A Study to Evaluate the Effect of Two Different Repeat Doses of GSK2190915 on the QTc Interval.

NCT01721135 | Withdrawn Phase 1

• 1 other identifier: 112360
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, placebo controlled, four way crossover, in which the the effect of GSK2190915 on the QTc interval is assessed. Healthy subjects will recieve a 5 day course of each of the following; oral placebo, GSK2190915 100mg, GSK2190915 1000mg and moxifloxacin 400mg (single dose) with a weeks washout prior to starting the next course. Key assessments include a 12- lead electrocardiogram and pharmacokinetic testing. Safety will be assessed by blood pressure, heart rate, clinical laboratory safety tests and collection of adverse events .

Conditions

Asthma

Keywords

moxifloxacin; GSK2190915; pharmacokinetics; QTc

Outcome Measures

Primary Outcomes (1)

• Change from baseline in QTcF interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for 100mg GSK2190915 as compared with time-matched placebo

  5 days

Secondary Outcomes (8)

• Change from baseline in QTcF interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for 1000mg GSK2190915 as compared with time-matched placebo

  5 days

• Change from baseline in QTcB interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for 100mg and 1000mg GSK2190915 as compared with time-matched placebo

  5 days

• Change from baseline in QTcF interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for moxifloxacin as compared with time-matched placebo

  5 days

• Plasma concentrations of GSK2190915 taken on Day 5 to derive pharmacokinetic parameters including Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax) and Area under the concentration-time curve over the dosing interval (AUC(0-τ))

  5 days

• Heart rate and ECG parameters taken on Day 1 and Day 5 compared with concentration of Plasma GSK2190915 to find relationship

  5 days

Study Arms (4)

GSK2190915 100mg

EXPERIMENTAL

GSK2190915 100mg on days 1-5; moxifloxacin placebo on day 5

Drug: GSK2190915 100mg; Drug: moxifloxacin placebo; Drug: GSK2190915 placebo

GSK2190915 1000mg

EXPERIMENTAL

GSK2190915 1000mg on days 1-5; moxifloxacin placebo on day 5

Drug: GSK2190915 200mg; Drug: moxifloxacin placebo

moxifloxacin 400mg

ACTIVE COMPARATOR

placebo tablet on days 1-5; moxifloxacin 400mg on day 5

Drug: moxifloxacin 400mg; Drug: GSK2190915 placebo

placebo

PLACEBO COMPARATOR

placebo tablet on days 1-5; moxifloxacin placebo on day 5

Drug: moxifloxacin placebo; Drug: GSK2190915 placebo

Interventions

GSK2190915 100mg DRUG

Film coated oral tablet

GSK2190915 100mg

GSK2190915 200mg DRUG

Film coated oral tablet

GSK2190915 1000mg

moxifloxacin 400mg DRUG

Film coated oral tablet

moxifloxacin 400mg

moxifloxacin placebo DRUG

Film coated oral tablet

GSK2190915 1000mg; GSK2190915 100mg; placebo

GSK2190915 placebo DRUG

Film coated oral tablet

GSK2190915 100mg; moxifloxacin 400mg; 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 ≤ 1.5x Upper limit of normal (ULN)
• Healthy as determined by a 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 a documented tubal ligation or hysterectomy; or postmenopausal . Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods. Those of child-bearing potential must agree to use one of the protocol contraception methods.
• Body mass index (BMI) within the range 18.5-29.0 kg/m2 (inclusive)
• Capable of giving written informed consent
• Current non-smokers who have not used tobacco products in the 6 month period preceding screening
• No significant abnormality on 12-lead electrocardiogram (ECG) at screening
• A 24 hour Holter ECG at screening that demonstrates no clinically significant abnormalities

You may not qualify if:

• A physician deems the subject unsuitable for the study
• A screening Holter ECG tracing that reveals clinically concerning arrhythmias
• A blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg) at screening.
• A mean heart rate outside the range 40-90 beats per minute (bpm) at screening.
• History or presence of any medically significant disease, or any disorder. In particular, a family history of QT prolongation, of early or sudden cardiac death or of early cardiovascular disease.
• A positive result for Hepatitis B or Hepatitis C within 3 months of screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities
• A positive pre-study drug/alcohol screen
• A positive test for Human Immunodeficiency Virus (HIV) antibody
• History of regular alcohol consumption within 6 months of the study
• The subject has participated in a clinical trial and has received an investigational product within 3 months of the first dosing day in the current study
• 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 from 14 days before screening until the follow-up visit unless permitted by the investigator
• History of sensitivity to any of the study medications
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 3 month period

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

3-(3-tert-butylsulfanyl-1-(4-(6-ethoxypyridin-3-yl)benzyl)-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropionic acid; 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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: November 5, 2012
• Study Start: September 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: August 21, 2013

Record last verified: 2013-08

Locations

GB (1)