- Male subjects or female subjects of non childbearing potential
- Total body weight of >50 kg (110 lbs) and a BMI greater than or equal to 25 kg/m2
- Medical diagnosis of Type 2 Diabetes Mellitus (T2DM) being treated with no more than 1
acceptable oral antidiabetic drug OR Subjects without a diagnosis of T2DM that meet 2
or more of the following 5 criteria commonly associated with metabolic syndrome
- Fasting Plasma Glucose (FPG) greater than or equal to 100 mg/dL;
- Documentation of at least stage 1 hypertension or medical history of
hypertension;
- Fasting serum HDL C pharmacological agents with explicit purpose to increase HDL-C;
- Fasting serum triglyceride (TG) greater than or equal to 150 mg/dL or on
pharmacological agents with explicit purpose to decrease TG;
- Waist circumference greater than or equal to 40 inches (102 cm) for males and 35
inches (89 cm) for females.
- Liver fat greater than or equal to 8% measured by MRI PDFF
- Subjects with acute or chronic medical or psychiatric condition.
- Subjects with any of the following clinical laboratory abnormalities:
- Fasting TG >400 mg/dL;
- AST, ALT, or GGT >2.0x ULN;
- Hemoglobin A1c (HbA1c) >7.0%;
- Fasting plasma glucose >270 mg/dL;
- Total bilirubin >1.5x ULN;
- Albumin
- Platelet count
- International normalized ratio (INR) greater than or equal to 1.3.
- A positive urine test for illicit drugs.
- History of regular alcohol consumption.
- Seated systolic BP>=160 mmHg and/or diastolic BP>=100 mmHg.
- Supine 12 lead ECG demonstrating a corrected QT (QTcF) interval >450 msec or a QRS
interval >120 msec.
- Subjects with an estimated GFR
- Evidence or diagnosis of other forms of chronic liver diseases.
- Subjects with any of the following medical conditions:
- Any condition possibly affecting drug absorption (eg prior bariatric surgery,
gastrectomy, ileal resection);
- Diagnosis of type 1 diabetes mellitus;
- History of congestive heart failure, unstable angina, myocardial infarction,
stroke, or transient ischemic attack;
- Any malignancy not considered cured (except basal cell carcinoma and squamous
cell carcinoma of the skin);
- Active placement of medical devices in/on thoracic or abdominal cavities such as
pacemakers, defibrillators;
- Subjects with any anatomical or pathological abnormality that would either preclude or
tend to confound the analysis of study data.
- Blood donation of approximately 1 pint or more within 60 days prior to dosing.
- Subjects taking prohibited concomitant medication(s) or those unwilling/unable to
switch to permitted concomitant medication(s)
- Weight loss of greater than or equal to 5% within 1 month prior to Screening.
- Unwilling or unable to comply with the Lifestyle Requirements criteria of the
protocol.
- Pregnant female subjects; breastfeeding female subjects; female subjects of
childbearing potential; fertile male subjects who are unwilling or unable to use
highly effective method(s) of contraception.
- Investigator site staff members or Pfizer employees, including their family members,
directly involved in the conduct of the study.
- Subjects with known prior treatment with or participation in a clinical trial
involving any of the IPs