Pro-arrhythmic Potential of GSK3039294 in Healthy Subjects

This is an interventional treatment trial for Amyloidosis focused on measuring Pro-arrhythmic, Holter ECG, SAP, Cardiac telemetry, Benign arrhythmic Read More

Eligibility Criteria

Inclusion Criteria:

• 18 to 65 years of age inclusive at the time of signing the informed consent.
• Non-smokers only (defined as a non-smoker during the last 3 months prior to screening).
• Body weight > 50 kilograms and body mass index (BMI) and <=30 kilograms/meter square.
• Male subjects and women of non-child bearing potential only will be eligible.
• Male subjects with female partners of childbearing potential must comply with one of the following contraception requirements from the time of first dose of study medication until completion of the follow-up visit.
• Vasectomy with documentation of azoospermia.
• Male condom plus partner use of one of the contraceptive options: Contraceptive sub dermal implant that meets the effectiveness criteria of a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the standard operating procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Contraceptive vaginal ring; Occlusive cap (female diaphragm or cervical/vault cap) with a vaginal spermicide (foam, gel, cream or suppository).
• Capable of giving signed informed.
• 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 parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase and bilirubin <=1.5 ULN (Upper Limit of Normal) (isolated bilirubin >1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

Exclusion Criteria:

• History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
• Clinically significant blood pressure as determined by the investigator.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QT interval corrected for heart rate according to Fridericia's formula (QTcF)>450 milliseconds.
• Screening 12-lead ECG with any of the following: second/third degree atrioventricular block (AVB); significant pathological Q-waves (defined as Q-wave > 40 milliseconds or depth greater than 0.4-0.5 millivolts); ventricular pre-excitation; complete left bundle branch block (LBBB); bradycardia as defined by sinus rate <= 35 beats per minute (BPM).
• Any clinically relevant abnormality on the screening medical assessment laboratory examination or ECG.
• A personal history of corrected QT interval (QTc) prolongation, symptomatic cardiac arrhythmias or cardiac arrest.
• Sinus bradycardia <= 35 BPM or junctional arrhythmia > 60 BPM for 10 seconds or longer on run-in Holter or pre-dose inpatient telemetry.
• Non-sustained supraventricular tachycardia (NSVT) or more than 30 Ventricular Premature Depolarization (VPD)/hour on run-in Holter or pre-dose inpatient telemetry.
• Atrial tachycardia > 100 BPM for 3 seconds or longer or more than 40 Atrial Premature Depolarization (APD)/hour on run-in Holter or pre-dose inpatient telemetry.
• 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.
• Participation in the study would result in loss of blood or blood products in excess of 500 milliliters within 56-day period.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• 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).
• Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening.
• Positive Hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
• Positive pre-study drug/alcohol screen.
• Positive human immunodeficiency virus (HIV) antibody test.
• Regular use of known drugs of abuse.
• Regular alcohol consumption within six months prior to the study defined as: For United Kingdom (UK) sites an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (equivalent to 240 milliliters) of beer, one glass (125 milliliters) of wine or one (25 milliliters) measure of spirits.
• Urinary cotinine levels indicative of smoking/history/regular use of tobacco/nicotine-containing products within 3 months prior to screening.
• Sensitivity to heparin or heparin-induced thrombocytopenia.
• Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.