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.

Pfizer

Status and phase: Completed; Phase 2

Conditions: Non-Alcoholic Fatty Liver Disease (NAFLD)

Treatments: Drug: PF-06865571 Monotherapy; Drug: Placebo; Drug: PF-05221304 Monotherapy; Drug: PF-05221304 and PF-06865571 Combination

Study type: Interventional

Funder types: Industry

Identifiers

NCT03776175

C3711001

Details and patient eligibility

About

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.

Enrollment: 99 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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99 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo (PF 05221304) BID Placebo (PF 06865571) BID

Treatment:

Drug: Placebo

PF-05221304 Monotherapy

Experimental group

Description:

15 mg PF-05221304 BID Placebo (PF-06865571) BID

Treatment:

Drug: PF-05221304 Monotherapy

Drug: Placebo

PF-06865571 Monotherapy

Experimental group

Description:

Placebo (PF-05221304) BID 300 mg PF-06865571 BID

Treatment:

Drug: Placebo

Drug: PF-06865571 Monotherapy

PF-05221304 and PF-06865571 Combination

Experimental group

Description:

15 mg PF-05221304 BID 300 mg PF-06865571 BID

Treatment:

Drug: PF-05221304 and PF-06865571 Combination

Drug: PF-05221304 Monotherapy

Drug: PF-06865571 Monotherapy