QTc Study GSK573719+GW642444

NCT01521377 | Completed Phase 1

• 1 other identifier: 114635
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, placebo controlled, four period incomplete block,crossover thorough QT study to estimate the effect of repeat dose GSK573719/GW642444M (Vilanterol) combination and GSK573719 monotherapy on the QTc interval in healthy male and female subjects compared with placebo. At least 100 subjects will receive, four of five possible, 10-day repeat dose treatments. Treatments are placebo with a moxifloxacin placebo on day 10, placebo with moxifloxacin (400mg) on day 10, GSK573719/Vilanterol combination (125/25μg) with moxifloxacin placebo on day 10, GSK573719/Vilanterol combinatio (500/100μg) with moxifloxacin placebo on day 10, or GSK573719 (500μg) with a moxifloxacin placebo on day 10. All treatments are double blind except for moxifloxacin (400mg) and moxifloxacin placebo controls, given as a single-blind single dose on Day 10 of the appropriate treatment period. Primary endpoints are individual time-matched changes from baseline QTcF for GSK573719/Vilanterol combination (125/25μg) and GSK573719 (500μg), 0-24 hours after dosing on Day 10. Secondary endpoints will include individual time-matched changes from baseline in QTcF for GSK573719/Vilanterol combination (500/100μg) and moxifloxacin (400mcg) 0-24 hours after dosing on Day 10. Also changes from baseline in QTci, QTcB, QT, QRS, RR, PR and ventricular rate at each time point after 10 days dosing of each GSK573719 and GSK573719/Vilanterol treatment and single dose moxifloxacin (400mg). Maximal change from baseline 0-24hours after dosing on day 10 will be derived for QTcF, QTci and QTcB for each treatment. Plasma concentrations on Day 10 (0-24 hours) and pharmacokinetic parameters of GSK573719 and Vilanterol will also be derived. Key assessments: 12- lead electrocardiogram (ECG), pharmacokinetics. Safety will be assessed by blood pressure, heart rate, clinical laboratory safety tests and collection of adverse events (AEs).

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

LAMA; Respiratory; COPD; Tolerability; Beta-2 Agonist; Safety; Pharmacokinetics; Pharmacodynamics; LABA; Muscarinic Receptor Agonist; Healthy subjects; Moxifloxacin; Anticholinergic; GW642444; GSK573719; QTc

Outcome Measures

Primary Outcomes (2)

• Change from baseline in QTcF Interval with GSK573719/ Vilanterol 125/25mcg

  To estimate the effect of GSK573719/ Vilanterol 125/25mcg on the QTcF interval as compared with placebo after 10 days dosing.

  Screening, Day 1, and Day 10

• Change from baseline in QTcF Interval with GSK573719 500 mcg

  To estimate the effect of GSK573719 500 mcg (four times the highest combination dose being evaluated in Phase III trials) on the QTcF interval as compared with placebo after 10 days dosing.

  Screening, Day 1, and Day 10

Secondary Outcomes (8)

• Change from baseline in QTcF interval with GSK573719/Vilanterol 500/100mcg

  Screening, Day 1, and Day 10

• Change from baseline in QTci and QTcB interval for GSK573719/Vilanterol 125/25mcg and 500/100mcg as compared with timematched placebo.

  Screening, Day 1, and Day 10

• Change from baseline in QTci and QTcB interval for GSK573719 500mcg as compared with time-matched placebo.

  Screening, Day 1, and Day 10

• Change from baseline in QTcF interval for moxifloxacin as compared with time-matched placebo.

  Screening, Day 1, and Day 10

• Change from baseline in QTci and QTcB interval for moxifloxacin as compared with time-matched placebo.

  Screening, Day 1, and Day 10

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Single inhalation from matching placebo dry powder inhaler once daily on days 1-10. Single dose placebo oral tablet moxifloxacin.

Drug: Placebo Moxifloxacin; Drug: Placebo DPI

Moxifloxacin Positive

ACTIVE COMPARATOR

Single inhalation from matching placebo dry powder inhaler once daily on days 1-10. Single dose oral tablet moxifloxacin (400mg) on day 10.

