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.

NCT ID: NCT03776175

Last Updated: 2020-09-23

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

99 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-04

Study Completion Date

2019-10-11

Brief Summary

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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.

Detailed Description

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Conditions

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Non-Alcoholic Fatty Liver Disease (NAFLD)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

PF-05221304 Monotherapy

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

Group Type EXPERIMENTAL

PF-05221304 Monotherapy

Intervention Type 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.

Placebo

Intervention Type 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.

PF-06865571 Monotherapy

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

Group Type EXPERIMENTAL

PF-06865571 Monotherapy

Intervention Type 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.

Placebo

Intervention Type 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.

PF-05221304 and PF-06865571 Combination

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

Group Type EXPERIMENTAL

PF-05221304 Monotherapy

Intervention Type 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.

PF-06865571 Monotherapy

Intervention Type 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.

PF-05221304 and PF-06865571 Combination

Intervention Type 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.

Interventions

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PF-05221304 Monotherapy

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.

Intervention Type DRUG

PF-06865571 Monotherapy

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

PF-05221304 and PF-06865571 Combination

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.

Intervention Type DRUG

Other Intervention Names

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Arm B Arm C Arm A Arm D

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Franco Felizarta, Md

Bakersfield, California, United States

Site Status

Westside Medical Associates of Los Angeles

Beverly Hills, California, United States

Site Status

ProSciento, Inc.

Chula Vista, California, United States

Site Status

National Research Institute - Wilshire

Los Angeles, California, United States

Site Status

Catalina Research Institute, LLC

Montclair, California, United States

Site Status

Floridian Clinical Research, LLC

Hialeah, Florida, United States

Site Status

Research Centers of America, LLC

Hollywood, Florida, United States

Site Status

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Pharmax Research Clinic

Miami, Florida, United States

Site Status

Omega Research Maitland

Orlando, Florida, United States

Site Status

Accel Research Sites

Orlando, Florida, United States

Site Status

Advanced Gastroenterology Associates, LLC

Palm Harbor, Florida, United States

Site Status

QPS-MRA, LLC-Main Office

South Miami, Florida, United States

Site Status

East-West Medical Research Institute

Honolulu, Hawaii, United States

Site Status

Midwest Institute for Clinical Research

Indianapolis, Indiana, United States

Site Status

Heartland Research Associates, LLC

Wichita, Kansas, United States

Site Status

L-MARC Research Center

Louisville, Kentucky, United States

Site Status

Clarity Clinical Research

East Syracuse, New York, United States

Site Status

High Point Clinical Trials Center

High Point, North Carolina, United States

Site Status

M3 Wake Research, Inc

Raleigh, North Carolina, United States

Site Status

Wake Gastroenterology

Raleigh, North Carolina, United States

Site Status

PMG Research of Wilmington, LLC

Wilmington, North Carolina, United States

Site Status

Sterling Research Group - Mt. Auburn

Cincinnati, Ohio, United States

Site Status

New Horizons Clinical Research

Cincinnati, Ohio, United States

Site Status

WR-Clinsearch, LLC

Chattanooga, Tennessee, United States

Site Status

New Orleans Center for Clinical Research

Knoxville, Tennessee, United States

Site Status

University of Tennessee Medical Center - Radiology

Knoxville, Tennessee, United States

Site Status

Clinical Trials of Texas, Inc.

San Antonio, Texas, United States

Site Status

National Clinical Research-Richmond, Inc.

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 34635855 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=C3711001

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

Other Identifiers

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C3711001

Identifier Type: -

Identifier Source: org_study_id

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