Clinical trial NCT02006537: A Study to Investigate the Safety and Pharmacokinetics of a Single Dose of GSK2256294 in Healthy Young Males and Elderly Subjects
Official title: A Study to Evaluate the Effect of Age, Food and Gender on Tolerability and Pharmacokinetics of GSK2256294 Following a Single Oral Administration in Healthy Fed and Fasted Elderly Subjects. This Study Will Also Evaluate the Biliary Metabolites in Healthy Young Males Following a Single Dose of GSK2256294
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: soluble epoxide hydrolase inhibitor
Entero-Test
pharmacokinetics
COPD
safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-12-10
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will investigate the safety and pharmacokinetics (PK) of a single dose of GSK2256294 in healthy young and elderly subjects to explore the effects of food, gender and age on drug exposure. The biliary metabolites in healthy young males will be investigated using the Entero-test after a single oral dose of GSK2256294. This study will be conducted in two cohorts (Cohort 1 and Cohort 2). Cohort 1 is open label in order to characterise the PK profile of GSK2256294 in healthy young males and also to investigate the biliary metabolites of GSK2256294. Cohort 2 uses a crossover design to allow comparison of the PK parameters of GSK2256294 between in the fed and fasted state within subject and also to compare the PK parameters of GSK2256294 between male and female subjects. A washout period of a minimum of 2 weeks has been chosen to allow and adequate washout of GSK2256294.


Eligibility criteria: Inclusion Criteria:

* Safety - All Cohorts
* 12 lead ECG without any clinically significant abnormality as judged by the Investigator, and ECGs QT duration corrected for heart rate by Fridericia's formula (QTcF) \<450 milliseconds (msec) determined by the average of triplicate ECGs.
* Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until 2 weeks post-last dose.
* Body weight \>=60 kilogram (kg) and body mass index (BMI) within the range 19 - 35 kg per meter square (kg/m\^2) (inclusive).
* Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin \<=1.5xUpper limit of normal \[ULN\] (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter outside the reference range for the population being studies may be included only of the Investigator agree that the finding is unlikely to introduce additional risk factors and will not interfere with study procedures. Consultation with the GSK Medical Monitor is required.
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* Safety - Cohort 2 Only
* A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy \[for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records\]; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 milli international units per milliliter (mIU/mL) and estradiol \<40 picogram per milliliter (pg/mL) (\<147 picomole per liter) is confirmatory\]. \[Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods listed in the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.\]
* Other - Cohort 1 Only.
* Cohort 1 only: Male aged between 18 and 45 years of age inclusive, at the time of signing the informed consent.

Cohort 1 only: BP \<=130/80.

* Other - Cohort 2 Only
* Cohort 2 only: Male and females (of non-child bearing potential) aged \>=60 years of age, at the time of signing the informed consent.
* Cohort 2 only: BP \<=160/100.

Exclusion Criteria:

* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

* History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
* A positive test for human immunodeficiency virus (HIV) antibody.
* A positive pre-study drug/alcohol screen.
* Subjects with a history of any type of malignancy with the exception of successfully treated squamous cell cancer of the skin.
* History of sensitivity to the study medication, or components thereof or a history of drug allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicated their participation.
* Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

Primary outcomes:
measure: Cohort 2: PK profiles of a single oral dose of GSK2256294
timeFrame: Pre-dose, 15 minutes (min), 30 min, 1 hour (h), 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1) and 24 h (Day 2), 48 h (Day 3) and 72 h (Day 4)
measure: Cohort 2: Electrocardiogram (ECG) as a measure of safety and tolerability
timeFrame: Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
measure: Cohort 2: Adverse events (AEs ) as a measure of safety and tolerability
timeFrame: From the start of study treatment and until approximately 2 weeks after the final dose
measure: Cohort 2: Vital signs as a measure of safety and tolerability
timeFrame: Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
measure: Cohort 2: Laboratory assessments as a measure of safety and tolerability
timeFrame: Screening and follow-up. In addition, clinical chemistry will also be done at 12 h (Day 1) and 24 h (Day 2)
Secondary outcomes:
measure: Cohort 1: Biliary metabolite profile of GSK2256294
timeFrame: Until 7 hours post-dose on Day 1
measure: Cohort 1: AEs as a measure of safety and tolerability
timeFrame: From the start of study treatment and until approximately 2 weeks after the final dose
measure: Cohort 1: ECG as a measure of safety and tolerability
timeFrame: Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
measure: Cohort 1: Vital signs as a measure of safety and tolerability
timeFrame: Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
measure: Cohort 1: Laboratory assessments as a measure of safety and tolerability
timeFrame: Screening and follow-up
measure: Cohort 1 and Cohort 2: AUC, Cmax, t1/2,and Tmax of GSK2256294
timeFrame: Cohort 1: Pre-dose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 7 h, 12 h and 24 h, 48 h, and 72 h; Cohort 2: Pre-dose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 24 h, 48 h and 72 h
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Lazaar AL, Yang L, Boardley RL, Goyal NS, Robertson J, Baldwin SJ, Newby DE, Wilkinson IB, Tal-Singer R, Mayer RJ, Cheriyan J. Pharmacokinetics, pharmacodynamics and adverse event profile of GSK2256294, a novel soluble epoxide hydrolase inhibitor. Br J Clin Pharmacol. 2016 May;81(5):971-9. doi: 10.1111/bcp.12855. Epub 2016 Jan 17.