Drug: Moxifloxacin; Drug: Placebo DPI

GSK573719 Supra-therapeutic dose

EXPERIMENTAL

Single inhalation from GSK573719 (500 microgram) dry powder inhaler once daily on days 1-10. Single dose placebo oral moxifloxacin.

Drug: Placebo Moxifloxacin; Drug: GSK573719

GSK573719/Vilanterol Therapeutic dose

EXPERIMENTAL

Single inhalation from GSK573719/Vilanterol (125/25 microgram) dry powder inhaler once daily on days 1-10. Single dose placebo oral tablet moxifloxacin on day 10.

Drug: Placebo Moxifloxacin; Drug: GSK573719/Vilanterol 125/25mcg

GSK573719/Vilanterol Supra-therapeutic dose

EXPERIMENTAL

Single inhalation from GSK573719/Vilanterol (500/100 microgram) dry powder inhaler once daily on days 1-10. Single dose placebo oral tablet moxifloxacin on day 10.

Drug: Placebo Moxifloxacin; Drug: GSK573719/Vilanterol 500/100mcg

Interventions

Placebo Moxifloxacin DRUG

Single dose placebo oral tablet Moxifloxacin

GSK573719 Supra-therapeutic dose; GSK573719/Vilanterol Supra-therapeutic dose; GSK573719/Vilanterol Therapeutic dose; Placebo

Moxifloxacin DRUG

Single oral dose tablet Moxifloxacin (400mg)

Moxifloxacin Positive

GSK573719/Vilanterol 125/25mcg DRUG

Single inhalation from GSK573719/Vilanterol 125/25mcg DPI once daily

GSK573719/Vilanterol Therapeutic dose

GSK573719 DRUG

Single inhalation from GSK573719 500mcg DPI once daily

GSK573719 Supra-therapeutic dose

GSK573719/Vilanterol 500/100mcg DRUG

Single inhalation from GSK573719/Vilanterol 500/100mcg DPI once daily

GSK573719/Vilanterol Supra-therapeutic dose

Placebo DPI DRUG

Single Inhalation from matching Placebo DPI once daily

Moxifloxacin Positive; 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, at the time of signing the informed consent.
• 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 subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator believes that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• 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 \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \<40 pg/ml (\<147 pmol/L) is confirmatory\]. 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 after the Follow Up visit
• AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Body weight ≥ 45 kg and BMI within the range 18 - 29.5 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• No significant abnormality on 12-lead ECG at screening, including the following specific requirements:
• Ventricular rate ≥ 40 beats per minute
• PR interval ≤ 210msec
• Q waves \< 30msec (up to 50 ms permitted in lead III only)
• QRS interval to be ≥ 60msec and \< 120msec
• The waveforms must enable the QT interval to be clearly defined
• QTcF interval must be \< 450msec (machine or manual reading).

You may not qualify if:

• History or presence of any medically significant disease, or any disorder that would introduce additional risk or interfere with the study procedures or outcome. In particular, a family history of QT prolongation, of early or sudden cardiac death or of early cardiovascular disease.
• History of symptomatic 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 of tendon disease/disorder related to quinolone treatment.
• History of sensitivity to any of the study medications, including moxifloxacin, 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. In particular, the subject has a known allergy or hypersensitivity to quinolones, ipratropium bromide, tiotropium, atropine and any of its derivatives. Or any adverse reaction including immediate or delayed hypersensitivity to any β2 agonist or sympathomimetic drug,
• Severe Milk Protein allergy
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• 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. One unit is equivalent to 8 g of alcohol: a half-pint (\~240 ml) of beer, 1 glass (125ml) of wine or 1 (25 ml) measure of spirits.
• 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).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Links

• Results for study 114635 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

Pulmonary Disease, Chronic Obstructive

Interventions

Moxifloxacin; GSK573719; vilanterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2012
• First Posted: January 30, 2012
• Study Start: December 19, 2011
• Primary Completion: June 5, 2012
• Study Completion: June 5, 2012
• Last Updated: June 12, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)