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.
Condition: Non-Alcoholic Fatty Liver Disease (NAFLD)
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: PF-05221304 Monotherapy; PF-06865571 Monotherapy; Placebo; PF-05221304 and PF-06865571 Combination
Intervention description: Participants enrolled in this Arm will receive 15 mg dose of PF-05221304 (3 tablets of 5 mg each) and 3 tablets of Placebo for PF-06865571, each to be taken twice daily for 41 days and once on Day 42.; Participants enrolled in this Arm will receive 300 mg dose of PF-06865571 (3 tablets of 100 mg each) and 3 tablets of Placebo for PF-05221304, all to be taken twice daily for 41 days and once on Day 42.; Participants enrolled in this Arm will receive 3 tablets for Placebo of PF-05221304 and 3 tablets of Placebo of PF-06865571, to be taken twice daily for 41 days and once on Day 42.; Participants enrolled in this Arm will receive 15 mg dose of PF-05221304 (3 tablets of 5 mg each) and 3 tablets of PF-06865571 (3 tablets of 100 mg each), each to be taken twice daily for 41 days and once on Day 42.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 99.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This study is to assess the effect of PF 05221304 alone, PF 06865571 alone, the co
      administration of PF 05221304 and PF 06865571, or placebo on whole liver fat in subjects with
      NAFLD. In addition, this study will evaluate the safety and tolerability of co administration
      of PF 05221304 and PF 06865571 along with the effects on selected pharmacodynamics
      (PD)/exploratory parameters, compared to administration of PF 05221304 alone, PF 06865571
      alone, and placebo in adults with NAFLD.
    

Eligibility criteria:

        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