healthy subjects and in subjects with mild, moderate or severe hepatic impairment MedDRA version: 12.1 Level: LLT Classification code 10052254 Term: Hepatic impairment
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent. 2. A female subject is eligible to participate if she is of: • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 2. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or outcome. Hepatically Impaired Subjects 1. Hepatically impaired. To be classified as hepatically impaired, subjects must have: Known medical history of liver disease with or without a known history of alcohol abuse; and A Child-Pugh score of 5-15 to cover all severities (Mild = 5-6 points; Moderate = 7- 9 points; Severe = 10-15 points). The components that contribute to the CP score should be directly related to the underlying hepatic disease and not to non-hepatic disease. 2. Subjects with no significant abnormality, apart from impaired hepatic function and related symptoms, or clinical examination. A subject with a clinical abnormality may be included only if the Investigator considers that the abnormality will not introduce additional risk factors and will not interfere with the study procedures. Hepatically impaired subjects with other laboratory parameters outside the reference ranges will only be included if, in the opinion of the Investigator, the result
Exclusion criteria
Exclusion criteria: 1. Suffered a lower respiratory tract infection in the 4 weeks before the screening visit. 2. Taken oral corticosteroids less than 8 weeks before the screening visit. 3. Taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit. 4. Have a known sensitivity to corticosteroids and/or long acting beta agonists. 5. A positive pre-study drug/alcohol screen. 6. A positive test for HIV antibody. 7. The subject has participated in a clinical trial and has received an investigational product view page 26 of the protocol for further information. 8. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 9. History of sensitivity to any of the study medications, or components view page 26 of the protocol for further information. 10. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. 11. Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing. 12. Lactating females. 13. The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness. 14. Unwillingness or inability to follow the procedures outlined in the protocol. 15. Subject is mentally or legally incapacitated. 16. History of sensitivity to heparin or heparin-induced thrombocytopenia. 17. Subjects who have asthma or a history of asthma. 18. History of severe milk protein allergy. 19. Subjects with a smoking history of >10 cigarettes per day or regular use of tobacco or nicotine-containing products, within 6 months prior to screening. 20. Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication. Healthy subjects 1. If, in the opinion of the examining physician, an unstable cardiovascular, renal, hepatic condition, view page 26 of the protocol for further information. 2. Subjects with any predisposing condition that might interfere with the absorption, distribution, metabolism or excretion of drugs or any previous gastrointestinal (GI) surgery (view page 27 of the protocol for further information. 3. Haemoglobin values <12.9g/dL for males and <11.4g/dL for females. 4. A past history or current symptoms of significant hepatic or renal disease, pancreatitis or acute cholecystitis view page 27 of the protocol for further information. 5. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening 6. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 7. History of regular alcohol consumption within 6 months of the study defined as: View page 26 of the protocol. 8. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements view page 27 of the protocol for further information. 1. If in the opinion of the examining physician, an unstable cardiovascular, renal, pulmonary condition, view page 26 of the protocol for further information. 2. Severe ascities (Child-Pugh ascites score of 3) upon clinical exam, including physical exam and abdominal ultrasound at screening. View page 26 of the protocol page for further information. 3. History of oesophageal bleeding within the last 6 months before do
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of varying degrees of hepatic impairment on the pharmacokinetics of FF and GW642444 following repeat administration of FF 200mcg/GW642444M 25mcg via a novel Dry Powder Inhaler (NDPI).;Secondary Objective: •To investigate the effect of varying degrees of hepatic impairment on serum cortisol suppression following repeat administration of FF 200mcg/GW642444M 25mcg via a NDPI. • To investigate the effect of varying degrees of hepatic impairment on heart rate following repeat administration of FF 200mcg/GW642444M 25mcg via a NDPI. • To investigate the effect of varying degrees of hepatic impairment on serum potassium following repeat administration of FF 200mcg/GW642444M 25mcg via a NDPI. • To investigate the effect of varying degrees of hepatic impairment on safety and tolerability following repeat administration of FF 200mcg/GW642444M 25mcg via a NDPI.;Primary end point(s): • Fluticasone furoate and GW642444 pharmacokinetics (AUC(0-t), AUC (0-8), Cmax, tmax) on Day 1 and 7 and AUC(0-24) and t½ on Day 7. | — |
Countries
Czech Republic, Slovakia
Outcome results
None listed