2-Week Study In People With Nonalcoholic Fatty Liver Disease

• ClinicalTrials.gov Identifier: NCT03513588
• Recruitment Status: Completed
• First Posted: May 1, 2018
• Results First Posted: March 13, 2020
• Last Update Posted: March 13, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

2-week study in people with nonalcoholic fatty liver disease. Study drug at 1 of 2 doses, or placebo, will be given for 14 days. Blood samples, heart monitoring, vital signs, and imaging procedures will be performed.

Condition or disease	Intervention/treatment	Phase
Non-alcoholic Steatohepatitis; Non-alcoholic Fatty Liver Disease	Drug: Placebo; Drug: PF-06865571	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A PHASE 1B, RANDOMIZED, DOUBLE-BLIND (SPONSOR-OPEN), PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACODYNAMICS AND PHARMACOKINETICS OF MULTIPLE ORAL DOSES OF PF- 06865571 FOR 2 WEEKS IN ADULTS WITH NONALCOHOLIC FATTY LIVER DISEASE
• Actual Study Start Date: June 21, 2018
• Actual Primary Completion Date: March 8, 2019
• Actual Study Completion Date: April 4, 2019

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo	Drug: Placebo; tablet, 0 mg, 14 days, every 12 hours
Experimental: PF-06865571 100 mg	Drug: PF-06865571; tablet, 50 mg, 14 days, every 12 hours
Experimental: PF-06865571 600 mg	Drug: PF-06865571; tablet, 300 mg, 14 days, every 12 hours

Outcome Measures

Primary Outcome Measures :

1. Relative Change From Baseline in Whole Liver Fat at Day 15 as Assessed by Magnetic Resonance Imaging (MRI) - Proton Density Fat Fraction (PDFF) [ Time Frame: Baseline (Day 1), Day 15 ]
   MRI-PDFF is an established method that enables quantification of fat content in the liver. The value of whole liver fat as assessed by MRI-PDFF is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level.

Secondary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study treatment up to 28-35 days after last dose (maximum of up to 49 days) ]
   An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs.
2. Number of Participants With Laboratory Test Abnormalities [ Time Frame: From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days) ]
   Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes); chemistry (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, sodium, potassium, calcium, chloride, bicarbonate); urinalysis (urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, urine erythrocytes, urine leukocytes, hyaline casts); biomarker (total cholesterol, low-density and high-density lipoprotein cholesterol, triglycerides, fasting glucose). Participants with any of the laboratory test abnormalities were counted.
3. Number of Participants With Vital Sign Abnormalities [ Time Frame: From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days) ]
   Vital sign categorical summarization criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine DBP greater than or equal to (>=) 20 mmHg; 5) change from baseline (increase or decrease) in supine SBP >=30 mmHg.
4. Number of Participants With Electrocardiogram (ECG) Abnormalities [ Time Frame: From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days) ]
   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), >=50% change from baseline; 2) 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, >=25% change when baseline is > 200 msec or >=50% change when baseline is less than or equal to (<=) 200 msec; 3) QTcF interval (heart rate corrected QT [time between the start of the ECG Q wave and the end of the T wave in the heart's electrical cycle] using Fridericia's formula): absolute value of >450 to 480 msec, >480 to 500 msec, >500 msec; a change from baseline of >30 to 60 msec or >60 msec.
5. Maximum Plasma Concentration (Cmax) For PF-06865571 [ Time Frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose ]
   Cmax of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages.
6. Area Under the Plasma Concentration-Time Profile Over the Dosing Interval (AUCtau) For PF-06865571 [ Time Frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose ]
   AUCtau of PF-06865571 on Day 14 was obtained by linear/log trapezoidal method. The dosing interval (tau) was 12 hours. Geometric coefficients of variations were reported as percentages.
7. Time to Reach Maximum Plasma Concentration (Tmax) For PF-06865571 [ Time Frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose ]
   Tmax of PF-06865571 on Day 14 was observed directly from data as time of Cmax occurrence.
8. Minimum Plasma Concentration (Cmin) For PF-06865571 [ Time Frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose ]
   Cmin of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages.
9. Apparent Oral Clearance (CL/F) For PF-06865571 [ Time Frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose ]
   CL/F of PF-06865571 on Day 14 was calculated as Dose/AUCtau. Geometric coefficients of variations were reported as percentages.
10. Peak-to-Trough Ratio (PTR) For PF-06865571 [ Time Frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose ]
    PTR of PF-06865571 on Day 14 was calculated as Cmax/Cmin. Geometric coefficients of variations were reported as percentages.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• controlled attenuation parameter greater than or equal to 260 dB/m via FibroScan
• liver fat greater than or equal to 6% via MRI

Exclusion Criteria:

• Chronic liver disease
• Type 2 diabetes requiring drug treatment
• Unable to undergo MRI
• History of heart attack or stroke

Contacts and Locations

Locations

United States, California

Anaheim Clinical Trials, LLC

Anaheim, California, United States, 92801

United States, Connecticut

New Haven Clinical Research Unit

New Haven, Connecticut, United States, 06511

United States, Florida

Qps-Mra, Llc

South Miami, Florida, United States, 33143

United States, Nevada

PPD Development, LP

Las Vegas, Nevada, United States, 89113

United States, North Carolina

High Point Clinical Trials Center

High Point, North Carolina, United States, 27265

United States, Texas

Clinical Trials of Texas, Inc.

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] February 27, 2018

Statistical Analysis Plan  [PDF] May 17, 2018

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03513588
• Other Study ID Numbers: C2541005
• First Posted: May 1, 2018
• Results First Posted: March 13, 2020
• Last Update Posted: March 13, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases