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Non-Alcoholic Fatty Liver Disease (NAFLD)Phase 2NCT03776175

A Study To Assess Pharmacodynamics, Safety And Tolerability Of PF-05221304 And PF-06865571 Co-Administered For 6 Weeks In Adults With Non-Alcoholic Fatty Liver Disease.

A Phase 2 study testing PF-05221304 Monotherapy, PF-06865571 Monotherapy and PF-05221304 and PF-06865571 Combination in people with Non-Alcoholic Fatty Liver Disease (NAFLD), run by Pfizer at 29 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
PF-05221304 Monotherapy, PF-06865571 Monotherapy and PF-05221304 and PF-06865571 Combination
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
99 participants
Where
29 sitesUnited States
Study dates
4 Jan 2019to 11 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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

Who cannot join

  • 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;
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  • 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 1.3.
  • 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/1.73m2.
  • 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

Trial locations and contacts

29 sites in 1 country.

29 sites in 1 country

United States29 sites

  • Franco Felizarta, Md

    Bakersfield, California, 93301

  • Westside Medical Associates of Los Angeles

    Beverly Hills, California, 90211

  • WR-Clinsearch, LLC

    Chattanooga, Tennessee, 37421

  • ProSciento, Inc.

    Chula Vista, California, 91911

  • Sterling Research Group - Mt. Auburn

    Cincinnati, Ohio, 45219

  • New Horizons Clinical Research

    Cincinnati, Ohio, 45242

  • Clarity Clinical Research

    East Syracuse, New York, 13057

  • Floridian Clinical Research, LLC

    Hialeah, Florida, 33016

  • High Point Clinical Trials Center

    High Point, North Carolina, 27265

  • Research Centers of America, LLC

    Hollywood, Florida, 33024

  • East-West Medical Research Institute

    Honolulu, Hawaii, 96814

  • Midwest Institute for Clinical Research

    Indianapolis, Indiana, 46260

  • Jacksonville Center for Clinical Research

    Jacksonville, Florida, 32216

  • New Orleans Center for Clinical Research

    Knoxville, Tennessee, 37920

  • University of Tennessee Medical Center - Radiology

    Knoxville, Tennessee, 37920

  • National Research Institute - Wilshire

    Los Angeles, California, 90057

  • L-MARC Research Center

    Louisville, Kentucky, 40213

  • Pharmax Research Clinic

    Miami, Florida, 33126

  • Catalina Research Institute, LLC

    Montclair, California, 91763

  • Omega Research Maitland

    Orlando, Florida, 32810

  • Accel Research Sites

    Orlando, Florida, 32819

  • Advanced Gastroenterology Associates, LLC

    Palm Harbor, Florida, 34684

  • M3 Wake Research, Inc

    Raleigh, North Carolina, 27612

  • Wake Gastroenterology

    Raleigh, North Carolina, 27612

  • National Clinical Research-Richmond, Inc.

    Richmond, Virginia, 23294

  • Clinical Trials of Texas, Inc.

    San Antonio, Texas, 78229

  • QPS-MRA, LLC-Main Office

    South Miami, Florida, 33143

  • Heartland Research Associates, LLC

    Wichita, Kansas, 67207

  • PMG Research of Wilmington, LLC

    Wilmington, North Carolina, 28401

Other trials in United States

About this study

Official title: 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)

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.

Being tested
PF-05221304 Monotherapy, PF-06865571 Monotherapy, Placebo, PF-05221304 and PF-06865571 Combination
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-05221304 MonotherapyDrug

    Also called Arm B

    Participants enrolled in this Arm will receive 15 mg dose of PF-05221304 (3 tablets of 5 mg each) and 3 tablets of Placebo for PF-06865571, each to be taken twice daily for 41 days and once on Day 42.

  • PF-06865571 MonotherapyDrug

    Also called Arm C

    Participants enrolled in this Arm will receive 300 mg dose of PF-06865571 (3 tablets of 100 mg each) and 3 tablets of Placebo for PF-05221304, all to be taken twice daily for 41 days and once on Day 42.

  • PlaceboDrug

    Also called Arm A

    Participants enrolled in this Arm will receive 3 tablets for Placebo of PF-05221304 and 3 tablets of Placebo of PF-06865571, to be taken twice daily for 41 days and once on Day 42.

