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

This study has been withdrawn prior to enrollment.
(Study was terminated due to toxicology findings after screening started but before first subject first dose.)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01721135
First received: November 1, 2012
Last updated: August 20, 2013
Last verified: August 2013
  Purpose

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 .


Condition Intervention Phase
Asthma
Drug: GSK2190915 100mg
Drug: GSK2190915 200mg
Drug: moxifloxacin 400mg
Drug: moxifloxacin placebo
Drug: GSK2190915 placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Placebo Controlled, Four-way Cross-over Study to Assess Cardiac Re-polarisation Following Repeat Dosing With GSK2190915 and Placebo for Five Days, With Moxifloxacin as a Positive Control, in Healthy Male and Female 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 Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for 100mg GSK2190915 as compared with time-matched placebo [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • 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)) [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • Heart rate and ECG parameters taken on Day 1 and Day 5 compared with concentration of Plasma GSK2190915 to find relationship [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • Maximal change from baseline on Day 5 for QTcF and QTcB [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • Change from baseline at each timepoint on Day 5 for other cardiac electrophysiological parameters: QT, QRS, RR, PR and ventricular rate [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • Assessment of safety and tolerability of GSK2190915 by 12-lead ECGs, vital signs, adverse events and clinical laboratory tests throughout treatment period [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: September 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2190915 100mg
GSK2190915 100mg on days 1-5; moxifloxacin placebo on day 5
Drug: GSK2190915 100mg
Film coated oral tablet
Drug: moxifloxacin placebo
Film coated oral tablet
Drug: GSK2190915 placebo
Film coated oral tablet
Experimental: GSK2190915 1000mg
GSK2190915 1000mg on days 1-5; moxifloxacin placebo on day 5
Drug: GSK2190915 200mg
Film coated oral tablet
Drug: moxifloxacin placebo
Film coated oral tablet
Active Comparator: moxifloxacin 400mg
placebo tablet on days 1-5; moxifloxacin 400mg on day 5
Drug: moxifloxacin 400mg
Film coated oral tablet
Drug: GSK2190915 placebo
Film coated oral tablet
Placebo Comparator: placebo
placebo tablet on days 1-5; moxifloxacin placebo on day 5
Drug: moxifloxacin placebo
Film coated oral tablet
Drug: GSK2190915 placebo
Film coated oral tablet

Detailed Description:

This is a randomized, placebo controlled, four way crossover thorough QT study to evaluate the effect of repeat dose GSK2190915 on the QTc interval in healthy male and female subjects. Approximately 48 subjects will receive oral placebo, GSK2190915 (100mg or 1000mg) and moxifloxacin (400mg). GSK2190915 or matching placebo will be given once daily for 5 days with a moxifloxacin matching placebo given on Day 5. Moxifloxacin (positive control) will be given as a single-blind single dose on Day 5 with placebo administered on Days 1-4. Individual time-matched changes from baseline in QTcF (difference from placebo) for GSK2190915 will be determined 0-24 hours after dosing on Day 5 (primary endpoint). Secondary endpoints will include changes from baseline in QTcF, QTcB and QT interval at each timepoint after 5 days dosing of GSK2190915 and single dose moxifloxacin (400mg). Plasma concentrations on Day 5 (0-24 hours) and pharmacokinetic parameters of GSK2190915 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 ≤ 1.5x 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

Exclusion Criteria:

  • 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
  • Pregnant females
  • Lactating females
  • Unwillingness or inability to follow the procedures outlined in the protocol
  • Subject is mentally or legally incapacitated
  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: NCT01721135

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

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01721135     History of Changes
Other Study ID Numbers: 112360
Study First Received: November 1, 2012
Last Updated: August 20, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
moxifloxacin
GSK2190915
pharmacokinetics
QTc

Additional relevant MeSH terms:
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Combined
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014