A Drug Interaction Study With Fluticasone Furoate/GW642444 Inhalation Powder and Ketoconazole
Information source: GlaxoSmithKline
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Asthma
Intervention: ketoconazole (placebo to match) (Drug); FF / GW642444 (Drug); ketoconazole (Drug)
Phase: Phase 1
Sponsored by: GlaxoSmithKline
Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline
US GSK Clinical Trials Call Center, Phone: 877-379-3718
A randomized two-way crossover study to determine whether concomitant administration of CYP
P450 3A4 inhibitor ketoconazole and fluticasone furoate/GW642444M combination significantly
increases the systemic effects and exposure to repeat dose fluticasone furoate and/or
GW642444 in healthy subjects. Key assessments will include blood potassium, heart rate,
blood pressure, QTc, serum cortisol and pharmacokinetic parameters, and safety including
vital signs, ECGs, adverse event monitoring and laboratory safety tests, including blood
Official title: A Double-blind, Randomized, Placebo-controlled, Repeat Dose, 2-way Crossover Drug Interaction Study to Investigate the Pharmacokinetic and Pharmacodynamic Effects Following Administration of Fluticasone Furoate/GW642444M Inhalation Powder With Ketoconazole
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator)
Weighted mean serum cortisol (0-24 hours) on Day 11.
Maximum heart rate (0-4 hours) and minimum blood potassium level (0-4 hours) on the morning of Day 11
Minimum diastolic blood pressure (0-4 hours), maximum systolic blood pressure (0-4 hours) and maximum QTcF (0-4 hours) on the morning of Day 11
Fluticasone furoate and GW642444 pharmacokinetics (AUC(0-t), AUC(0-24), Cmax, tmax) on Day 5 and 11
Reported adverse events
12-lead ECG and clinical laboratory data and maximum heart rate (0-4 hours) maximum QTc (0-4 hours) and minimum blood potassium and blood glucose levels (0-4 hours) on the morning of Day 5.
This will be a single centre, randomized, double-blind (with respect to ketoconazole),
two-way cross-over study in healthy male and female subjects. Subjects will attend for a
screening visit within 28 days prior to the first treatment period. There will be two study
periods, each consisting of 14 days. Ketoconazole or matching placebo will be administered
for 11 days with fluticasone furoate/GW642444M inhalation powder co-administered on Days
5-11. During each period subjects will be required to report to the unit on Day - 1 and will
remain there until 1 hour post-dosing with ketoconazole or placebo on Day 1. Subjects will
return to the unit on the mornings of Day 2 to Day 4 for dosing with ketoconazole or
placebo. Subjects will then return on the evening of Day 4 and leave the unit on the morning
of Day 6 (2 nights). Subjects will return to the unit on the mornings of Day 7 to Day 10
for dosing and pre-fluticasone furoate/GW642444M dose safety assessments. Subjects will
return on the evening of Day 10 and leave the unit on the morning of Day 12 (2 nights).
Subjects will make two outpatient visits, one in the evening on Day 12 and one in the
morning on Day 13, to complete a few study related procedures. The two treatment periods
will be separated by a washout of at least 7 days and no more than 14 days. Pharmacodynamic
profiles for potassium, heart rate, QTc, blood pressure and serum cortisol will be taken on
Day 11 with fluticasone furoate and GW642444 pharmacokinetic profiles on Days 5 and 11.
Safety assessments will include vital signs, ECGs, adverse event monitoring and laboratory
safety tests, plus blood glucose and blood potassium profiles on Day 5.
Minimum age: 18 Years.
Maximum age: 64 Years.
1. Healthy male or female between 18 and 64 years of age inclusive
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) 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. Body mass index within range of 18. 5-29. 0 kg/m2 inclusive.
4. Subjects who are current non-smokers, who have not used any tobacco products in the
12 month period preceding the screening visit, and have a pack history of = 5 pack
5. AST, ALT, alkaline phosphatase and bilirubin = 1. 5xULN (isolated bilirubin >1. 5xULN
is acceptable if bilirubin is fractionated and direct bilirubin <35%).
6. No significant abnormality on 12-lead ECG at screening, including the following
- QTcF < 450 msec
7. No clinically significant abnormality on the Holter ECG at screening.
8. FEV1 >/= 85% predicted at screening.
9. Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
10. Able to satisfactorily use the dry powder inhaler.
1. As a result of medical interview, physical examination or screening investigations,
the principal investigator or delegate physician deems the subject unsuitable for the
study. Subjects must not have a systolic blood pressure above 145 mmHg or a diastolic
pressure above 85 mmHg unless the Investigator confirms that it is satisfactory for
2. The subject has any history of breathing problems in adult life (i. e. history of
3. Pregnant females as determined by positive serum hCG test at screening or by positive
serum/urine hCG test prior to dosing.
4. Lactating females.
5. The subject has been treated for or diagnosed with depression within six months of
screening or has a history of significant psychiatric illness.
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. Subjects who have suffered a lower respiratory tract infection within 4 weeks of the
8. History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or GSK
Medical Monitor, contraindicates their participation.
9. Any adverse reaction including immediate or delayed hypersensitivity to any
beta-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic
corticosteroid therapy. Known or suspected sensitivity to the constituents of the
new powder inhaler (ie lactose or magnesium stearate)
10. History of milk protein allergy.
11. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John's Wort) within 7 days (or 14 days if the drug is a
potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first
dose of study medication, unless in the opinion of the Investigator and GSK Medical
Monitor the medication will not interfere with the study procedures or compromise
12. The subject has taken oral corticosteroids less than 8 weeks before the screening
13. The subject has taken inhaled, intranasal or topical steroids less than 4 weeks
before the screening visit.
14. History of alcohol/drug abuse or dependence within 12 months of the study. Abuse of
alcohol defined as an average weekly intake of greater than 21 units or an average
daily intake of greater than 3 units (males) or defined as an average weekly intake
of greater than 14 units or an average daily intake of greater than 2 units
15. 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: 3 months, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).
16. Exposure to more than four new chemical entities within 12 months prior to the first
17. Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within 3 months of the start of the trial.
18. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.
19. The subject has tested positive for HIV antibodies.
20. A positive pre-study urine drug screen or when randomly tested during the study.
21. Positive carbon monoxide (CO) or alcohol breath test at screening or on admission to
22. Consumption of seville oranges, pomelos (members of the grapefruit family) or
grapefruit juice from 7 days prior to the first dose of study medication.
23. Unwillingness or inability to follow the procedures outlined in the protocol.
24. Subject is mentally or legally incapacitated.
Locations and Contacts
US GSK Clinical Trials Call Center, Phone: 877-379-3718
GSK Investigational Site, London NW10 7EW, United Kingdom; Recruiting
Steve Warrington, Principal Investigator
Starting date: July 2010
Last updated: July 16, 2010