Last updated: 11/07/2018 01:11:59
A drug interaction study with fluticasone furoate/GW642444 Inhalation Powder and ketoconazole
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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 glucose.
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Maximum heart rate (0-4 hours) and minimum blood potassium level (0-4 hours) on the morning of Day 11
Timeframe: Day 11
Weighted mean serum cortisol (0-24 hours) on Day 11.
Timeframe: Day 11
Secondary outcomes:
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
Timeframe: Day 11
Fluticasone furoate and GW642444 pharmacokinetics (AUC(0-t), AUC(0-24), Cmax, tmax) on Day 5 and 11
Timeframe: day 11
Reported adverse events
Timeframe: 2 months
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.
Timeframe: Day 5
Interventions:
Drug: FF / GW642444
Drug: ketoconazole
Drug: ketoconazole (placebo to match)
Enrollment:
18
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Kempsford R, Allen A, Bal J, Rubin D, Tombs L. The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of inhaled fluticasone furoate and vilanterol trifenate in healthy subjects. Br J Clin Pharmacol. 2013;75(6):1478-87.
Medical condition
Asthma
Product
fluticasone furoate, fluticasone furoate/vilanterol, ketoconazole, vilanterol
Collaborators
GSK
Study date(s)
July 2010 to August 2010
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 64 years
Accepts healthy volunteers
Yes
- 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:
- 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 their age.
- 2. The subject has any history of breathing problems in adult life (i.e. history of asthmatic symptomatology).
Inclusion and exclusion criteria
Inclusion criteria:
- 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 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 specific requirements:
- 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.
Exclusion criteria:
- 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 their age. 2. The subject has any history of breathing problems in adult life (i.e. history of asthmatic symptomatology). 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 screening visit. 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 subject safety. 12. The subject has taken oral corticosteroids less than 8 weeks before the screening visit. 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 (females). 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 dosing day. 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 the Unit. 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.
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2010-28-08
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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