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NCT03248882

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

Completed Phase 2 Results posted Last updated 9 December 2020
What this trial tests

Phase 2 trial testing Placebo in Nonalcoholic Fatty Liver Disease in 305 participants. Completed in 27 March 2019.

Timeline
22 August 2017
Primary endpoint
26 February 2019
27 March 2019

Quick facts

Lead sponsorPfizer
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment305
Start date22 August 2017
Primary completion26 February 2019
Estimated completion27 March 2019
Sites140 locations across Taiwan, Israel, Poland, Canada, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

Adults 18 to 70, any sex, with Nonalcoholic Fatty Liver Disease or Nonalcoholic Steatohepatitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change From Baseline in Liver Fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI- PDFF) at Week 16 Primary · 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.

GroupValue95% CI
Placebo-7.2-13.9 – 0.0
PF-05221304 2 mg-17.1-22.7 – -11.1
PF-05221304 10 mg-49.9-53.3 – -46.2
PF-05221304 25 mg-55.9-59.0 – -52.4
PF-05221304 50 mg-64.8-67.5 – -62.0
Percent Change From Baseline in Alanine Aminotransferase at Week 16 Secondary · Baseline (Day 1 pre-dose), Week 16

Potential improvement in liver function was denoted by reduction in alanine transaminase (ALT)

GroupValue95% CI
Placebo-8.5-15.2 – -1.2
PF-05221304 2 mg-12.5-18.7 – -5.8
PF-05221304 10 mg-27.7-32.9 – -22.2
PF-05221304 25 mg-31.3-36.6 – -25.5
PF-05221304 50 mg-46.8-50.8 – -42.4
Number of Participants With Treatment-Emergent Adverse Events Secondary · 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.

All-causality AE
GroupValue95% CI
Placebo41
PF-05221304 2 mg40
PF-05221304 10 mg42
PF-05221304 25 mg45
PF-05221304 50 mg40
All-causality SAE
GroupValue95% CI
Placebo0
PF-05221304 2 mg1
PF-05221304 10 mg1
PF-05221304 25 mg2
PF-05221304 50 mg2
Treatment-related AE
GroupValue95% CI
Placebo16
PF-05221304 2 mg9
PF-05221304 10 mg12
PF-05221304 25 mg16
PF-05221304 50 mg23
Treatment-related SAE
GroupValue95% CI
Placebo0
PF-05221304 2 mg0
PF-05221304 10 mg0
PF-05221304 25 mg0
PF-05221304 50 mg0
Number of Participants With Laboratory Abnormalities Secondary · 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

GroupValue95% CI
Placebo39
PF-05221304 2 mg44
PF-05221304 10 mg36
PF-05221304 25 mg33
PF-05221304 50 mg40
Number of Participants With Vital Signs Data Meeting Predefined Criteria Secondary · 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.

Sitting SBP <90 mmHg
GroupValue95% CI
Placebo0
PF-05221304 2 mg0
PF-05221304 10 mg0
PF-05221304 25 mg0
PF-05221304 50 mg2
Sitting SBP >180 mmHg
GroupValue95% CI
Placebo0
PF-05221304 2 mg0
PF-05221304 10 mg0
PF-05221304 25 mg1
PF-05221304 50 mg0
Sitting SBP increase >=30 mmHg
GroupValue95% CI
Placebo5
PF-05221304 2 mg6
PF-05221304 10 mg2
PF-05221304 25 mg2
PF-05221304 50 mg0
Sitting SBP decrease >=30 mmHg
GroupValue95% CI
Placebo2
PF-05221304 2 mg1
PF-05221304 10 mg5
PF-05221304 25 mg7
PF-05221304 50 mg6
Sitting DBP <50 mmHg
GroupValue95% CI
Placebo1
PF-05221304 2 mg0
PF-05221304 10 mg0
PF-05221304 25 mg0
PF-05221304 50 mg0
Sitting DBP >110 mmHg
GroupValue95% CI
Placebo0
PF-05221304 2 mg0
PF-05221304 10 mg0
PF-05221304 25 mg0
PF-05221304 50 mg1
Sitting DBP increase >=20 mmHg
GroupValue95% CI
Placebo1
PF-05221304 2 mg4
PF-05221304 10 mg2
PF-05221304 25 mg2
PF-05221304 50 mg3
Sitting DBP decrease >=20 mmHg
GroupValue95% CI
Placebo0
PF-05221304 2 mg4
PF-05221304 10 mg3
PF-05221304 25 mg4
PF-05221304 50 mg4
Number of Participants With 12-Lead Electrocardiogram (ECG) Data Meeting Predefined Criteria Secondary · 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

