Last updated: 11/06/2018 23:59:51
Corrected QT (QTc) study with flucticasone furoate and GW642444
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A randomised, placebo-controlled, four-way crossover repeat dose study to evaluate the effect of the inhaled fluticasone furoate (FF)/GW642444M combination on electrocardiographic parameters, with moxifloxacin as a positive control, in healthy subjects
Trial description: A randomised, placebo controlled thorough QTc study to evaluate the effect of repeat dose FF/GW642444M combination, with moxifloxacin as a positive control, on the QTc interval in healthy male and female subjects. Key assessments will include 12- lead electrocardiogram (ECG) and pharmacokinetic (PK) parameters, along with safety being assessed by blood pressure, heart rate, clinical laboratory safety tests, and collection of adverse events.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from baseline in QTcF interval at each timepoint on study Day 7 (average of at least 3 Holter ECG replicates per time point) for fluticasone furoate/GW642444M 200/25mcg as compared with time-matched placebo
Timeframe: Baseline and Day 7
Secondary outcomes:
Change from baseline in QTcF interval at each timepoint on study Day 7 (average of at least 3 Holter ECG replicates per time point) for fluticasone furoate/GW642444M 800/100mcg as compared with time-matched placebo.
Timeframe: Baseline and Day 7
Change from baseline in QTci and QTcB interval at each timepoint on Study Day 7 (average of at least 3 Holter ECG replicates per time point) for fluticasone furoate/GW642444M 200/25mcg and 800/100mcg as compared with time-matched placebo
Timeframe: Baseline and Day 7
Change from baseline in QTcF interval at each timepoint on Study Day 7 (average of at least 3 Holter ECG replicates per time point) for moxifloxacin as compared with time-matched placebo.
Timeframe: Baseline and Day 7
Maximal change from baseline on Day 7 for QTcF, QTci and QTcB (for all treatments)
Timeframe: Baseline and Day 7
Change from baseline at each timepoint on Day 7 for other cardiac electrophysiological parameters: QT, QRS, RR, PR and ventricular rate (for all treatments)
Timeframe: Baseline and Day 7
Plasma concentrations of GW642444 and fluticasone furoate and derived pharmacokinetic parameters including maximum observed concentration(Cmax), time of occurence of Cmax (tmax), Area under the concentration-time curve over the dosing interval (AUC(0-τ))
Timeframe: Study duration
Interventions:
Enrollment:
85
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Kempsford R, Allen A, Kelly K, Saggu P, Crim C.A repeat-dose thorough QT study of inhaled fluticasone furoate/vilanterol combination in healthy subjects.Br J Clin Pharmacol.2014;77(3):466-79
Medical condition
Asthma
Product
fluticasone furoate, vilanterol
Collaborators
Not applicable
Study date(s)
June 2010 to January 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- Male or female between 18 and 65 years of age inclusive.
- Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin ≤ 1.5xUpper limit of normal (ULN).
- Subject is deemed unsuitable for the study.
- A screening Holter ECG tracing that reveals clinically concerning arrhythmias
Inclusion and exclusion criteria
Inclusion criteria:
- Male or female between 18 and 65 years of age inclusive.
- Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin ≤ 1.5xUpper limit of normal (ULN).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- Non-childbearing potential defined as pre-menopausal females with tubal ligation or hysterectomy, and post-menopausal females. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods. All other female subjects must agree to use contraception until 4 months post-last dose.
- Body Mass Index (BMI) within 18.5-29.0 kilograms/metre2.
- Capable of giving written informed consent.
- Subjects who are current non-smokers, who have not used any tobacco products in the 6 month period preceding the screening visit.
- No significant abnormality on 12-lead ECG at screening.
- A 24 hour Holter ECG at screening which shows no abnormalities that could affect study data.
- Forced Expiratory Volume in 1 second (FEV1) ≥ 85% predicted at screening.
- Subjects who are able to use the inhaler satisfactorily.
A female subject is eligible to participate if she is of:
Exclusion criteria:
- Subject is deemed unsuitable for the study.
- A screening Holter ECG tracing that reveals clinically concerning arrhythmias
- A supine blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg) at screening.
- A supine mean heart rate outside the range 40-90 beats per minute (bpm) at screening.
- History or presence of any medically significant disease or disorder, in particular, a family history of QT prolongation, of early or sudden cardiac death or of early cardiovascular disease.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- The subject has any history of breathing problems in adult life.
- Subjects who have suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit.
- Pregnant females.
- Lactating females.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for Human Immunodeficiency Virus (HIV) antibody.
- The subject has taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit.
- Positive carbon monoxide (CO) or alcohol breath test at screening or on admission to the Unit.
- Positive urine cotinine test at screening.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females.
- The subject has participated in a clinical trial in the last 3 months.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days of the first dose.
- The subject has taken oral corticosteroids less than 8 weeks before the screening visit.
- History of sensitivity to any of the study medications.
- History of milk protein allergy.
- Where participation in the study would result in donation of blood or blood products in excess of 500 millilitres (mL) within a 90 day period.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- Consumption of seville oranges, pommelos (members of the grapefruit family) or grapefruit juice from 7 days prior to the first dose of study medication.
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
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2011-04-01
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.
Additional information about the trial
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Additional information
Results for study 102936 can be found on the GSK Clinical Study Register.
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