Last updated: 11/07/2018 09:51:02

Placebo and Moxifloxacin Controlled Cardiac Conduction Study of GSK2140944 in Healthy Volunteers

Request patient level data
GSK study ID
115775
See study documents
Clinicaltrials.gov ID
NCT02257398
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Phase I, Randomized, Double-Blinded, Placebo- and Moxifloxacin-Controlled, 4-Period Crossover Study to Evaluate the Effect of GSK2140944 on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers
Trial description: This is Phase I, 4-period, randomized, active-and placebo-controlled, double-blind crossover, single-dose study to evaluate the effects of a therapeutic (1000 milligram [mg]) and supratherapeutic (1800 mg) dose of GSK2140944 with a positive control (moxifloxacin 400 mg) and placebo on the corrected QT interval (QTc) as assessed by continuous 12-lead Holter electrocardiograms (ECGs) in approximately 55 healthy volunteers.
All subjects will receive single doses of GSK2140944 1000 mg, GSK2140944 1800 mg, moxifloxacin 400 mg, and placebo in a randomized sequence. A double-dummy approach will be used to maintain blinding. Thus, on each dosing day, moxifloxacin or moxifloxacin placebo and GSK2140944 or placebo will be administered.
Subjects will be screened within 30 days prior to entry to the clinic. Subjects will report to the clinical unit on Day -2 of Period 1 and on Day -1 in subsequent periods. Subjects will remain confined until check out procedures have been completed on Day 3 (5 days confinement in Period 1 and 4 days in the following 3 periods). There will be a washout of at least 7 days between doses. The follow-up visit will occur 7-10 days after the final dose. Total duration of the study (from screening to the follow-up visit) will be approximately 60 days.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Change from baseline in corrected QT interval, using the Fridericia formula (QTcF) for GSK2140944 (1000 mg and 1800 mg)

Timeframe: Up to 48 hours

Secondary outcomes:

Change from baseline in ECG parameters for GSK2140944 (1000 mg and 1800 mg)

Timeframe: Up to 48 hours

Categorical outliers in ECG parameters for GSK2140944 (1000 mg and 1800 mg)

Timeframe: Up to 48 hours

Change from baseline in ECG parameters for moxifloxacin

Timeframe: Up to 48 hours

Composite of pharmacokinetic (PK) parameters for GSK2140944 (1000 mg and 1800 mg)

Timeframe: Up to 48 hours

Composite of PK parameters for moxifloxacin

Timeframe: Up to 48 hours

Plasma concentrations and change in QTcF for GSK2140944 and moxifloxacin

Timeframe: Up to 48 hours

Amount excreted (Ae) in urine of unchanged GSK2140944 (1000 mg and 1800 mg)

Timeframe: Up to 48 hours

Fraction of the dose (fe) excreted in urine

Timeframe: Up to 48 hours

Renal clearance

Timeframe: Up to 48 hours

Assessment of ECG

Timeframe: Up to Day 48

Change from baseline in vital sign measurements

Timeframe: Up to Day 48

Number of subjects with adverse events (AEs)

