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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03248882
Recruitment Status : Completed
First Posted : August 14, 2017
Results First Posted : March 10, 2020
Last Update Posted : March 10, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

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

Condition or disease Intervention/treatment Phase
Nonalcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis Drug: Placebo Drug: PF-05221304 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 305 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: C1171002 is a randomized, double blind, placebo controlled, 5 arm (placebo, plus 4 active doses of PF 05221304), parallel group study.
Masking: Double (Participant, Investigator)
Masking Description: Double-Blind
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 22, 2017
Actual Primary Completion Date : February 26, 2019
Actual Study Completion Date : March 27, 2019


Arm Intervention/treatment
Placebo Comparator: Placebo
Double-Blind, PF-05221304-matching Placebo
Drug: Placebo
Placebo

Active Comparator: PF-05221304 - 2 mg
PF-05221304 - 2 mg, once-daily
Drug: PF-05221304
PF-05221304, Experimental Drug

Active Comparator: PF-05221304 - 10 mg
PF-05221304 - 10 mg, once-daily
Drug: PF-05221304
PF-05221304, Experimental Drug

Active Comparator: PF-05221304 - 25 mg
PF-05221304 - 25 mg, once-daily
Drug: PF-05221304
PF-05221304, Experimental Drug

Active Comparator: PF-05221304 - 50 mg
PF-05221304 - 50 mg, once-daily
Drug: PF-05221304
PF-05221304, Experimental Drug




Primary Outcome Measures :
  1. Percent Change From Baseline in Liver Fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI- PDFF) at Week 16 [ Time Frame: 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 :
  1. Percent Change From Baseline in Alanine Aminotransferase at Week 16 [ Time Frame: Baseline (Day 1 pre-dose), Week 16 ]
    Potential improvement in liver function was denoted by reduction in alanine transaminase (ALT)

  2. Number of Participants With Treatment-Emergent Adverse Events [ Time Frame: 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.

  3. Number of Participants With Laboratory Abnormalities [ Time Frame: 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).

  4. Number of Participants With Vital Signs Data Meeting Predefined Criteria [ Time Frame: 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.

  5. Number of Participants With 12-Lead Electrocardiogram (ECG) Data Meeting Predefined Criteria [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03248882


Locations
Show Show 140 study locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] October 3, 2017
Statistical Analysis Plan  [PDF] March 14, 2019

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03248882    
Other Study ID Numbers: C1171002
2017-001156-55 ( EudraCT Number )
First Posted: August 14, 2017    Key Record Dates
Results First Posted: March 10, 2020
Last Update Posted: March 10, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
PF-05221304
NAFLD
NASH
features of metabolic syndrome
Dose-Ranging Study
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases