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.

NCT03776175 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: C3711001
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 29

Brief 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. 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.

Conditions

Non-Alcoholic Fatty Liver Disease (NAFLD)

Outcome Measures

Primary Outcomes (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.

  Baseline, Day 42

Secondary Outcomes (5)

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

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

• Number of Participants With Laboratory Abnormalities

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

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

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

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

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

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

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

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo (PF 05221304) BID Placebo (PF 06865571) BID

Drug: Placebo

PF-05221304 Monotherapy

EXPERIMENTAL

15 mg PF-05221304 BID Placebo (PF-06865571) BID

Drug: PF-05221304 Monotherapy; Drug: Placebo

PF-06865571 Monotherapy

EXPERIMENTAL

Placebo (PF-05221304) BID 300 mg PF-06865571 BID

Drug: PF-06865571 Monotherapy; Drug: Placebo

PF-05221304 and PF-06865571 Combination

EXPERIMENTAL

15 mg PF-05221304 BID 300 mg PF-06865571 BID

Drug: PF-05221304 Monotherapy; Drug: PF-06865571 Monotherapy; Drug: PF-05221304 and PF-06865571 Combination

Interventions

PF-05221304 Monotherapy DRUG

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.

Also known as: Arm B

PF-05221304 Monotherapy; PF-05221304 and PF-06865571 Combination

PF-06865571 Monotherapy DRUG

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.

Also known as: Arm C

PF-05221304 and PF-06865571 Combination; PF-06865571 Monotherapy

Placebo DRUG

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.

Also known as: Arm A

PF-05221304 Monotherapy; PF-06865571 Monotherapy; Placebo

PF-05221304 and PF-06865571 Combination DRUG

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.

Also known as: Arm D

PF-05221304 and PF-06865571 Combination

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (29)

Franco Felizarta, Md

Bakersfield, California, 93301, United States

Location

Westside Medical Associates of Los Angeles

Beverly Hills, California, 90211, United States

Location

ProSciento, Inc.

Chula Vista, California, 91911, United States

Location

National Research Institute - Wilshire

Los Angeles, California, 90057, United States

Location

Catalina Research Institute, LLC

Montclair, California, 91763, United States

Location

Floridian Clinical Research, LLC

Hialeah, Florida, 33016, United States

Location

Research Centers of America, LLC

Hollywood, Florida, 33024, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Pharmax Research Clinic

Miami, Florida, 33126, United States

Location

Omega Research Maitland

Orlando, Florida, 32810, United States

Location

Accel Research Sites

Orlando, Florida, 32819, United States

Location

Advanced Gastroenterology Associates, LLC

Palm Harbor, Florida, 34684, United States

Location

QPS-MRA, LLC-Main Office

South Miami, Florida, 33143, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814, United States

Location

Midwest Institute for Clinical Research

Indianapolis, Indiana, 46260, United States

Location

Heartland Research Associates, LLC

Wichita, Kansas, 67207, United States

Location

L-MARC Research Center

Louisville, Kentucky, 40213, United States

Location

Clarity Clinical Research

East Syracuse, New York, 13057, United States

Location

High Point Clinical Trials Center

High Point, North Carolina, 27265, United States

Location

M3 Wake Research, Inc

Raleigh, North Carolina, 27612, United States

Location

Wake Gastroenterology

Raleigh, North Carolina, 27612, United States

Location

PMG Research of Wilmington, LLC

Wilmington, North Carolina, 28401, United States

Location

Sterling Research Group - Mt. Auburn

Cincinnati, Ohio, 45219, United States

Location

New Horizons Clinical Research

Cincinnati, Ohio, 45242, United States

Location

WR-Clinsearch, LLC

Chattanooga, Tennessee, 37421, United States

Location

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

University of Tennessee Medical Center - Radiology

Knoxville, Tennessee, 37920, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

National Clinical Research-Richmond, Inc.

Richmond, Virginia, 23294, United States

Location

Related Publications (1)

• 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.

  PMID: 34635855 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2018
• First Posted: December 14, 2018
• Study Start: January 4, 2019
• Primary Completion: September 9, 2019
• Study Completion: October 11, 2019
• Last Updated: September 23, 2020
• Results First Posted: September 23, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

US (29)