Phase 2a, Dose-ranging Study With PF-05221304 in Nonalcoholic Fatty Liver Disease (NAFLD)
- Conditions
- Nonalcoholic Fatty Liver DiseaseNonalcoholic Steatohepatitis
- Interventions
- Drug: Placebo
- 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
- 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
- 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)
Discovery Clinical Services Ltd.
🇨🇦Victoria, British Columbia, Canada
South Denver Gastroenterology, P.C.
🇺🇸Englewood, Colorado, United States
ClinSearch
🇺🇸Chattanooga, Tennessee, United States
Oxford Medical Imaging
🇨🇦Mississauga, Ontario, Canada
Digestive Disease Associates, PA
🇺🇸Catonsville, Maryland, United States
Krakowskie Centrum Medyczne sp. z o.o.
🇵🇱Krakow, Poland
Schiff Center for Liver Diseases/University of Miami
🇺🇸Miami, Florida, United States
Stand Up MRI of Miami
🇺🇸Miami, Florida, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Midwest Institute for Clinical Research
🇺🇸Indianapolis, Indiana, United States
Precision Research Institute
🇺🇸San Diego, California, United States
Sterling Research Group, Ltd.
🇺🇸Cincinnati, Ohio, United States
Holy Family Hospital
🇮🇱Nazareth, Israel
Independent Imaging
🇺🇸Wellington, Florida, United States
Franco Felizarta MD
🇺🇸Bakersfield, California, United States
University of California, San Diego
🇺🇸La Jolla, California, United States
Dr. Jones & Partners Medical Imaging
🇦🇺Adelaide, South Australia, Australia
IRM Quebec
🇨🇦Quebec, Canada
Storr Liver Centre, Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Rabin Medical Center
🇮🇱Petah Tikva, Israel
Gabinet Lekarski Malgorzata Saryusz-Wolska
🇵🇱Lodz, Poland
Quest Clinical Research
🇺🇸San Francisco, California, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Clinical Trials of Texas, Inc.
🇺🇸San Antonio, Texas, United States
Pinnacle Clinical Research, PLLC
🇺🇸San Antonio, Texas, United States
St. Joseph's Health Care London
🇨🇦London, Ontario, Canada
St. Michael's Hospital - MRI Research Centre
🇨🇦Toronto, Ontario, Canada
Toronto Liver Centre - Liver Care Centre Corporation
🇨🇦Toronto, Ontario, Canada
Resonance Magnetique du Saguenay-Lac-Saint-Jean
🇨🇦Chicoutimi, Quebec, Canada
Medpharmgene Inc
🇨🇦Montreal, Quebec, Canada
Radiologie Varad
🇨🇦Montreal, Quebec, Canada
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Flinders Medical Centre/Department of Gastroenterology & Hepatology
🇦🇺Adelaide, South Australia, Australia
eStudySite
🇺🇸La Mesa, California, United States
Clinical Trials Research
🇺🇸Lincoln, California, United States
San Diego Imaging Chula Vista
🇺🇸Chula Vista, California, United States
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
Jacksonville Center for Clinical Research
🇺🇸Jacksonville, Florida, United States
Avail Clinical Research, LLC
🇺🇸Orange City, Florida, United States
Heartland Research Associates, LLC
🇺🇸Wichita, Kansas, United States
Ascension Via Christi Imaging at St. Francis
🇺🇸Wichita, Kansas, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Wake Research Associates, LLC
🇺🇸Raleigh, North Carolina, United States
PMG Research of Wilmington, LLC
🇺🇸Wilmington, North Carolina, United States
Baylor College of Medicine - Advanced Liver Therapies
🇺🇸Houston, Texas, United States
Pinnacle Clinical Research
🇺🇸Rollingwood, Texas, United States
Clinical Research Advantage, Inc./Wasatch Peak Family Practice
🇺🇸Layton, Utah, United States
Australian Clinical Research Network
🇦🇺Maroubra, New South Wales, Australia
Spectrum Medical Imaging
🇦🇺Randwick, New South Wales, Australia
Castlereagh Imaging
🇦🇺Westmead, New South Wales, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Radiology SA
🇦🇺Adelaide, South Australia, Australia
False Creek Healthcare
🇨🇦Vancouver, British Columbia, Canada
Nova Scotia Health Authority, QEII Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
LMC Clinical Research Inc. (Bayview)
🇨🇦Toronto, Ontario, Canada
Aggarwal and Associates Limited
🇨🇦Brampton, Ontario, Canada
London Health Sciences Centre - University Hospital
🇨🇦London, Ontario, Canada
Nova Scotia Health Authority - QEII Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
University Health Network (UHN)
🇨🇦Toronto, Ontario, Canada
Ecogene-21
🇨🇦Chicoutimi, Quebec, Canada
Clinique de Medecine Urbaine du Quartier Latin
🇨🇦Montreal, Quebec, Canada
Centre de recherche du CHUM
🇨🇦Montreal, Quebec, Canada
Chronic Viral Illness Service - Royal Victoria Hospital - McGill University Health Centre (MUHC)
🇨🇦Montreal, Quebec, Canada
Cedar Cancer Center - McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Research Institute of the MUHC
🇨🇦Montreal, Quebec, Canada
