A Study to Assess the Effects of Fluticasone Furoate and GW642444M Combination in Healthy Subjects and in Subjects With Mild, Moderate or Severe Hepatic Impairment.

Asthma Clinical Trial

Official title: An Open-label, Non-randomized, Pharmacokinetic and Safety Study of Repeat Doses of Fluticasone Furoate and GW642444M Combination in Healthy Subjects and in Subjects With Mild, Moderate or Severe Hepatic Impairment

Status Completed

Clinical Trial Summary

In relation to their severity, hepatic diseases can significantly modify drug absorption and disposition and consequently can interfere with drug efficacy and/or produce toxicity. The purpose of this study will be to aid in deciding whether a dose adjustment is required in subjects with hepatic impairment and in estimating any such adjustments.

Clinical Trial Description

In relation to their severity, hepatic diseases can significantly modify drug absorption and disposition and consequently can interfere with drug efficacy and/or produce toxicity. Pathological modifications of liver structure or functionality might result in complex modifications of various factors including liver blood flow, hypoalbuminaemia, indirectly affect renal function and reduce the hepatic drug metabolizing capability including the microsomal oxidase system [Howden, 1989].

Although FF/GW642444M is delivered directly to the site of action, i.e. the lungs, a large portion of the administered dose is swallowed. For both FF and GW642444 any drug absorbed from the GI tract undergoes first pass metabolism via CYP3A4. In addition, drug absorbed into the systemic circulation is metabolised in the liver and removed by biliary clearance. Hence, there is a possibility that when used by patients with impaired liver function the pharmacokinetics of inhaled FF and/or GW642444 may be changed due to reduced first pass metabolism and/or reduced clearance. The results of this study will aid in deciding whether a dose adjustment is justified and in estimating any such adjustments in patients with impaired hepatic function.

This is an open-label, non-randomized study which will assess the pharmacokinetics and safety of inhaled FF 200mcg/GW642444M 25mcg in subjects with hepatic impairment following 7 days once daily dosing. Subjects with mild, moderate and severe hepatic impairment (as defined by a Child-Pugh score of 5-15) will be recruited along with healthy control subjects matched to the moderate subjects (matched on gender, ethnicity, body mass index +/-15%, age +/-5 years).

Approximately thirty-six subjects will be recruited: 9 subjects for each severity and 9 matched healthy subjects. All subjects are scheduled to receive FF 200mcg/GW642444M 25mcg once daily for 7 days. The dose for subjects with severe hepatic impairment may be adjusted to FF 100mcg/GW642444M 12.5mcg after review of the PK and safety data from the moderate and healthy matched control subjects. The results of this study will aid in deciding whether a dose adjustment is required in subjects with hepatic impairment and in estimating any such adjustments. ;

Related Conditions & MeSH terms

• Asthma
• Liver Diseases

• NCT number: NCT01266941
• Study type: Interventional
• Source: GlaxoSmithKline
• Status: Completed
• Phase: Phase 1
• Start date: October 18, 2010
• Completion date: July 15, 2011