Phase 2a, Dose-ranging Study With PF-05221304 in Nonalcoholic Fatty Liver Disease (NAFLD)

Phase 2

Completed

Conditions: Nonalcoholic Fatty Liver Disease
Nonalcoholic Steatohepatitis

Interventions: Drug: Placebo
Drug: PF-05221304

Registration Number: NCT03248882

Lead Sponsor: Pfizer

Brief Summary: Phase 2a, dose-ranging Study with PF-05221304 in Nonalcoholic Fatty Liver Disease (NAFLD)

Detailed Description: A Phase 2a, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Parallel Group Study To Evaluate Safety, Tolerability, And Pharmacodynamics Of PF-05221304 Administered Daily For 16-weeks To Adult Subjects With Nonalcoholic Fatty Liver Disease

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 305

Inclusion Criteria

Body Mass Index >= 25 kg/m2
Body Weight > 50 kg
Liver fat (assessed via MRI-PDFF) >= 8%
Biopsy-proven NASH - diagnosed in previous 24-months
Presumed NASH - per Sponsor's definition
NAFLD with minimal inflammation/fibrosis
Features of Metabolic Syndrome

Exclusion Criteria

Alcohol-induced steatohepatitis or other forms of chronic liver disease
Positive for Hepatitis B, Hepatitis C, or Human Deficiency Virus
Severe Renal Impairment
Contraindications for MRI

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Double-Blind, PF-05221304-matching Placebo
PF-05221304 - 2 mg	PF-05221304	PF-05221304 - 2 mg, once-daily
PF-05221304 - 10 mg	PF-05221304	PF-05221304 - 10 mg, once-daily
PF-05221304 - 25 mg	PF-05221304	PF-05221304 - 25 mg, once-daily
PF-05221304 - 50 mg	PF-05221304	PF-05221304 - 50 mg, once-daily

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Liver Fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI- PDFF) at Week 16	Baseline (between Day -14 and Day 1), Week 16	MRI-PDFF utilized a gradient echo sequence with low flip angle (FA) to minimize T1 bias, corrected T2\* decay (due to iron overload) via modeling of the fat signal as a superposition of multiple frequency components from 5 different lipid types, and was applied in each of the 9 Couinaud segments. This technique improved fat quantification accuracy for the entire liver permitting quantification of small differences/changes following pharmacological intervention.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events	From first dose of study treatment (Day 1) up to Week 20	An AE was any untoward medical occurrence in a study subject administered a product or medical device. A serious AE (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent.
Percent Change From Baseline in Alanine Aminotransferase at Week 16	Baseline (Day 1 pre-dose), Week 16	Potential improvement in liver function was denoted by reduction in alanine transaminase (ALT)
Number of Participants With Laboratory Abnormalities	From first dose of study treatment (Day 1) up to Week 20	Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time \[PT\], PT/international normalized ratio, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin, granular casts).
Number of Participants With Vital Signs Data Meeting Predefined Criteria	From first dose of study treatment (Day 1) up to Week 18	Vital signs categorical summarization criteria: 1) sitting systolic blood pressure (SBP) \<90 or \>180 millimeters of mercury (mmHg); 2) sitting diastolic blood pressure (DBP) \<50 mmHg or \>110 mmHg; 3) sitting pulse rate \<40 or \>120 beats per minute (bpm); 4) change from baseline (increase or decrease) in sitting DBP greater than or equal to (\>=) 20 mmHg; 5) change from baseline (increase or decrease) in sitting SBP \>=30 mmHg.
Number of Participants With 12-Lead Electrocardiogram (ECG) Data Meeting Predefined Criteria	From first dose of study treatment (Day 1) up to Week 18	ECG categorical summarization criteria: 1) QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization) \>=140 milliseconds (msec); 2) QRS interval \>=50% change from baseline; 3) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization) \>=300 msec; 4) PR interval \>=25% change when baseline is \>200 msec or \>=50% change when baseline is \<=200 msec; 5) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of \>=500 msec; 6) QTcF interval (QT corrected for heart rate using Fridericia's formula) absolute value of 450 to \<480 msec; 7) QTcF interval: absolute value of 480 to \<500 msec; 8) QTcF interval: absolute value \>=500 msec; 9) QTcF interval: a change from baseline of 30 to \<60 msec; 10) QTcF interval: a change from baseline \>=60 msec.

Trial Locations

Locations (137): Franco Felizarta MD
🇺🇸
Bakersfield, California, United States
eStudySite
🇺🇸
La Mesa, California, United States
San Diego Imaging Chula Vista
🇺🇸
Chula Vista, California, United States
University of California, San Diego (Altman Clinical and Translational Research Institute)
🇺🇸
La Jolla, California, United States
University of California, San Diego
🇺🇸
La Jolla, California, United States
Clinical Trials Research
🇺🇸
Lincoln, California, United States
National Research Institute
🇺🇸
Los Angeles, California, United States
Stanford University Medical Center, Blake wilbur Building
🇺🇸
Palo Alto, California, United States
Stanford University Medical Center
🇺🇸
Palo Alto, California, United States
Huntington Medical Research Institute
🇺🇸
Pasadena, California, United States
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Franco Felizarta MD
🇺🇸Bakersfield, California, United States