- 1. Healthy male and/or female subjects of non child bearing potential who, at the time
of screening, are between the ages of 18 and 55 years, inclusive. Healthy is defined
as no clinically relevant abnormalities identified by a detailed medical history, full
physical examination, including blood pressure and pulse rate measurement, 12 lead ECG
or clinical laboratory tests.
Female subjects of nonchildbearing potential must meet at least 1 of the following
criteria:
1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at
least 12 consecutive months with no alternative pathological or physiological cause;
with a serum follicle stimulating hormone (FSH) level confirming the postmenopausal
state;
2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
3. Have medically confirmed ovarian failure. All other female subjects (including females
with tubal ligations and females that do NOT have a documented hysterectomy, bilateral
oophorectomy and/or ovarian failure) are considered to be of childbearing potential.
2. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110
lb).
3. Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the study.
4. Subjects who are willing and able to comply with all scheduled visits, treatment
plan, laboratory tests, and other study procedures.
- Screening supine 12 lead ECG demonstrating a corrected QT (QTc) interval >450
msec or a QRS interval >120 msec. If QTc exceeds 450 msec, or QRS exceeds 120
msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS
values should be used to determine the subject's eligibility.
Subjects with family history of myocardial infarction, congenital long QT syndrome,
torsades de pointes or clinically significant ventricular arrhythmias. Subjects should
be within normal range of potassium, magnesium and corrected calcium calculation at
screening.
Pregnant female subjects; breastfeeding female subjects; female subjects of
childbearing potential; male subjects with partners currently pregnant; male subjects
who are unwilling or unable to use atleast one highly effective methods of
contraception as outlined in this protocol for the duration of the study and for at
least 90 days after the last dose of investigational product and, refrain from sperm
donation for the duration of the Study and for at least 90 days after the last dose of
investigational product.
History of known QTc prolongation or ECG abnormalities.
Self-reported history of risk factors for QT prolongation or torsades de pointes (eg,
organic heart disease, congestive heart failure, hypokalemia,
hypomagnesemia,congenital long QT syndrome, myocardial ischemia or infarction,
congenital deafness, and family history of sudden death, or a family history of
congenital QT syndrome).
Self-reported history of sick sinus syndrome, first, second, or third degree
atrioventricular (AV) block, myocardial infarction, pulmonary congestion, cardiac
arrhythmia, prolonged QT interval or conduction abnormalities, or any other clinically
significant cardiovascular disease history..