Corrected QT (QTc) Study With Flucticasone Furoate and GW642444

NCT01209026 | Completed Phase 1

• 1 other identifier: 102936
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma

Keywords

Fluticasone furoate (GW685698); moxifloxacin; QTc; GW642444; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline and Day 7

Secondary Outcomes (6)

• 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.

  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

  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.

  Baseline and Day 7

• Maximal change from baseline on Day 7 for QTcF, QTci and QTcB (for all treatments)

  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)

  Baseline and Day 7

Study Arms (4)

FF/GW642444M (200/25mcg)

EXPERIMENTAL

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; Drug: Placebo Inhaler; Drug: Moxifloxacin placebo

FF/GW642444M (800/100 mcg)

EXPERIMENTAL

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; Drug: Moxifloxacin placebo

Moxifloxacin

ACTIVE COMPARATOR

Inhaled placebo on Days 1-7; moxifloxacin (400mg po SD) on Day 7

Drug: Placebo Inhaler; Drug: Moxifloxacin 400mg

Placebo

PLACEBO COMPARATOR

Inhaled placebo on Days 1-7; placebo tablet (po SD) on Day 7.

Drug: Placebo Inhaler; Drug: Moxifloxacin placebo

Interventions

Fluticasone furoate (200 mcg)/GW642444 (25mcg) combination DRUG

Novel dry powder inhaler

FF/GW642444M (200/25mcg)

Fluticasone furoate (400 mcg)/GW642444 (50mcg) combination DRUG

Novel dry powder inhaler

FF/GW642444M (800/100 mcg)

Placebo Inhaler DRUG

Matching placebo Novel dry powder inhaler. Lactose monohydrate and magnesium stearate.

FF/GW642444M (200/25mcg); Moxifloxacin; Placebo

Moxifloxacin 400mg DRUG

Film coated oral tablet

Moxifloxacin

Moxifloxacin placebo DRUG

Film coated oral tablet

FF/GW642444M (200/25mcg); FF/GW642444M (800/100 mcg); Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Publications (1)

• 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 Mar;77(3):466-79. doi: 10.1111/bcp.12243.

  PMID: 24093504 DERIVED

Related Links

• Results for study 102936 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Asthma

Interventions

fluticasone furoate; Moxifloxacin

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2010
• First Posted: September 24, 2010
• Study Start: June 23, 2010
• Primary Completion: January 4, 2011
• Study Completion: January 4, 2011
• Last Updated: June 8, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)