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Infections, BacterialPhase 1NCT01803399

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

A Phase 1 study testing GSK1322322 1200 mg, GSK1322322 3000 mg and Moxifloxacin in people with Infections, Bacterial, run by GlaxoSmithKline.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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])… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Infections, Bacterial
What is being tested?
GSK1322322 1200 mg, GSK1322322 3000 mg and Moxifloxacin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Aug 2014to Dec 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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

About this study

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)

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.

Being tested
GSK1322322 1200 mg, GSK1322322 3000 mg, Placebo, Moxifloxacin
Keywords
cardiac repolarization, oral, QTc, GSK1322322, antibiotic, 12-lead ECG, placebo, IV, moxifloxacin
Medical subject headings
Bacterial Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK1322322 1200 mgDrug

    GSK1322322 will be supplied as white to slightly colored lyophilized powder 400 mg/vial for injection. Single dose of GSK1322322 1200 mg (3 vials) will be administered IV over 60 minutes

  • GSK1322322 3000 mgDrug

    GSK1322322 will be supplied as white to slightly colored lyophilized powder 400 mg/vial for injection. Single dose of GSK1322322 3000 mg (8 vials) will be administered IV over 60 minutes

  • PlaceboDrug

    Placebo will be supplied as 0.9% sodium chloride solution. Single dose of placebo will be administered IV over 60 minutes

  • MoxifloxacinDrug

    Moxifloxacin will be supplied as oblong, dull red film coated tablets of 400 mg strength. Single dose of moxifloxacin 400 mg will be administered orally

Study groups in NCT01803399
Study groupRoleWhat they receive
GSK1322322 1200 mg ArmExperimentalEach subject will receive a single dose of GSK1322322 1200 mg IV over 60 minutes on Day 1 of one of the 4 treatment periods
Receives: Drug: GSK1322322 1200 mg
GSK1322322 3000 mg ArmExperimentalEach subject will receive a single dose of GSK1322322 3000 mg IV over 60 minutes on Day 1 of one of the 4 treatment periods
Receives: Drug: GSK1322322 3000 mg
Placebo ArmPlacebo comparatorEach subject will receive a single dose of GSK1322322 Placebo IV over 60 minutes on Day 1 of one of the 4 treatment periods
Receives: Drug: Placebo
Moxifloxacin 400 mg ArmActive comparatorEach subject will receive a single dose of moxifloxacin 400 mg administered orally on Day 1 of one of the 4 treatment periods
Receives: Drug: Moxifloxacin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Triplicate 12-lead Holter ECG measurements for each subject at each time point will be averaged

    Measured: Day 1: -1.5, -1.0 and -0.5 hours pre-dose (average as baseline) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose (Day 2) of each treatment period

Secondary outcomes (8)

  1. 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)

    To estimate the effect of single dose IV GSK1322322 (1200 mg and 3000 mg) as compared with placebo. Triplicate 12-lead Holter ECG measurements for each subject at each time point will be averaged

    Measured: Day 1: -1.5, -1.0 and -0.5 hours pre-dose (average as baseline) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose (Day 2) of each treatment period

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

    To estimate the effect of single dose oral moxifloxacin (400 mg) as compared to placebo. Triplicate 12-lead Holter ECG measurements for each subject at each time point will be averaged

    Measured: Day 1: -1.5, -1.0 and -0.5 hours pre-dose (average as baseline) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose (Day 2) of each treatment period

  3. Plasma concentrations and selected pharmacokinetic (PK) parameters of moxifloxacin

    PK parameters will include: maximum observed plasma concentration (Cmax); time to Cmax (tmax); area under the plasma concentration-time curve (AUC): from time zero (pre-dose) to last time of quantifiable concentration [AUC (0-t)], from time zero (pre-dose) to 24 hours [AUC (0-24)], and from time zero (pre-dose) extrapolated to infinite time [AUC (0-∞)]; apparent terminal phase half-life (t1/2); Systemic clearance of parent drug (CL); and volume of distribution at steady state (Vss), as data permit

    Measured: Day 1: 15 minutes pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose (Day 2) of each treatment period

  4. Plasma concentrations and selected PK parameters of GSK1322322/moxifloxacin

    To characterize the PK/pharmacodynamics (PD) relationship between GSK1322322/moxifloxacin plasma concentrations (and other PK parameters, if appropriate) and QTcF, QTcF changes relative to placebo (ddQTcF) , QTcB, and QTci

    Measured: Day 1: 15 minutes pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose (Day 2) of each treatment period

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

    Single 12-lead ECGs will be obtained

    Measured: Screening, Day 1 (pre-dose (x3) [mean value as baseline] and 0.5, 1, 1.5, 4, 8, 12 hours post-dose) of each treatment period, and Week 9

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

    Vital sign measurements will include systolic and diastolic blood pressure, temperature and HR

    Measured: Screening, Day 1 (pre-dose (x3) [mean value as baseline] and 0.5, 1, 1.5, 4, 8, 12 hours post-dose) of each treatment period, and Week 9

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

    Measured: Through 9 weeks

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

    Clinical laboratory tests will include clinical Chemistry, hematology and urinalysis assessments

    Measured: Through 9 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2013 (estimated)
  2. Study startAug 2014
  3. Primary completionDec 2014 (estimated)
  4. Study completionDec 2014 (estimated)

Why it stopped: Emerging GSK1322322 pre-clinical data ID'd potentially reactive metabolites previously not seen that changed the risk: benefit profile and led to a termination

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01803399
Sponsor's protocol ID
112166
Status last verified
Jan 2015
First submitted
28 Feb 2013
Last updated
28 Jan 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1322322 1200 mg, GSK1322322 3000 mg and Moxifloxacin in people with Infections, Bacterial, run by GlaxoSmithKline.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 28 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline in QT duration corrected for heart rate by Fridericia's formula (QTcF) for GSK1322322 as compared with time-matched placebo (time frame: Day 1: -1.5, -1.0 and -0.5 hours pre-dose (average as baseline) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose (Day 2) of each treatment period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01803399.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2015.

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