Clinical trial NCT00359177: Observational Study Evaluating The Processing Or Breakdown Of GW679769 In Subjects With Hepatic Impairment
Official title: An Open-Label, Non-Randomized, Pharmacokinetic and Safety Study of Multiple Oral Doses of GW679769 in Subjects With Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Vomiting
Keywords: emesis liver problems hepatic impairment GW679769
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-08-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate how subjects with mild or moderate liver problems process or breakdown the study drug GW679769 in their bodies as compared to healthy subjects.


Eligibility criteria: Inclusion criteria:

* Healthy or have mild or moderate hepatic impairment
* Females: Non-childbearing (hysterectomy, bilateral oophorectomy, post-menopausal), childbearing (negative pregnancy test, abstinence, double-barrier contraception, vasectomized partner)
* Negative for Hepatitis B and C(healthy subjects)
* Negative drug, alcohol and HIV tests

Exclusion criteria:

* Fluctuating or rapidly deteriorating hepatic function or abnormal kidney function
* Encephalopathy
* Active peptic ulcer disease
* Drug or alcohol abuse
* Pregnant or lactating
* Esophageal bleeding
* Heart failure
* Infection

Primary outcomes:
measure: Area under the concentration-time curve (AUC) of single oral dose of GW679769 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: AUC of multiple oral dose of GW679769 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: AUC of single oral dose of GW679769 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: AUC of multiple oral dose of GW679769 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: Maximum observed concentration (Cmax) of single oral dose of GW679769 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: Cmax of multiple oral dose of GW679769 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: Cmax of single oral dose of GW679769 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: Cmax of multiple oral dose of GW679769 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: AUC of single oral dose of GSK525060 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: AUC of multiple oral dose of GSK525060 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: AUC of single oral dose of GSK525060 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: AUC of multiple oral dose of GSK525060 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: Cmax of single oral dose of GSK525060 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: Cmax of multiple oral dose of GSK525060 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: Cmax of single oral dose of GSK525060 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: Cmax of multiple oral dose of GSK525060 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
Secondary outcomes:
Other outcomes:
measure: Time to maximum observed concentration (tmax) of single oral dose of GW679769 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: tmax of multiple oral dose of GW679769 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: tmax of single oral dose of GW679769 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: tmax of multiple oral dose of GW679769 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: tmax of single oral dose of GSK525060 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: tmax of multiple oral dose of GSK525060 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: tmax of single oral dose of GSK525060 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: tmax of multiple oral dose of GSK525060 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: Terminal half-life (t1/2) of single oral dose of GW679769 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: t1/2 of multiple oral dose of GW679769 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: t1/2 of single oral dose of GW679769 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: t1/2 of single oral dose of GW679769 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: t1/2 of single oral dose of GSK525060 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: t1/2 of multiple oral dose of GSK525060 in healthy subjects
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: t1/2 of single oral dose of GSK525060 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
measure: t1/2 of multiple oral dose of GSK525060 in subjects with mild and moderate hepatic impairment
timeFrame: Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours, Pre-dose (Day 3 and 4), Day 5 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours
measure: Percentage of unbound GW679769 in healthy subjects receiving single oral dose of GW679769
timeFrame: 1, 2, 4 and 24 hours post-dose on Day 1
measure: Percentage of unbound GW679769 in healthy subjects receiving multiple oral dose of GW679769
timeFrame: 1, 2, 4 and 24 hours post-dose on Day 1. Day 5, Pre-dose, 1, 2, 4, 24 hours post-dose
measure: Percentage of unbound GW679769 in subjects with mild and moderate hepatic impairment receiving single oral dose of GW679769
timeFrame: 1, 2, 4 and 24 hours post-dose on Day 1
measure: Percentage of unbound GW679769 in subjects with mild and moderate hepatic impairment receiving multiple oral dose of GW679769
timeFrame: 1, 2, 4 and 24 hours post-dose on Day 1. Day 5, Pre-dose, 1, 2, 4, 24 hours post-dose
measure: Percentage of unbound GSK525060 in healthy subjects receiving single oral dose of GSK525060
timeFrame: 1, 2, 4 and 24 hours post-dose on Day 1
measure: Percentage of unbound GSK525060 in healthy subjects receiving multiple oral dose of GSK525060
timeFrame: 1, 2, 4 and 24 hours post-dose on Day 1. Day 5, Pre-dose, 1, 2, 4, 24 hours post-dose
measure: Percentage of unbound GSK525060 in subjects with mild and moderate hepatic impairment receiving single oral dose of GSK525060
timeFrame: 1, 2, 4 and 24 hours post-dose on Day 1
measure: Percentage of unbound GSK525060 in subjects with mild and moderate hepatic impairment receiving multiple oral dose of GSK525060
timeFrame: 1, 2, 4 and 24 hours post-dose on Day 1. Day 5, Pre-dose, 1, 2, 4, 24 hours post-dose
measure: Number of subjects with Adverse events (AE) and Serious AEs (SAE)
timeFrame: Up to Day 22
measure: Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP)
timeFrame: Up to Day 22
measure: Number of subjects with abnormal heart rate
timeFrame: Up to Day 22
measure: Number of subjects with abnormal hematology parameters
timeFrame: Up to Day 22
measure: Number of subjects with abnormal clinical chemistry parameters
timeFrame: Up to Day 22
measure: Number of subjects with abnormal urinalysis
timeFrame: Up to Day 22
Locations:
city: Gainesville
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: