Observational Study Evaluating The Processing Or Breakdown Of GW679769 In Subjects With Hepatic Impairment

Vomiting Clinical Trial

Official title:

An Open-Label, Non-Randomized, Pharmacokinetic and Safety Study of Multiple Oral Doses of GW679769 in Subjects With Hepatic Impairment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00359177
• Other study ID #: NKT102785
• Status: Completed
• Phase: Phase 1
• First received: July 28, 2006
• Last updated: September 21, 2017
• Start date: December 1, 2005
• Est. completion date: October 12, 2006

Study information

• Verified date: September 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 12, 2006
• Est. primary completion date: October 12, 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Liver Diseases
• Vomiting

Intervention

Drug:
• GW679769
GW679769 will be available in dose strength of 50 mg tablets. Subjects will receive two tablets of 50 mg orally once daily in the morning

Locations

Country	Name	City	State
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to maximum observed concentration (tmax) of single oral dose of GW679769 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. tmax will be calculated from plasma GW679769 concentration-time data.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Other	tmax of multiple oral dose of GW679769 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. tmax will be calculated from plasma GW679769 concentration-time data.	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
Other	tmax of single oral dose of GW679769 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. tmax will be calculated from plasma GW679769 concentration-time data.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Other	tmax of multiple oral dose of GW679769 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. tmax will be calculated from plasma GW679769 concentration-time data.	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
Other	tmax of single oral dose of GSK525060 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. tmax will be calculated from plasma GSK525060 concentration-time data.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Other	tmax of multiple oral dose of GSK525060 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. tmax will be calculated from plasma GSK525060 concentration-time data.	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
Other	tmax of single oral dose of GSK525060 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. tmax will be calculated from plasma GSK525060 concentration-time data.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Other	tmax of multiple oral dose of GSK525060 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. tmax will be calculated from plasma GSK525060 concentration-time data.	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
Other	Terminal half-life (t1/2) of single oral dose of GW679769 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. t1/2 will be calculated from plasma GW679769 concentration-time data.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Other	t1/2 of multiple oral dose of GW679769 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. t1/2 will be calculated from plasma GW679769 concentration-time data.	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
Other	t1/2 of single oral dose of GW679769 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. t1/2 will be calculated from plasma GW679769 concentration-time data.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Other	t1/2 of single oral dose of GW679769 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. t1/2 will be calculated from plasma GW679769 concentration-time data.	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
Other	t1/2 of single oral dose of GSK525060 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. t1/2 will be calculated from plasma GSK525060 concentration-time data.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Other	t1/2 of multiple oral dose of GSK525060 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. t1/2 will be calculated from plasma GSK525060 concentration-time data.	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
Other	t1/2 of single oral dose of GSK525060 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. t1/2 will be calculated from plasma GSK525060 concentration-time data	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Other	t1/2 of multiple oral dose of GSK525060 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. t1/2 will be calculated from plasma GSK525060 concentration-time data	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
Other	Percentage of unbound GW679769 in healthy subjects receiving single oral dose of GW679769	Blood samples for PK analysis will be collected at the indicated time points. Percentage of unbound GW679769 will be calculated from plasma GW679769 concentration-time data.	1, 2, 4 and 24 hours post-dose on Day 1
Other	Percentage of unbound GW679769 in healthy subjects receiving multiple oral dose of GW679769	Blood samples for PK analysis will be collected at the indicated time points. Percentage of unbound GW679769 will be calculated from plasma GW679769 concentration-time data	1, 2, 4 and 24 hours post-dose on Day 1. Day 5, Pre-dose, 1, 2, 4, 24 hours post-dose
Other	Percentage of unbound GW679769 in subjects with mild and moderate hepatic impairment receiving single oral dose of GW679769	Blood samples for PK analysis will be collected at the indicated time points. Percentage of unbound GW679769 will be calculated from plasma GW679769 concentration-time data.	1, 2, 4 and 24 hours post-dose on Day 1
Other	Percentage of unbound GW679769 in subjects with mild and moderate hepatic impairment receiving multiple oral dose of GW679769	Blood samples for PK analysis will be collected at the indicated time points. Percentage of unbound GW679769 will be calculated from plasma GW679769 concentration-time data.	1, 2, 4 and 24 hours post-dose on Day 1. Day 5, Pre-dose, 1, 2, 4, 24 hours post-dose
Other	Percentage of unbound GSK525060 in healthy subjects receiving single oral dose of GSK525060	Blood samples for PK analysis will be collected at the indicated time points. Percentage of unbound GSK525060 will be calculated from plasma GSK525060 concentration-time data.	1, 2, 4 and 24 hours post-dose on Day 1
