A Study To Assess Pharmacodynamics, Safety And Tolerability Of PF-05221304 And PF-06865571 Co-Administered For 6 Weeks In Adults With Non-Alcoholic Fatty Liver Disease.

This is an interventional treatment trial for Non-Alcoholic Fatty Liver Disease (NAFLD) Read More

Inclusion Criteria:

• 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 <40 mg/dL for males and <50 mg/dL for females, or on 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

Exclusion Criteria:

• 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 < lower limit of normal (LLN);
  • Platelet count <0.95x LLN;
  • 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 <60 mL/min/1.73m2.
• 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