Investigating The Pharmacokinetics Of An Inhaled Dose Of A New Corticosteroid In Patients With Impaired Liver Function

Study Overview
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Brief Summary
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The proposed study is designed to investigate the pharmacokinetics, pharmacodynamics (as measured by serum cortisol) and safety of GW685698X in subjects with moderate hepatic impairment and in healthy subjects following a single oral inhaled dose of GW685698X. From the study results it should be possible to assess if there is an altered Risk: Benefit in patients with moderate hepatic impairment

Official Title
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A Study to Investigate the Pharmacokinetics of a Single Inhaled Dose (400mcg) of GW685698X and Its Effect on Serum Cortisol in Patients With Impaired Liver Function and Matched Control Subjects.

Conditions
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Asthma

Intervention / Treatment
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* Drug: GW685698X


Participation Criteria
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Eligibility Criteria
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Inclusion: Are aged between 18-70 years, inclusive. If Female, you must be incapable of becoming pregnant. Show FEV1 of more than 70% of the predicted normal at screening. Are able to correctly use a DISKUS at the screening visit. Have Body Mass Index within the range of 19-33 kg/m2 inclusive. Do not show a positive pre-study urine drug screen. Do not show a positive pre-study blood alcohol test. Demonstrate a clinically normal 12-lead ECG at screening. Do not show a positive blood test for HIV. If you are a Healthy Volunteer you must also: Have no significant abnormality on clinical examination. Have Liver Function Tests within the reference range at screening. If you are a Patient Volunteer you must: Have moderate hepatic impairment Have no significant abnormality on clinical examination apart from hepatic impairment. Exclusion: Suffered an upper respiratory infection in the 4 weeks before the screening visit. Suffered a lower respiratory infection in the 6 weeks before the screening visit. Taken oral corticosteroids in the 8 weeks before the screening visit. Taken inhaled, intranasal or topical steroids in the 4 weeks before the screening visit. A prolonged heartbeat (QTc interval >470msec). High blood pressure (systolic >160mmHg or diastolic >90mmHg) or as defined by the Investigator. Known sensitivity to corticosteroids. A history of lactose intolerance. A history of severe milk protein allergy. Donated blood in the last 3 months, or more than 1500mL (1000mL if female) in the last 12 months (including the amount taken for this study). Participated in a clinical trial within the last 3 months where you are/were exposed to a drug or device.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: Healthy subjects<br>Subjects with normal liver function test will be administered a single oral inhaled dose of 400 micrograms (mcg) GW685698X in the morning of the study day. Each healthy subject will be matched as closely as possible for age, gender, bodyweight and race to a subject with impaired liver function. | Drug: GW685698X<br>* GW685698X will be available as dry white powder to be inhaled via DISKUS containing cellobiose octaacetate (COA) blended with lactose.<br>|
| Experimental: Subjects with hepatic impairment<br>Subjects with Child Pugh B hepatic dysfunction will be administered a single oral inhaled dose of 400 mcg GW685698X in the morning of the study day. | Drug: GW685698X<br>* GW685698X will be available as dry white powder to be inhaled via DISKUS containing cellobiose octaacetate (COA) blended with lactose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate how impaired liver function affects the movement of single dose inhaled drug GW685698X within the body. Blood exposure levels in patients and matched control patients compared by taking blood samples after dosing |  | Up to Day 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of GW685698X on serum cortisol by calculating weighted mean in blood over 24 hrs. Safety and tolerability of GW685698X in patients with impaired liver function from blood samples during dosing (clearance/distribution) and monitoring vital signs |  | Up to Day 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatic impairment pharmacokinetics