Other	Percentage of unbound GSK525060 in healthy subjects receiving multiple oral dose of GSK525060	Blood samples for PK analysis will be collected at the indicated time points. Percentage of unbound GSK525060 will be calculated from plasma GSK525060 concentration-time data.	1, 2, 4 and 24 hours post-dose on Day 1. Day 5, Pre-dose, 1, 2, 4, 24 hours post-dose
Other	Percentage of unbound GSK525060 in subjects with mild and moderate hepatic impairment receiving single oral dose of GSK525060	Blood samples for PK analysis will be collected at the indicated time points. Percentage of unbound GSK525060 will be calculated from plasma GSK525060 concentration-time data.	1, 2, 4 and 24 hours post-dose on Day 1
Other	Percentage of unbound GSK525060 in subjects with mild and moderate hepatic impairment receiving multiple oral dose of GSK525060	Blood samples for PK analysis will be collected at the indicated time points. Percentage of unbound GSK525060 will be calculated from plasma GSK525060 concentration-time data.	1, 2, 4 and 24 hours post-dose on Day 1. Day 5, Pre-dose, 1, 2, 4, 24 hours post-dose
Other	Number of subjects with Adverse events (AE) and Serious AEs (SAE)	An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that at any dose may result in death, is life-threatening, may require hospitalization or prolongation of existing hospitalization, result in persistent disability/incapacity, or may led to any congenital anomaly or birth defect	Up to Day 22
Other	Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP)	Blood pressure measurement will be assessed in supine and resting position.	Up to Day 22
Other	Number of subjects with abnormal heart rate	Blood pressure measurement will be assessed in supine and resting position.	Up to Day 22
Other	Number of subjects with abnormal hematology parameters	Laboratory assessment for hematology parameters will include hemoglobin, hematocrit, red blood cell count (RBC), platelet count, white blood cell count (WBC), neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count, prothrombin time (PT), and International Normalized Ratio (INR)	Up to Day 22
Other	Number of subjects with abnormal clinical chemistry parameters	Laboratory assessment for clinical chemistry parameters sodium, potassium, chloride, total Carbon dioxide, calcium, glucose (fasting), phosphorous (inorganic), protein (total), albumin, gamma-glutamyl-transferase (GGT), bilirubin (total), alkaline Phosphatase, lactic dehydrogenase (LDH), aspartate aminotransferase (AST; Serum glutamic oxaloacetic transaminase), alanine aminotransferase (ALT; Serum glutamic pyruvic transaminase), creatinine, blood Urea Nitrogen, uric Acid, creatine Phosphokinase (CPK), and ammonia	Up to Day 22
Other	Number of subjects with abnormal urinalysis	Laboratory assessment for urinalysis parameters pH, specific gravity, glucose, protein, ketones, and blood	Up to Day 22
Primary	Area under the concentration-time curve (AUC) of single oral dose of GW679769 in healthy subjects	Blood samples for pharmacokinetics (PK) analysis will be collected at the indicated time points. AUC will be calculated from plasma GW679769 concentration.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Primary	AUC of multiple oral dose of GW679769 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. AUC will be calculated from plasma GW679769 concentration.	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
Primary	AUC of single oral dose of GW679769 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. AUC will be calculated from plasma GW679769 concentration.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Primary	AUC of multiple oral dose of GW679769 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. AUC will be calculated from plasma GW679769 concentration.	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
Primary	Maximum observed concentration (Cmax) of single oral dose of GW679769 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. Cmax will be calculated from plasma GW679769 concentration.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Primary	Cmax of multiple oral dose of GW679769 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. Cmax will be calculated from plasma GW679769 concentration.	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
Primary	Cmax of single oral dose of GW679769 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. Cmax will be calculated from plasma GW679769 concentration.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Primary	Cmax of multiple oral dose of GW679769 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. Cmax will be calculated from plasma GW679769 concentration.	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
Primary	AUC of single oral dose of GSK525060 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. AUC will be calculated from plasma GSK525060 concentration.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Primary	AUC of multiple oral dose of GSK525060 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. AUC will be calculated from plasma GSK525060 concentration.	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
Primary	AUC of single oral dose of GSK525060 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. AUC will be calculated from plasma GSK525060 concentration.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Primary	AUC of multiple oral dose of GSK525060 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. AUC will be calculated from plasma GSK525060 concentration.	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
Primary	Cmax of single oral dose of GSK525060 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. Cmax will be calculated from plasma GSK525060 concentration.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Primary	Cmax of multiple oral dose of GSK525060 in healthy subjects	Blood samples for PK analysis will be collected at the indicated time points. Cmax will be calculated from plasma GSK525060 concentration	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
Primary	Cmax of single oral dose of GSK525060 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. Cmax will be calculated from plasma GSK525060 concentration.	Day 1 Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours
Primary	Cmax of multiple oral dose of GSK525060 in subjects with mild and moderate hepatic impairment	Blood samples for PK analysis will be collected at the indicated time points. Cmax will be calculated from plasma GSK525060 concentration.	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

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•   Results for study NKT102785 can be found on the GSK Clinical Study Register.