Healthy subjects vs subjects with asthma or COPD MedDRA version: 12.1 Level: LLT Classification code 10003553 Term: Asthma MedDRA version: 12.1 Level: LLT Classification code 10010952 Term: COPD
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 80mL/min calculated by the Cockcroft-Gault equation using serum creatinine. Renally Impaired Subjects 10. AST and ALT 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 11. Creatinine clearance < 30mL/min calculated by the Cockcroft-Gault equation using serum creatinine. 12. Subjects with renal insufficiency must have stable renal function defined as = 25% difference in creatinine clearance assessed on two occasions. Renal function will be based on estimated creatinine clearance (CLcr) calculated by the Cockcroft-Gault equation using serum creatinine obtained on two occasions separated by at least 4 weeks within the last 3 months (historic data is permitted for the first measurement). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects fo
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. Any subject with either documented cirrhosis or a history consistent with a diagnosis of cirrhosis. 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 within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 8. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 9. Use of nephrotoxic medications 4 weeks before dosing. 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 with smoking history of >10 cigarettes per day or regular use of tobacco- or nicotine-containing products, within 6 months prior to screening. 18. History of severe milk protein allergy. 19. Any adverse reaction including immediate or delayed hypersensitivity to any beta2- agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the Novel DPI (i.e., lactose or magnesium stearate). History of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. 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 21. If, in the opinion of the examining physician, an unstable cardiovascular, renal, hepatic, pulmonary, endocrine, metabolic, neurological, haematological or gastrointestinal condition is present or any other medical condition which the investigator considers sufficiently serious to interfere with the conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject. 22. Subjects with any predisposing condition that might interfere with the absorption, distribution, metabolism or excretion of drugs or any previous gastrointestinal (GI) surgery please view page 25 of the protocol for further information. 23. Urinary tract or bladder infection within 4 weeks of the first scheduled administration of study drug. 24. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. 25. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 26. History of regular alcohol consumption within 6 months of the study defined as: • An
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To investigate the effect of severe renal impairment on the pharmacokinetics of FF and GW642444 following repeat administration of FF/ GW642444M (200/25mcg)via NDPI;Secondary Objective: • To investigate the effect of severe renal impairment on cortisol suppression following repeat administration of FF/ GW642444 (200/25mcg) via NDPI • To investigate the effect of severe renal impairment on heart rate following repeat administration of FF/ GW642444 (200/25mcg) via NDPI • To investigate the effect of severe renal impairment on potassium following repeat administration of FF/ GW642444M (200/25mcg) via a NDPI • To investigate the effect of severe renal impairment on safety and tolerability following repeat administration of FF/ GW642444 (200/25mcg) via 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
Outcome results
None listed