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

• Conditions: healthy subjects and in subjects with mild, moderate or severe hepatic impairment; MedDRA version: 12.1Level: LLTClassification code 10052254Term: Hepatic impairment

• Registration Number: EUCTR2010-020157-13-SK
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-07
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 36

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 <
40 pg/ml (<140 pmol/L) (healthy subjects only) is confirmatory]. Females on
hormone replacement therapy (HRT) and whose menopausal status is in doubt
will be required to use one of the contraception methods in Section 8.1 if they
wish to continue their HRT during the study. Otherwise, they must discontinue
HRT to allow confirmation of post-menopausal status prior to study enrollment.
For most forms of HRT, at least 2-4 weeks will elapse between the cessation of
therapy and the blood draw; this interval depends on the type and dosage of
HRT. Following confirmation of their post-menopausal status, they can resume
use of HRT during the study without use of a contraceptive method.
• Child-bearing potential and agrees to use one of the contraception methods
listed in Section 8.1 for an appropriate period of time (as determined by the
product label or investigator) prior to the start of dosing to sufficiently minimize
the risk of pregnancy at that point. Female subjects must agree to use
contraception until completion of the follow-up visit.
3. BMI within the range 19 – 33 kg/m2.
4. Able to satisfactorily use the dry powder inhalation inhaler.
5. Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
6. Single QTcF < 450 msec; or QTcF < 480 msec in subjects with Bundle Branch
Block.
Healthy subjects
1. AST, ALT, alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin
>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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified