Study of Pharmacodynamics and Safety of DGAT2i and ACCi Coadministered in Participants With Sponsor-defined Presumed Non Alcoholic Steatohepatitis

March 20, 2023 updated by: Pfizer

A PHASE 2A, 2-PART, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY PLACEBO-CONTROLLED, PARALLEL-GROUP (SPONSOR OPEN) STUDY TO ASSESS PHARMACODYNAMICS AND SAFETY OF PF-06865571 (DGAT2I) COADMINISTERED WITH PF-05221304 (ACCI) IN ADULT PARTICIPANTS WITH PRESUMED NONALCOHOLIC STEATOHEPATITIS (NASH)

The study will evaluate the effect of coadministration of a range of doses of DGAT2i with 1 dose of ACCi, on hepatic steatosis and the ability of DGAT2i to mitigate ACCi-induced elevations in serum triglycerides. The study has a 2-part design with sequential conduct of Part 1 and Part 2 with each part conducted in distinct/separate cohorts of participants. The overall study design, objectives/endpoints, eligibility criteria for both parts is envisioned to be identical, however, data from Part 1 will be used to determine whether to conduct Part 2.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Quebec, Canada, G2J 0C4
        • Alpha Recherche Clinique
      • Quebec, Canada, G1W 4R4
        • Centre de Recherche Saint-Louis
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 1V7
        • Nova Scotia Health Authority QE II Health Sciences Centre
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Nova Scotia Health Authority QE II Health Sciences Centre
      • Halifax, Nova Scotia, Canada, B3K 4N1
        • Nova Scotia Health Authority - Queen Elizabeth II Health Sciences Centre
    • Ontario
      • Brampton, Ontario, Canada, L6T 0G1
        • Aggarwal and Associates Limited
      • London, Ontario, Canada, N5W 6A2
        • Milestone Research Inc.
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 7K9
        • Ecogene-21
      • Chicoutimi, Quebec, Canada, G7H 4J1
        • Resonance Magnetique du Saguenay-Lac-Saint-Jean
  • United States
    • California
      • Lincoln, California, United States, 95648
        • Clinical Trials Research
      • Montclair, California, United States, 91763
        • Catalina Research Institute, LLC
    • Florida
      • Boca Raton, Florida, United States, 33434
        • Excel Medical Clinical Trials
      • Miami, Florida, United States, 33125
        • Optimus U Corporation
      • Miami Lakes, Florida, United States, 33016
        • Floridian Clinical Research, LLC
    • Hawaii
      • Honolulu, Hawaii, United States, 96814
        • East-West Medical Research Institute
    • Kentucky
      • Louisville, Kentucky, United States, 40213
        • L-MARC Research Center
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • The Christ Hospital
      • Cincinnati, Ohio, United States, 45246
        • Sterling Research Group, Ltd.
    • Texas
      • San Antonio, Texas, United States, 78229
        • Clinical Trials of Texas, Inc.
    • Virginia
      • Richmond, Virginia, United States, 23294
        • National Clinical Research, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • BMI ≥25 and ≤ 40 kg/m2
  • concomitant medical conditions associated with NAFLD

Exclusion Criteria:

  • Evidence of other causes of liver disease such as Alcoholic steatohepatitis, (de)compensated cirrhosis, active viral hepatitis
  • Any condition possibly affecting drug absorption
  • Unstable liver function tests
  • Recent cardiovascular event(s),
  • Malignancies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Participants will receive medication for 6 weeks
Drug: Placebo
Tablet
Experimental: DGAT2i (25 mg BID) + ACCi (10 mg BID)
Participants will receive medication for 6 weeks
Drug: PF-06865571
Tablet
Other Names:
  • DGAT2i
Drug: PF-05221304
Tablet
Other Names:
  • ACCi
Experimental: DGAT2i (100 mg BID) + ACCi (10 mg BID)
Participants will receive medication for 6 weeks
Drug: PF-06865571
Tablet
Other Names:
  • DGAT2i
Drug: PF-05221304
Tablet
Other Names:
  • ACCi
Experimental: DGAT2i (300 mg QD) + ACCi (20 mg QD)
Participants will receive medication for 6 weeks
Drug: PF-06865571
Tablet
Other Names:
  • DGAT2i
Drug: PF-05221304
Tablet
Other Names:
  • ACCi
Experimental: DGAT2i (300 mg BID) + ACCi (10 mg BID)
Participants will receive medication for 6 weeks
Drug: PF-06865571
Tablet
Other Names:
  • DGAT2i
Drug: PF-05221304
Tablet
Other Names:
  • ACCi

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline (CFB) in Percent (%) Liver Fat as Assessed Via Magnetic Resonance Imaging Using Proton Density Fat Fraction Acquisition (MRI-PDFF) at Week 6
Time Frame: Baseline, Week 6
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 = the sum of PDFFs for (Segment I + Segment II + Segment III + Segment IVa + Segment IVb + Segment V + Segment VI + Segment VII + Segment VIII) divided by (number of segments assessed and no missing/mapping at Baseline, and on Week 6). If some segments did not have results reported at Baseline and/or Week 6, liver PDFF was to be calculated using data in segments that had data available at both Baseline visit and Week 6 visit. For this outcome measure (OM), baseline is defined as the assessment undertaken between Visit 3/Week -2 and Visit 4/Day 1.
Baseline, Week 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent CFB in Fasting Serum Triglycerides at Week 6
Time Frame: Baseline, Week 6
Blood samples were collected before morning dose for the measurement of fasting serum triglycerides. Natural log transformed relative changes from baseline in fasting serum triglycerides were analyzed using mixed model repeated measures (MMRM) analysis with treatment, week and treatment by-week interaction as fixed effects, participant as random effect and log transformed baseline as a covariate using unstructured covariance structure. Values were back-transformed from the log scale. Relative change was converted to percent change as follows: Percent change = 100*(RC-1). For this OM, baseline is defined as the result closest prior to dosing on Day 1 (either predose on Day 1/Visit 4 or Week -2/Visit 3).
Baseline, Week 6
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Baseline up to at least 28 days after the last administration of the study intervention or until study completion or withdrawal, whichever was longer (maximum of approximately 24 weeks).
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=all AEs included in the AE Case Report Form (CRF) page during the study. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; or resulted in congenital anomaly/birth defect. Severe TEAEs were defined as AEs that prevent normal everyday activities. Treatment-related TEAEs were determined by the investigator.
Baseline up to at least 28 days after the last administration of the study intervention or until study completion or withdrawal, whichever was longer (maximum of approximately 24 weeks).
Number of Participants With TEAEs of Special Interest by Preferred Term (PT)
Time Frame: Baseline up to at least 28 days after the last administration of the study intervention or until study completion or withdrawal, whichever was longer (maximum of approximately 24 weeks).
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=all AEs included in the AE CRF page during the study. A 3-tier approach was used to summarize and classify TEAEs into 1 of 3 tiers by the investigator based on their incidence rate and clinical importance to the trial. Tier-1 events = pre-specified events of clinical importance that are maintained in a program level list. Tier-2 events = events that are not tier-1 but are "common". A Medical Dictionary for Regulatory Activities Terminology (MedDRA) PT is defined as a tier-2 event if there are at least 4 participants with at least one occurrence in any treatment group, to distinguish Tier-2 events from Tier-3 events. Tier-3 events = events that do not meet criteria for either tier-1 or tier-2 event. TEAE(s) of special interest reported in at least 1 participant are presented in this OM.
Baseline up to at least 28 days after the last administration of the study intervention or until study completion or withdrawal, whichever was longer (maximum of approximately 24 weeks).
Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
Time Frame: From baseline to end of follow-up or until study discontinuation/withdrawal, whichever was longer (maximum of approximately 19 weeks)
Participants with laboratory test abnormalities (hematology, chemistry and urinalysis) meeting pre-specified criteria are reported without regard to baseline abnormality. LLN is lower limit of normal. ULN is upper limit of normal. Baseline was defined as the result closest prior to Day 1 dosing.
From baseline to end of follow-up or until study discontinuation/withdrawal, whichever was longer (maximum of approximately 19 weeks)
Number of Participants With Abnormalities in Laboratory Parameters of Special Interest Meeting Pre-Defined Criteria
Time Frame: From baseline to end of follow-up or until study discontinuation/withdrawal, whichever was longer (maximum of approximately 19 weeks)
Laboratory parameters of special interest included fasting serum triglycerides, platelet count, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, and fasting plasma glucose. Pre-specified criteria for laboratory parameters of special interest included flag level threshold (reflecting either the threshold for study entry or clinical significance) and alert level threshold (requiring rapid notification to site and study team when values exceeding the threshold were noted during the study). All flag level changes and alert level changes were cumulative from baseline (defined as result closest prior to dosing at Day 1). LLN is lower limit of normal. ULN is upper limit of normal.
From baseline to end of follow-up or until study discontinuation/withdrawal, whichever was longer (maximum of approximately 19 weeks)
Number of Participants With Post-Baseline Vital Signs Data Meeting Pre-Defined Criteria
Time Frame: Baseline, Week 6, the first follow-up visit (Week 8), and the date of discontinuation/withdrawal from study (maximum of approximately 12 weeks after Day 1) if applicable
Pre-defined categorical criteria for vital signs data of special clinical concern included: seated systolic blood pressure (BP) absolute value <90 mmHg or change from baseline >=30 mmHg, seated diastolic BP absolute value <50 mmHg or change from baseline >=20 mmHg, seated pulse rate absolute value <40 beats per minute (bpm) or >120 bpm. Baseline was defined as the result closest prior to Day 1 dosing.
Baseline, Week 6, the first follow-up visit (Week 8), and the date of discontinuation/withdrawal from study (maximum of approximately 12 weeks after Day 1) if applicable
Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Pre-Defined Criteria
Time Frame: Baseline, Week 6, the first follow-up visit (Week 8), and the date of discontinuation/withdrawal from study (maximum of approximately 12 weeks after Day 1) if applicable
Pre-defined categorical criteria for ECG data of special clinical concern included: (1) QTc interval absolute value >450 and <=480 msec (mild prolongation), >480 and <=500 msec (moderate prolongation), >500 msec (severe prolongation); (2) QTc interval increase from baseline >=30 and <=60 msec (moderate prolongation), or >60 msec (severe prolongation); (3) uncorrected QT interval >500 msec. ECG abnormalities meeting prespecified criteria and reported in at least 1 participant are presented in this OM. Baseline was defined as the result closest prior to Day 1 dosing.
Baseline, Week 6, the first follow-up visit (Week 8), and the date of discontinuation/withdrawal from study (maximum of approximately 12 weeks after Day 1) if applicable

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 10, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 28, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 20, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 22, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 13, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • C3711005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings