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Corrected QT (QTc) Study With Flucticasone Furoate and GW642444

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01209026
First received: September 23, 2010
Last updated: August 30, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Fluticasone furoate (200 mcg)/GW642444 (25mcg) combination
Drug: Fluticasone furoate (400 mcg)/GW642444 (50mcg) combination
Drug: Placebo Inhaler
Drug: Moxifloxacin 400mg
Drug: Moxifloxacin placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 [ Time Frame: Baseline and Day 7 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. [ Time Frame: Baseline and Day 7 ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: Baseline and Day 7 ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Baseline and Day 7 ] [ Designated as safety issue: Yes ]
  • Maximal change from baseline on Day 7 for QTcF, QTci and QTcB (for all treatments) [ Time Frame: Baseline and Day 7 ] [ Designated as safety issue: Yes ]
  • Change from baseline at each timepoint on Day 7 for other cardiac electrophysiological parameters: QT, QRS, RR, PR and ventricular rate (for all treatments) [ Time Frame: Baseline and Day 7 ] [ Designated as safety issue: Yes ]
  • 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)) [ Time Frame: Study duration ] [ Designated as safety issue: No ]

Enrollment: 85
Study Start Date: June 2010
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FF/GW642444M (200/25mcg)
Inhaled fluticasone furoate (200mcg) /GW642444M (25mcg) combination Days 1- 7; placebo tablet taken orally single dose (po SD) on Day 7.
Drug: Fluticasone furoate (200 mcg)/GW642444 (25mcg) combination
Novel dry powder inhaler
Drug: Placebo Inhaler
Matching placebo Novel dry powder inhaler. Lactose monohydrate and magnesium stearate.
Drug: Moxifloxacin placebo
Film coated oral tablet
Experimental: FF/GW642444M (800/100 mcg)
Inhaled fluticasone furoate (800mcg) /GW642444M (100mcg) combination Days 1- 7; placebo tablet (po SD) on Day 7.
Drug: Fluticasone furoate (400 mcg)/GW642444 (50mcg) combination
Novel dry powder inhaler
Drug: Moxifloxacin placebo
Film coated oral tablet
Active Comparator: Moxifloxacin
Inhaled placebo on Days 1-7; moxifloxacin (400mg po SD) on Day 7
Drug: Placebo Inhaler
Matching placebo Novel dry powder inhaler. Lactose monohydrate and magnesium stearate.
Drug: Moxifloxacin 400mg
Film coated oral tablet
Placebo Comparator: Placebo
Inhaled placebo on Days 1-7; placebo tablet (po SD) on Day 7.
Drug: Placebo Inhaler
Matching placebo Novel dry powder inhaler. Lactose monohydrate and magnesium stearate.
Drug: Moxifloxacin placebo
Film coated oral tablet

Detailed Description:

This is a randomised, placebo controlled, four way crossover thorough QT study to evaluate the effect of repeat dose fluticasone furoate/GW642444M combination on the QTc interval in healthy male and female subjects. Up to 85 subjects will receive inhaled placebo and inhaled fluticasone furoate/GW642444M combination (200/25 microgram (mcg) or 800/100 mcg) and oral moxifloxacin (400 milligram (mg)). The inhaled treatments will be given double-blind once daily in the morning for 7 days with a single-blind placebo tablet also administered on Day 7. Moxifloxacin (positive control) will be given as a single-blind single dose on Day 7 in the morning with inhaled double-blind placebo administered in the morning on Days 1-7. Individual time-matched changes from baseline in QT duration corrected for heart rate by Fredericia's formula (QTcF) (difference from placebo) for fluticasone furoate/GW642444M 200/25mcg will be determined 0-24 hours (h) after dosing on Day 7 (primary endpoint). Secondary endpoints will include changes from baseline in QTcF, QT individual correction factor (QTci), QT duration corrected for heart rate by Bazett's formula (QTcB), and QT interval at each timepoint after 7 days dosing of fluticasone furoate/GW642444M 800/100mcg and single dose oral moxifloxacin (400mg) and changes from baseline in QTci, QTcB, and QT interval at each timepoint after 7 days dosing of fluticasone furoate/GW642444M 200/25mcg. Plasma concentrations (0-24h) and pharmacokinetic parameters of GW642444 and fluticasone furoate will also be derived.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  • A female subject is eligible to participate if she is of:

    • 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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01209026

Locations
United Kingdom
GSK Investigational Site
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01209026     History of Changes
Other Study ID Numbers: 102936
Study First Received: September 23, 2010
Last Updated: August 30, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Ethics Committee

Keywords provided by GlaxoSmithKline:
Fluticasone furoate (GW685698)
moxifloxacin
QTc
GW642444
pharmacokinetics

Additional relevant MeSH terms:
Fluticasone
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Allergic Agents
Anti-Asthmatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antineoplastic Agents
Autonomic Agents
Bronchodilator Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Combined
Dermatologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Respiratory System Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014