Recherche Medicale St-Jerome Inc
🇨🇦St-Jerome, Quebec, Canada
Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Estrie
🇨🇦Sherbrooke, Quebec, Canada
Centre de recherche de l'Institut Universitaire de Cardiologie et de pneumologie de Quebec
🇨🇦Quebec, Canada
Centre de recherche Saint-Louis
🇨🇦Quebec, Canada
IRM Québec - Clinique St-Louis
🇨🇦Quebec, Canada
CHU de Quebec - Universite Laval - site Centre Hospitalier de l'Universite Laval (CHUL)
🇨🇦Quebec, Canada
Hillel Yaffe Medical Center
🇮🇱Hadera, Israel
Rambam Health Care Campus
🇮🇱Haifa, Israel
Alpha Recherche Clinique
🇨🇦Quebec, Canada
Clinix
🇨🇦Quebec, Canada
Hadassah Hebrew University Medical Center - Ein Kerem
🇮🇱Jerusalem, Israel
The Chaim Sheba Medical Center
🇮🇱Ramat-Gan, Israel
Galilee Medical Center
🇮🇱Nahariya, Israel
Tel-Aviv Sourasky Medical Center
🇮🇱Tel-Aviv, Israel
Synexus Polska Sp. z o.o. Oddzial w Gdyni
🇵🇱Gdynia, Poland
Osrodek Badan Klinicznych
🇵🇱Jaworze, Poland
Synexus Polska Sp. z o.o. Oddzial w Katowicach
🇵🇱Katowice, Poland
Centrum Medyczne A-Z Clinic
🇵🇱Krakow, Poland
Centrum Medyczne Medyk
🇵🇱Rzeszow, Poland
Synexus Polska Sp. z o.o. Oddzial we Wroclawiu
🇵🇱Wroclaw, Poland
Niepubliczny Zaklad Opieki Zdrowotnej Centrum Badan Klinicznych
🇵🇱Wroclaw, Poland
DOBROSTAN - Gabinety Lekarskie
🇵🇱Wroclaw, Poland
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Changhua Christian Hospital
🇨🇳Changhua city, Changhua County, Taiwan
Qps-Mra, Llc
🇺🇸South Miami, Florida, United States
University of California, San Diego (Altman Clinical and Translational Research Institute)
🇺🇸La Jolla, California, United States
National Research Institute
🇺🇸Los Angeles, California, United States
Ocean Blue Medical Research Center, Inc
🇺🇸Miami Springs, Florida, United States
BioTelemetry Research
🇺🇸Rochester, New York, United States
Stanford University Medical Center, Blake wilbur Building
🇺🇸Palo Alto, California, United States
Huntington Medical Research Institute
🇺🇸Pasadena, California, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Gastrointestinal Associates, PA
🇺🇸Flowood, Mississippi, United States
Borland-Groover Clinic
🇺🇸Jacksonville, Florida, United States
Advanced Gastroenterology Associates, LLC
🇺🇸Palm Harbor, Florida, United States
South Florida Center Of Gastroenterology, PA
🇺🇸Wellington, Florida, United States
Colonnades at Baptist
🇺🇸Jackson, Mississippi, United States
Prime Imaging (Chattanooga Outpatient Center)
🇺🇸Chattanooga, Tennessee, United States
Royal Adelaide Hospital, Department of Gastroenterology and Hepatology
🇦🇺Adelaide, South Australia, Australia
University Health Network (UHN) - Toronto General Hospital - Toronto Centre for Liver Disease (TCLD)
🇨🇦Toronto, Ontario, Canada
University of Toronto - Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Tampa General Medical Group
🇺🇸Tampa, Florida, United States
Invision Imaging
🇺🇸Honolulu, Hawaii, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Centrum Badan Klinicznych PI-House Sp. z o.o.
🇵🇱Gdansk, Poland
Synexus Polska Sp. z o. o. Oddzial w Warszawie
🇵🇱Warszawa, Poland
National Cheng-Kung University Hospital
🇨🇳Tainan, Taiwan
Synexus Polska Sp. z o.o. Oddzial w Gdansku
🇵🇱Gdansk, Poland
Silmedic Sp. z o.o. Oddzial w Katowicach
🇵🇱Katowice, Poland
Synexus Polska Sp. z o.o Oddzial w Poznaniu
🇵🇱Poznan, Poland
False Creek Healthcare Centre
🇨🇦Vancouver, British Columbia, Canada
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
ClinicMed Badurski i wspolnicy Spolka Jawna
🇵🇱Bialystok, Poland
Chung-Ho Memorial Hospital, Kaohsiung Medical University
🇨🇳Kaohsiung, Taiwan
LAIR Centre
🇨🇦Vancouver, British Columbia, Canada
West Coast Medical Imaging
🇨🇦Victoria, British Columbia, Canada
Dr TG Elliott Inc - BC Diabetes
🇨🇦Vancouver, British Columbia, Canada
Bioclinica Research
🇺🇸Orlando, Florida, United States
East-West Medical Research Institute
🇺🇸Honolulu, Hawaii, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
University of South Florida
🇺🇸Tampa, Florida, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
The University of North Carolina at Chapel Hill, Biomedical Research Imaging Center (MRI Facility)
🇺🇸Chapel Hill, North Carolina, United States
PMG Research, Inc.
🇺🇸Winston-Salem, North Carolina, United States
Touchstone
🇺🇸Austin, Texas, United States
Mayo Clinic- Main Campus
🇺🇸Rochester, Minnesota, United States
Investigational Drug Service, University of North Carolina Hospitals
🇺🇸Chapel Hill, North Carolina, United States
The University of NC at Chapel Hill, Clinical and Translational Research Center (CTRC)
🇺🇸Chapel Hill, North Carolina, United States
National Clinical Research - Richmond, Inc.
🇺🇸Richmond, Virginia, United States