CiPA Phase 1 ECG Biomarker Validation Study

Inclusion criteria

• Subject signs an institutional review board (IRB) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] authorization) before any study related procedures are performed.
• Subject is a healthy man or woman, 18 to 50 years of age, inclusive, who weighs at least 50 kg (110 pounds) and has a body mass index of 18 to 30 kg/m2, inclusive, at Screening.
• Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead ECG results, and physical examination findings at Screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
• Female subjects will be at least 2 years postmenopausal, surgically sterile, or practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique).
• Female subjects must not be pregnant or lactating before enrollment in the study.
• Male or female subjects must agree to practice 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from Screening until 30 days after the last dose of study drug.
• Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study.

Exclusion criteria

• Subject has a safety 12 lead ECG result at Screening or Check in with evidence of any of the following abnormalities:
• QTc using Fridericia correction (QTcF) >430 msec
• PR interval >220 msec or 110 msec
• Second- or third-degree atrioventricular block
• Complete left or right bundle branch block or incomplete right bundle branch block
• Heart rate 90 beats per minute
• Pathological Q-waves (defined as Q wave >40 msec)
• Ventricular pre-excitation
• Subject has more than 12 ectopic beats during the 3 hour Holter ECG at Screening.
• Subject has a history of unexplained syncope, structural heart disease, long QT syndrome, heart failure, myocardial infarction, angina, unexplained cardiac arrhythmia, torsade de pointes, ventricular tachycardia, or placement of a pacemaker or implantable defibrillator. Subjects will also be excluded if there is a family history of long QT syndrome (genetically proven or suggested by sudden death of a close relative due to cardiac causes at a young age) or Brugada syndrome.
• Subject has a history or current evidence of any clinically significant (as determined by the investigator) cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, neurologic, psychiatric, pulmonary, renal, urologic, and/or other major disease or malignancy (excluding nonmelanoma skin cancer). The investigator may allow exceptions to these criteria (e.g., cholecystectomy, childhood asthma) following discussion with the medical monitor.
• Subject has a history of thoracic surgery.
• Subject has any condition possibly affecting study drug absorption (e.g., gastrectomy, Crohn's disease, irritable bowel syndrome).
• Subject has a skin condition likely to compromise ECG electrode placement.
• Subject is a female with breast implants.
• Subject's laboratory test results at Screening or Check in are outside the reference ranges provided by the clinical laboratory and considered clinically significant (as determined and documented by the investigator or designee).
• Subject's laboratory test results at Screening or Check in indicate hypokalemia, hypocalcemia, or hypomagnesemia according to lower limits of the reference ranges provided by the clinical laboratory.
• Subject's laboratory test results at Screening or Check in are >2 × the upper limit of normal (ULN) for alanine aminotransferase or aspartate aminotransferase, >1.5 × ULN for bilirubin, or >1.5 × ULN for creatinine.
• Subject