Clinical trial NCT03776175: 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.
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Alcoholic Fatty Liver Disease (NAFLD)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-12-14
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42
timeFrame: Baseline, Day 42
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 35 days from last dose of study drug or early termination: (maximum up to Day 77)
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to 35 days last from dose of study drug or early termination (maximum up to Day 77)
measure: Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure
timeFrame: Baseline, Post-last dose of study drug (up to Day 42)
measure: Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate
timeFrame: Baseline, Post- last dose of study drug (up to Day 42)
measure: Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria
timeFrame: Baseline up to 35 days last dose of study drug or early termination (maximum up to Day 77)
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Franco Felizarta, Md
state: California
city: Beverly Hills
country: United States
facility: Westside Medical Associates of Los Angeles
state: California
city: Chula Vista
country: United States
facility: ProSciento, Inc.
state: California
city: Los Angeles
country: United States
facility: National Research Institute - Wilshire
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Hialeah
country: United States
facility: Floridian Clinical Research, LLC
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America, LLC
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic
state: Florida
city: Orlando
country: United States
facility: Omega Research Maitland
state: Florida
city: Orlando
country: United States
facility: Accel Research Sites
state: Florida
city: Palm Harbor
country: United States
facility: Advanced Gastroenterology Associates, LLC
state: Florida
city: South Miami
country: United States
facility: QPS-MRA, LLC-Main Office
state: Florida
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research
state: Indiana
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: East Syracuse
country: United States
facility: Clarity Clinical Research
state: New York
city: High Point
country: United States
facility: High Point Clinical Trials Center
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research, Inc
state: North Carolina
city: Raleigh
country: United States
facility: Wake Gastroenterology
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Sterling Research Group - Mt. Auburn
state: Ohio
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Chattanooga
country: United States
facility: WR-Clinsearch, LLC
state: Tennessee
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center - Radiology
state: Tennessee
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Richmond
country: United States
facility: National Clinical Research-Richmond, Inc.
state: Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.