Observational Pharmacokinetic Study Of GW679769 In Subjects With Renal Impairment

Study Overview
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Brief Summary
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The purpose of the study is to evaluate how subjects with mild or moderate kidney problems process or breakdown the study drug GW679769 in their bodies as compared to healthy subjects.

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

Conditions
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Vomiting

Intervention / Treatment
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* Drug: Casopitant


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy or have mild or moderate renal impairment. Females must be of non-childbearing potential(hysterectomy, bilateral oophorectomy, post-menopausal) OR childbearing and must have a negative pregnancy test and meet/comply with one of the following: abstinence, double-barrier contraception, vasectomized partner). Be negative for Hepatitis B and C. Have negative results on drug, alcohol and HIV tests. Have stable renal function. Exclusion criteria: Have a peptic ulcer. Abuse drugs or alcohol. Are pregnant or lactating. Have heart failure. Have uncontrolled emesis. Have an infection. Have taken or received inducers or inhibitors of CYP3A4 or CYP3A5 within 14 days of study start. Active peptic ulcer disease. Digoxin use. Laboratory results that show low iron or pepsinogen levels, AST and CK level >1,5 ULN, or that show stool is positive for occult blood.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects receiving casopitant<br>Eligible subjects will receive a 100 milligrams oral dose of casopitant once daily for five consecutive days. | Drug: Casopitant<br>* Casopitant oral tablets will be available with a dose of 50 milligrams.<br>* Other names: GW679769;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma drug concentration versus time curve from 0 to 24 hours (AUC[0-24]) of casopitant and GSK525060 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 16 hours on Day 1; pre-dose on Day 2, Day 3 and Day 4; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours on Day 5 | 
| Maximum observed concentration (Cmax) of casopitant and GSK525060 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 16 hours on Day 1; pre-dose on Day 2, Day 3 and Day 4; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours on Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximum observed plasma drug concentration (Tmax) of casopitant and GSK525060 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 16 hours on Day 1; pre-dose on Day 2, Day 3 and Day 4; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours on Day 5 | 
| Half-life of casopitant and GSK525060 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 16 hours on Day 1; pre-dose on Day 2, Day 3 and Day 4; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours on Day 5 | 
| Free fraction (percent unbound) of casopitant and GSK525060 | Blood samples will be collected for assessment of protein binding of casopitant and GSK525060. | 1,2,4 and 24 hours post-dose on Day 1; pre-dose,1,2,4 and 24 hours post-dose on Day 5 | 
| Number of subjects with adverse events (AEs) and serious adverse events (SAEs) | An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. | Up to Day 22 | 
| Number of subjects with abnormal values for blood pressure | Systolic (SBP) and diastolic blood pressure (DBP) will be measured. | Up to Day 22 | 
| Number of subjects with abnormal values for heart rate | Heart rate will be measured. | Up to Day 22 | 
| Number of subjects with abnormal findings after weight measurement | Weight evaluation will be performed as measure of safety. | Up to Day 22 | 
| Number of subjects having abnormal hematology laboratory parameters as a measure of safety | Hematology parameters will be analyzed as a measure of safety. | Up to Day 22 | 
| Number of subjects having abnormal clinical Chemistry laboratory parameters as a measure of safety | Clinical chemistry parameters will be analyzed as a measure of safety. | Up to Day 22 | 
| Number of subjects having abnormal values for urinalysis as a measure of safety | Urinalysis will be carried out as a measure of safety. | Up to Day 22 | 
| Number of subjects with abnormal findings after serological tests | Serological tests will be performed as a measure of safety. | Up to Day 22 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal impairment, emesis, GW679769, kidney problems