PR interval >=300 msec
GroupValue95% CI
Placebo0
PF-05221304 2 mg0
PF-05221304 10 mg0
PF-05221304 25 mg0
PF-05221304 50 mg0
%Change in PR interval >=25/50%
GroupValue95% CI
Placebo0
PF-05221304 2 mg1
PF-05221304 10 mg0
PF-05221304 25 mg1
PF-05221304 50 mg1
QRS interval >=140 msec
GroupValue95% CI
Placebo0
PF-05221304 2 mg0
PF-05221304 10 mg1
PF-05221304 25 mg0
PF-05221304 50 mg0
%Change in QRS interval >=50%
GroupValue95% CI
Placebo0
PF-05221304 2 mg0
PF-05221304 10 mg0
PF-05221304 25 mg0
PF-05221304 50 mg0
QT interval >=500 msec
GroupValue95% CI
Placebo0
PF-05221304 2 mg0
PF-05221304 10 mg0
PF-05221304 25 mg1
PF-05221304 50 mg0
QTcF interval >=450 to <480 msec
GroupValue95% CI
Placebo6
PF-05221304 2 mg10
PF-05221304 10 mg7
PF-05221304 25 mg9
PF-05221304 50 mg3
QTcF interval >=480 to <500 msec
GroupValue95% CI
Placebo0
PF-05221304 2 mg1
PF-05221304 10 mg0
PF-05221304 25 mg1
PF-05221304 50 mg1
QTcF interval >=500 msec
GroupValue95% CI
Placebo0
PF-05221304 2 mg0
PF-05221304 10 mg0
PF-05221304 25 mg0
PF-05221304 50 mg0

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study treatment up to 20 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 0/61 (0%)
Deaths: 0/61
PF-05221304 2 mg
Serious: 1/63 (2%)
Deaths: 0/63
PF-05221304 10 mg
Serious: 1/62 (2%)
Deaths: 0/62
PF-05221304 25 mg
Serious: 2/58 (3%)
Deaths: 0/58
PF-05221304 50 mg
Serious: 2/61 (3%)
Deaths: 0/61

Serious adverse events (8 terms)

ReactionSystemPlaceboPF-05221304 2 mgPF-05221304 10 mgPF-05221304 25 mgPF-05221304 50 mg
Angina unstableCardiac disorders
Myocardial infarctionCardiac disorders
Myocardial ischaemiaCardiac disorders
PneumoniaInfections and infestations
Upper respiratory tract infectionInfections and infestations
Rib fractureInjury, poisoning and procedural complications
Renal colicRenal and urinary disorders
AsthmaRespiratory, thoracic and mediastinal disorders
Other adverse events (15 terms — click to expand)

ReactionSystemPlaceboPF-05221304 2 mgPF-05221304 10 mgPF-05221304 25 mgPF-05221304 50 mg
HypertriglyceridaemiaMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
HeadacheNervous system disorders
Abdominal pain upperGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
NauseaGastrointestinal disorders
FatigueGeneral disorders
Urinary tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
NasopharyngitisInfections and infestations
Blood triglycerides increasedInvestigations
PruritusSkin and subcutaneous tissue disorders

Most-reported serious reactions: Angina unstable, Myocardial infarction, Myocardial ischaemia, Pneumonia, Upper respiratory tract infection, Rib fracture, Renal colic, Asthma.

Data from ClinicalTrials.gov NCT03248882 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Mechanisms of NAFLD development and therapeutic strategies.
    Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. · · 2018 · cited 3203× · PMID 29967350 · DOI 10.1038/s41591-018-0104-9
  2. Targeting cancer metabolism in the era of precision oncology.
    Stine ZE, Schug ZT, Salvino JM, Dang CV. · · 2022 · cited 839× · PMID 34862480 · DOI 10.1038/s41573-021-00339-6
  3. Tumor biomarkers for diagnosis, prognosis and targeted therapy.
    Zhou Y, Tao L, Qiu J, Xu J, et al · · 2024 · cited 379× · PMID 38763973 · DOI 10.1038/s41392-024-01823-2
  4. Targeting fibrosis, mechanisms and cilinical trials.
    Zhao M, Wang L, Wang M, Zhou S, et al · · 2022 · cited 352× · PMID 35773269 · DOI 10.1038/s41392-022-01070-3
  5. Lipogenesis inhibitors: therapeutic opportunities and challenges.
    Batchuluun B, Pinkosky SL, Steinberg GR. · · 2022 · cited 260× · PMID 35031766 · DOI 10.1038/s41573-021-00367-2
  6. Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH).
    Xu X, Poulsen KL, Wu L, Liu S, et al · · 2022 · cited 235× · PMID 35963848 · DOI 10.1038/s41392-022-01119-3
  7. ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials.
    Calle RA, Amin NB, Carvajal-Gonzalez S, Ross TT, et al · · 2021 · cited 166× · PMID 34635855 · DOI 10.1038/s41591-021-01489-1
  8. Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.
    Wu X, Xu M, Geng M, Chen S, et al · · 2023 · cited 161× · PMID 37244925 · DOI 10.1038/s41392-023-01439-y

Verify or expand the search:

Other trials of PF-05221304

Trials testing the same drug.

Other recruiting trials for Nonalcoholic Fatty Liver Disease

Currently open trials in the same condition.

Other Pfizer trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03248882.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing