing.

The study is made up of 2 groups of healthy subjects. The first group consists of 6 female subjects who will receive a single dose of 800mg GSK2586184 (study medication) during 2 seperate sessions. One session will involve the female subjects taking the study medication with food and the other session will involve study medication being taken without food. The safety and tolerability of the study medication in female subjects and the effect of food on the pharmacokinetics of the study medication will be investigated.

The second group will consist of 12 healthy male subjects participating in 2 sessions. 8 subjects will receive study medication and 4 will receive placebo (dummy medication) during the course of the study. Neither they or their study doctor will know which one they are given. Each male subject will receive a single dose of study medication or placebo followed by 13 days of twice daily dosing of study medication or placebo. Each dose will be taken with food.The single dose results from this group of subjects will be compared to the female group to investigate the effect of gender on pharmacokinetics. The safety and pharmacokinetics of repeat dosing will be investigated. The effect of repeat dosing on kidney function and the immune system will also be investigated.

The study will take place in the SGS Clinical Pharmacology Unit in Antwerp, Belgium. A pharmaceutical company, GlaxoSmithKline, is funding the study.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort A fed session

GSK2586184 800mg single dose with food

Group Type: OTHER

GSK2586184 single dose taken with food

Intervention Type: OTHER

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

Cohort A fasted session

GSK2586184 single dose without food

Group Type: OTHER

GSK2586184 single dose taken without food

Intervention Type: OTHER

GSK2586184 single dose taken in a fasted state

Cohort B active study medication

GSK2586184 800mg single and twice daily dose for 13 days

Group Type: ACTIVE_COMPARATOR

GSK2586184 800mg single and repeat dose

Intervention Type: DRUG

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

Cohort B placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo-to-match GSK2586184

Intervention Type: DRUG

Placebo-to-match GSK2586184

Interventions

GSK2586184 800mg single and repeat dose

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

Intervention Type: DRUG

Placebo-to-match GSK2586184

Placebo-to-match GSK2586184

Intervention Type: DRUG

GSK2586184 single dose taken with food

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

Intervention Type: OTHER

GSK2586184 single dose taken without food

GSK2586184 single dose taken in a fasted state

Intervention Type: OTHER

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Antwerp, , Belgium

Countries

Belgium

Other Identifiers

116439

Identifier Type: -

Identifier Source: org_study_id