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A Study to Evaluate the Effect of GSK1322322 on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers

Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Infections, Bacterial

Intervention: GSK1322322 1200 mg (Drug); GSK1322322 3000 mg (Drug); Placebo (Drug); Moxifloxacin (Drug)

Phase: Phase 1

Status: Withdrawn

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline


This is a randomized, partially-blinded, placebo and moxifloxacin-controlled, single dose, 4-period, balanced crossover study. The primary objective of this study is to separately assess the effects of a therapeutic and supratherapeutic dose of GSK1322322 on the cardiac conduction (corrected QT interval [QTc]) compared with placebo in eligible healthy male and female subjects. Avelox (moxifloxacin hydrochloride) will be used as an open-label positive control in order to validate the sensitivity of the study in detecting QTc change. Approximately 56 healthy subjects will participate in the study for approximately 9 weeks i. e. 30 day Screening period, 4-week Treatment period, and a 7-10 day Follow-up period. There will be 4 treatment periods separated by at least 1 week. Subjects will be admitted to

the clinical unit on Day - 1 of each dosing period. Each subject will receive each of the

four treatment sequences (GSK1322322 1200 milligram [mg] intravenous [IV] over 60 minutes x 1 dose, GSK1322322 3000 mg IV over 60 minutes x 1 dose, GSK1322322 Placebo IV over 60 minutes x 1 dose, moxifloxacin 400 mg administered orally x 1 dose) on Day 1 of each Treatment period in a randomized fashion. Twelve-lead electrocardiogram (ECG), continuous Holter monitoring, laboratory tests, vital sign measurements, and serial pharmacokinetic samples will be collected for up to 24 hours following each treatment. If no clinically significant abnormalities are noted, subjects will be discharged from the clinical research unit after the completion of all assessments on Day 2 in each period and return approximately one week later for the next dosing period. Each individual subject will follow the same dosing schedule at every period. A Follow-up visit will be conducted 7-10 days after administration of the last dose of study medication in treatment period 4.

Clinical Details

Official title: A Phase I, Randomized, Partially Blinded, Placebo- and Moxifloxacin-Controlled, 4-Period Crossover Study to Evaluate the Effect of GSK1322322 on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers (PDF112166)

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

Primary outcome: Change from baseline in QT duration corrected for heart rate by Fridericia's formula (QTcF) for GSK1322322 as compared with time-matched placebo

Secondary outcome:

Change from baseline in QT duration corrected for heart rate by Bazett's formula (QTcB), Individual (linear) QT correction (QTci), QT, and heart rate (HR)

Change from baseline in QTcB, QTci, QT, and HR

Plasma concentrations and selected pharmacokinetic (PK) parameters of moxifloxacin

Plasma concentrations and selected PK parameters of GSK1322322/moxifloxacin

Safety and tolerability of GSK1322322 as assessed by change from baseline in 12-lead ECGs

Safety and tolerability of GSK1322322 as assessed by change from baseline in vital signs

Safety and tolerability of GSK1322322 as assessed by number of subjects with adverse events

Safety and tolerability of GSK1322322 as assessed by change from baseline in toxicity grading of clinical laboratory tests


Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.


Inclusion Criteria:

- 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 feels that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures

- Male or female (of non childbearing potential) between 18 and 65 years of age

inclusive, at the time of signing the informed consent

- 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 milli international units [mIU]/millilitre [mL] and estradiol <40 picograms [pg]/mL or <147 picomole [pmol]/litre [L] is confirmatory)

- Male subjects with female partners of child-bearing potential must agree to use one

of the following contraception methods from the time of the first dose of study

medication until the final follow up visit - Condom plus partner use of a highly

effective contraceptive; Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e. g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception

- Body weight >=50 kilograms (kg) for men and >=45 kg for women and body mass index

(BMI) within the range 18. 5-31. 0 kg/(square metre) m^2 (inclusive)

- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1. 5 x Upper

limit of normal (ULN) (isolated bilirubin >1. 5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening and check-in (repeat allowed at check-in only)

- Serum Potassium, Calcium and Magnesium lab parameters within normal limits at

screening and check-in (repeat allowed at check-in only)

- QTcB <450 milliseconds (msec) at screening and check-in

- Capable of giving written informed consent, which includes compliance with the

requirements and restrictions listed in the consent form Exclusion Criteria:

- History/evidence of any arrhythmia (for example, first, second or third degree heart

block, atrial fibrillation, supraventricular tachycardia, sinus bradycardia, junctional rhythm) or clinically significant cardiac disease or procedure(mitral valve regurgitation, heart murmur, angina/ischemia, congenital heart abnormalities, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA). Personal or family history of long QT syndrome

- Subjects with a pre-existing condition interfering with normal gastrointestinal

anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy, inflammatory bowel disease or pancreatitis. Subjects with active peptic ulcer disease or a history of upper gastrointestinal bleeding

- Current or chronic history of liver disease, or known hepatic or biliary

abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)

- History of regular alcohol consumption within 6 months of the study defined as an

average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1. 5 ounces (45 mL) of 80 proof distilled spirits

- A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody

result, or a positive test for Human Immunodeficiency Virus (HIV) antibody within 3 months of screening

- A positive pre-study drug/alcohol screen

- 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: 30 days, 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

- Unable to refrain from the use of prescription or non-prescription drugs, including

vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety due to potential drug interaction

- History of sensitivity to any of the study medications, quinolone antibiotics,

(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

- Where participation in the study would result in donation of blood or blood products

in excess of 500 mL within a 56 day period

- Pregnant females as determined by positive (serum or urine) Human chorionic

gonadotropin (hCG) test at screening or prior to dosing

- Lactating females

- Unwillingness or inability to follow the procedures outlined in the protocol

- Subject is mentally or legally incapacitated

- History of sensitivity to heparin or heparin-induced thrombocytopenia

- Urinary cotinine levels indicative of smoking or history or regular use of tobacco-

or nicotine-containing products within 6 months prior to screening

- Unable to refrain from consumption of red wine, seville oranges, grapefruit or

grapefruit juice (and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices) from 7 days prior to the first dose of study medication

- Exclusion criteria for screening Holter and ECG (a single repeat is allowed for

eligibility determination): Heart rate <45 and >100 beats per minute (bpm) for males or <50 and >100 bpm for females; PR Interval <120 and >220 msec; QRS duration <70 and >120 msec; QTc interval (Bazett) >=450 msec (Note: The waveforms must enable the QT interval to be clearly defined); Q wave >30 msec

- Evidence of previous myocardial infarction (does not include ST segment changes

associated with repolarization)

- Any conduction abnormality (including but not specific to left or right bundle branch

block, Atrioventricular (AV) block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses>3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject

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Additional Information

Starting date: August 2014
Last updated: January 26, 2015

Page last updated: August 23, 2015

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