A Randomized, Three Period Crossover Thorough QT (TQT) Study Evaluating the Effect of ETX2514 on Cardiac Repolarization in Healthy Male or Female Volunteers
A Randomized, Three Period Crossover Thorough QT (TQT) Study Evaluating the Effect of ETX2514 on Cardiac Repolarization in Healthy Male or Female Volunteers
This study is being conducted to evaluate the effects of supratherapeutic ETX2514 plasma concentrations on the heart rate-corrected QT interval (QTc).
Inclusion Criteria:
Healthy, adult, male or female, 18-55 years of age, inclusive, at Screening
Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose
Must weigh at least 60 kilograms (kg) for males or 52 kg for females and have a body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/meters squared (m^2) at Screening.
Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Principal Investigator (PI)
Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must have a negative serum pregnancy test before randomization. Participating heterosexual women of childbearing potential must be willing to consistently use 2 highly effective methods of contraception (i.e., condom with spermicide, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from Screening until at least 30 days after administration of the last dose of study drug; and
Non-childbearing women must have had a hysterectomy, surgical sterilization, or be postmenopausal at least 12 months prior to Screening.
Male participants must be willing to use condoms with spermicide during sexual intercourse from Screening until at least 90 days after administration of the last dose of study drug.
Male participants with a vasectomy must have had the vasectomy at least 90 days prior to randomization.
Male participants must agree not to donate sperm from the Screening period through 90 days after the last dose.
Understands the study procedures in the informed consent form and is willing and able to comply with the protocol
Able to swallow tablets
Supine blood pressure between 90/40 millimeters of mercury (mmHg) and 140/90 mmHg (inclusive) at Screening
No clinically significant history or presence of ECG findings as judged by the PI at Screening and check-in, including each criterion as listed below:
Has serum potassium, calcium, and magnesium levels within the normal range at Screening
Exclusion Criteria:
Participant is mentally or legally incapacitated or has significant emotional problems at the time of the Screening visit or expected during the conduct of the study.
History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI
History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the participant by their participation in the study
History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose of study drug
History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, related compounds, or inactive ingredients
History of significant multiple and/or severe allergies (e.g., latex allergy, band aids, adhesive dressing, or medical tape), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs
Female participants who are pregnant or lactating
Positive urine drug or alcohol results at Screening or check-in
Positive results at Screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV)
Unable to refrain from or anticipates the use of:
Has been on a diet incompatible with the on-study diet (including an extreme diet which resulted in a significant weight change for whatever reason), in the opinion of the PI, within the 28 days prior to the first dose of study drug, and throughout the study
Donation of blood or significant blood loss more than 500 milliliters (mL) within 56 days prior to the first dose of study drug
Plasma donation within 7 days prior to the first dose of study drug
Has had surgery or any medical condition which may affect the absorption, distribution, metabolism, or elimination of the study drug within 6 months prior to the first dose, in the opinion of the PI
Participation in another clinical trial within 28 days prior to the first dose of study drug. The 28-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study.
Participation in a previous clinical trial where participant received ETX2514
History or presence of:
hypokalemia, in the opinion of the PI;
risk factors for Torsades de Pointes (e.g., heart failure, cardiomyopathy, or family history of Long QT Syndrome);
sick sinus syndrome, second- or third-degree atrioventricular block, pulmonary congestion, cardiac arrhythmia, prolonged QT interval, or conduction abnormalities;
repeated or frequent vasovagal episodes:
Participant has a history within the last 6 months of frequent strenuous exercise, and/or is unwilling to refrain from strenuous exercise from 7 days prior to baseline Day -1 through the last Follow-Up Visit.
Participants who refused to abstain from caffeine-containing foods or caffeinated beverages (e.g., coffee, tea, cola, energy drinks) for 7 days prior to Day -1 through the last Follow-up Visit
Participants who refused to abstain from alcohol from 7 days prior to Day -1 through the last Follow-Up Visit
Participants who refused to abstain from grapefruit-containing foods or beverages or Seville orange-containing foods or beverages from 2 weeks prior to Day -1 through the last Follow-Up Visit
Participant has consumed cruciferous vegetables (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard greens) or charbroiled meats within 7 days prior to check-in through the last Follow-up Visit