Timeframe: Up to Day 48

Toxicity grading of clinical laboratory test results

Timeframe: Up to Day 48

Interventions:
  • Drug: GSK2140944
  • Drug: GSK2140944 placebo
  • Drug: Moxifloxacin
  • Drug: Moxifloxacin placebo
    • Enrollment:
    55
    Primary completion date:
    Not applicable
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Hossain M, Zhou M, Tiffany C, Dumont E, Darpo B.A Phase I, Randomized, Double-Blinded, Placebo- and Moxifloxacin Controlled, 4-Period Crossover Study to Evaluate the Effect of Gepotidacin on Cardiac Conduction as Assessed by 12-Lead Electrocardiogram in Healthy Volunteers.Antimicrob Agents Chemother.2017;61(5):e02385-16
    Medical condition
    Infections, Respiratory Tract
    Product
    gepotidacin, moxifloxacin
    Collaborators
    Not applicable
    Study date(s)
    October 2014 to March 2015
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 55 years
    Accepts healthy volunteers
    Yes
    • Male or female between 18 and 55 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 feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
    • History/evidence of any arrhythmia (for example, second- or third-degree heart block, atrial fibrillation, supraventricular tachycardia, symptomatic 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 surgery, or percutaneous transluminal coronary angioplasty). A history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, and family history of long QT syndrome).
    • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert syndrome or asymptomatic gallstones).
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Male or female between 18 and 55 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 feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
    • Body weight >= 50 kilogram (kg) and body mass index within the range 19 to 31 kilogram / square meter (kg/m^2) (inclusive).
    • A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum beta-human chorionic gonadotrophin test), not lactating, and at least one of the following conditions applies:
    • Nonreproductive potential defined as:
    • Premenopausal females with one of the following: Documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy, documented bilateral oophorectomy.
    • Postmenopausal defined as 12 months of spontaneous amenorrhea. To confirm postmenopausal status, a blood sample for simultaneous follicle-stimulating hormone (FSH) >40 milli-international units per mililiter (mlU/mL) and estradiol <40 picogram/milliliter (pg/mL) (<147 picomole/liter [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 highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrolment.
    • Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study drug and until at least 7 days after the last dose of study drug and completion of the follow-up visit.
    • This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long-term and persistent basis.
    • Contraceptive subdermal implant that meets the standard operating procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label, intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label, oral contraceptive, either combined or progestogen alone, injectable progestogen, contraceptive vaginal ring, percutaneous contraceptive patches, male partner sterilization with documentation of azoospermia prior to the female subject’s entry into the study, and this male is the sole partner for that subject.
    • These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
    • Capable of giving signed informed consent as described in protocol, which includes compliance with the requirements and restrictions listed in the consent form and in the protocol
    • Alanine aminotransferase (ALT) and bilirubin <1.5 × upper limit of normal range (ULN). Isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%. One repeat test to confirm result is acceptable.
    • Serum potassium, calcium, and magnesium laboratory parameters within normal limits at screening and check-in.
    Exclusion criteria:
    • History/evidence of any arrhythmia (for example, second- or third-degree heart block, atrial fibrillation, supraventricular tachycardia, symptomatic 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 surgery, or percutaneous transluminal coronary angioplasty). A history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, and family history of long QT syndrome).
    • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert syndrome or asymptomatic gallstones).
    • Any clinically significant CNS (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic, or GI conditions or history of such conditions that, in the opinion of the investigator, may place the subject at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism, or excretion of drugs.
    • History of photosensitivity to quinolones.
    • Use of systemic antibiotic within 30 days of screening.
    • Confirmed lifetime history of C. difficile diarrhea
    • History of spontaneous tendon rupture
    • History of smoking or use of nicotine containing products within 3 months of screening or a positive urine cotinine indicative of smoking at screening.
    • 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 fluid ounces (fl oz) (360 millilitre [mL]) of beer, 5 fl oz (150 mL) of wine, or 1.5 fl oz (45 mL) of 80-proof distilled spirits.
    • History of sensitivity to any of the study drugs or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK medical monitor, contraindicates the potential subject’s participation.
    • History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain IV cannula patency).
    • A positive pre-study hepatitis B surface antigen or positive hepatitis C antibody result within 3 months of screening or positive human immunodeficiency virus (HIV) antibody.
    • A positive urine test for drugs of abuse at screening or at Day -1; positive urine test for alcohol (or alcohol breath test) within 24 hours of any dose in the study.
    • Exclusion criteria for screening and baseline ECG (a single repeat test is allowed for eligibility determination): Heart rate: <40 and >100 beats per minute (bpm) (For males), <45 and >100 bpm (For Females); PR interval<120 and >220 millisecond (msec); QRS duration<70 and >110 msec; QTcF interval>450 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 complete bundle branch block, atrioventricular block [second degree or higher], Wolff-Parkinson-White syndrome), sinus pauses >3 seconds, non-sustained or sustained ventricular tachycardia (>3 consecutive ventricular ectopic beats), or any significant arrhythmia that, in the opinion of the investigator and GSK medical monitor, will interfere with the safety of the individual subject.
    • An abnormal finding of clinical significance in the arrhythmia detection Holter performed on Day -2, which in the view of the investigator would compromise subject safety or interfere with study procedures or assessments will be excluded from the study. Full disclosures will be reviewed in detail and the review maintained as part of the subject’s source documents. Analysis of the Holter recordings will consider the following:
    • Heart rate (significant brady- or tachycardia, based on investigator’s judgment)
    • Reports of symptomatic arrhythmia (except isolated extrasystoles)
    • Normal and aberrant beats
    • Number of supraventricular contractions, premature atrial contractions, premature ventricular contractions, couplets, triplets, and ventricular tachycardias
    • Atrioventricular conduction defects
    • Atrial fibrillation and flutter
    • Participation in the study would result in a donation of blood or blood products in excess of 500 mL within a 56-day period.
    • Participation in a clinical trial in which the subject 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 4 new chemical entities within 12 months prior to the first dosing day.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Austin, Texas, United States, 78744
    Status
    Study Complete
    Contact us

    Study documents

    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Refer to study documents

    Recruitment status
    Study complete
    Actual primary completion date
    Not applicable
    Actual study completion date
    2015-02-03

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Participate in clinical trial
    Additional information
    Results for study 115775 can be found on the GSK Clinical Study Register.
    Click here
    Access to clinical trial data by researchers
    Visit website