A PHASE 2A, RANDOMIZED, DOUBLE BLIND (SPONSOR-OPEN), PLACEBO CONTROLLED, PARALLEL GROUP STUDY TO ASSESS THE PHARMACODYNAMICS, SAFETY AND TOLERABILITY OF PF-05221304 AND PF-06865571 CO-ADMINISTERED FOR 6 WEEKS IN ADULTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 99
- 试验地点
- 29
- 主要终点
- Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
- •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/1.73m
- •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
研究组 & 干预措施
Placebo
Placebo (PF 05221304) BID Placebo (PF 06865571) BID
干预措施: Placebo (Drug)
PF-05221304 Monotherapy
15 mg PF-05221304 BID Placebo (PF-06865571) BID
干预措施: PF-05221304 Monotherapy (Drug)
PF-05221304 Monotherapy
15 mg PF-05221304 BID Placebo (PF-06865571) BID
干预措施: Placebo (Drug)
PF-06865571 Monotherapy
Placebo (PF-05221304) BID 300 mg PF-06865571 BID
干预措施: PF-06865571 Monotherapy (Drug)
PF-06865571 Monotherapy
Placebo (PF-05221304) BID 300 mg PF-06865571 BID
干预措施: Placebo (Drug)
PF-05221304 and PF-06865571 Combination
15 mg PF-05221304 BID 300 mg PF-06865571 BID
干预措施: PF-05221304 Monotherapy (Drug)
PF-05221304 and PF-06865571 Combination
15 mg PF-05221304 BID 300 mg PF-06865571 BID
干预措施: PF-06865571 Monotherapy (Drug)
PF-05221304 and PF-06865571 Combination
15 mg PF-05221304 BID 300 mg PF-06865571 BID
干预措施: PF-05221304 and PF-06865571 Combination (Drug)
结局指标
主要结局
Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42
时间窗: Baseline, Day 42
Magnetic resonance imaging proton density fat fraction (MRI-PDFF) technique is an established method that enables quantification of fat content in the liver. It measures the fraction of mobile protons in the liver attributable to fat content and provides whole liver coverage so that fat content can be assessed across 8 Couinaud liver segments. Whole liver PDFF = PDFFs for (Segment I + Segment II + Segment III + Segment IVa + Segment IVb + Segment V + Segment VI + Segment VII + Segment VIII) divided by total number of segments assessed.
次要结局
- Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to 35 days from last dose of study drug or early termination: (maximum up to Day 77))
- Number of Participants With Laboratory Abnormalities(Baseline up to 35 days last from dose of study drug or early termination (maximum up to Day 77))
- Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure(Baseline, Post-last dose of study drug (up to Day 42))
- Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate(Baseline, Post- last dose of study drug (up to Day 42))
- Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria(Baseline up to 35 days last dose of study drug or early termination (maximum up to Day 77))