  • PF-05221304 and PF-06865571 CombinationDrug

    Also called Arm D

    Participants enrolled in this Arm will receive 15 mg dose of PF-05221304 (3 tablets of 5 mg each) and 3 tablets of PF-06865571 (3 tablets of 100 mg each), each to be taken twice daily for 41 days and once on Day 42.

Study groups in NCT03776175
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo (PF 05221304) BID Placebo (PF 06865571) BID
Receives: Drug: Placebo
PF-05221304 MonotherapyExperimental15 mg PF-05221304 BID Placebo (PF-06865571) BID
Receives: Drug: PF-05221304 Monotherapy; Drug: Placebo
PF-06865571 MonotherapyExperimentalPlacebo (PF-05221304) BID 300 mg PF-06865571 BID
Receives: Drug: PF-06865571 Monotherapy; Drug: Placebo
PF-05221304 and PF-06865571 CombinationExperimental15 mg PF-05221304 BID 300 mg PF-06865571 BID
Receives: Drug: PF-05221304 Monotherapy; Drug: PF-06865571 Monotherapy; Drug: PF-05221304 and PF-06865571 Combination

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at 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.

    Measured: Baseline, Day 42

Secondary outcomes (5)

  1. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included all serious and non-serious adverse events.

    Measured: Baseline up to 35 days from last dose of study drug or early termination: (maximum up to Day 77)

  2. Number of Participants With Laboratory Abnormalities

    Clinical chemistry: Bilirubin (milligram per deciliter [mg/dL]), direct bilirubin (mg/dL)>3.0*upper limit of normal (ULN), alanine aminotransferase international units per liter (U/L), aspartate aminotransferase (U/L), alkaline phosphatase (U/L), gamma glutamyl transferase (U/L)>5.0*ULN, urea nitrogen (mg/dL)>2.0*ULN, low density lipoprotein direct endpoint measure (mg/dL)>1.5*ULN, triglycerides (mg/dL)>2.0*ULN, creatinine based estimated glomerular filtration rate by modification of diet in renal disease equation and cystatin based eGFR by chronic kidney disease epidemiology collaboration equation (C <60 milliliter per minute per 1.73 square of meter), very low density lipoprotein (millimoles per liter), Cholesterol >2.0*ULN.

    Measured: Baseline up to 35 days last from dose of study drug or early termination (maximum up to Day 77)

  3. Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure

    Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate.

    Measured: Baseline, Post-last dose of study drug (up to Day 42)

  4. Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate

    Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate.

    Measured: Baseline, Post- last dose of study drug (up to Day 42)

  5. Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria

    ECG criteria included: 1) PR interval (milliseconds [msec]): baseline greater than (>) 200 msec and maximum increase from baseline greater than or equal to (>=) 25 percent (%) or baseline less than or equal to (<=) 200 msec and maximum increase from baseline >=50%; 2) QRS interval (msec): maximum increase from baseline >=50%; 3) QT interval corrected using Fridericia's formula (QTcF): a) change from baseline >30 msec and <=60 msec, b) change from baseline >60 msec.

    Measured: Baseline up to 35 days last dose of study drug or early termination (maximum up to Day 77)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2018
  2. Study start4 Jan 2019
  3. Primary completion9 Sep 2019
  4. Study completion11 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
99 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03776175
Sponsor's protocol ID
C3711001
Status last verified
Sep 2020
First submitted
12 Dec 2018
Last updated
23 Sep 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Calle RA, Amin NB, Carvajal-Gonzalez S, Ross TT, Bergman A, Aggarwal S, Crowley C, Rinaldi A, Mancuso J, Aggarwal N, Somayaji V, Inglot M, Tuthill TA, Kou K, Boucher M, Tesz G, Dullea R, Bence KK, Kim AM, Pfefferkorn JA, Esler WP. 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. Nat Med. 2021 Oct;27(10):1836-1848. doi: 10.1038/s41591-021-01489-1. Epub 2021 Oct 11.

    PubMed 34635855

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PF-05221304 Monotherapy, PF-06865571 Monotherapy and PF-05221304 and PF-06865571 Combination in people with Non-Alcoholic Fatty Liver Disease (NAFLD), run by Pfizer at 29 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42 (time frame: Baseline, Day 42). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03776175, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2020.

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