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A Phase I Pharmacokinetic Study of TVB-2640 (Denifanstat) in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Subjects With Normal Hepatic Function

Primary Purpose

Non-alcoholic Steatohepatitis, Hepatic Impairment, Cirrhosis

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TVB-2640 - 50 mg
Sponsored by
Sagimet Biosciences Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-alcoholic Steatohepatitis focused on measuring NASH, Hepatic impairment, Cirrhosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Key Inclusion Criteria: Subjects must satisfy all of the following criteria at the Screening visit unless otherwise stated: All Subjects Males or females, of any race, between 18 and 75 years of age, inclusive. Body mass index between 18.0 and 42.0/45.0 kg/m2 (inclusive; up to 42.0 kg/m2 for subjects without ascites and 45.0 kg/m2 for subjects with ascites) Females will not be pregnant or lactating, and females of childbearing potential (premenopausal females who are anatomically and physiologically capable of becoming pregnant following menarche) and males will agree to use contraception as detailed in the protocol. Subjects with Hepatic Impairment Only Documented chronic stable liver disease; diagnosis of cirrhosis due to parenchymal liver disease. T Subjects with mild, moderate, or severe hepatic impairment may have medical findings consistent with their hepatic dysfunction. Non-hepatic, abnormal clinical laboratory evaluations must not be clinically relevant. Currently on a stable medication regimen; Concomitant medications administered within 30 days prior to the first dose administration (Day 1) must be approved by the Investigator (or designee), Sponsor, and the Medical Monitor. Anemia secondary to hepatic disease will be acceptable if hemoglobin > 9 g/dL and anemia symptoms are not clinically significant as judged by the Investigator (or designee) and the Medical Monitor. Subjects must have a platelet count ≥ 35 × 109 platelets/L for mild and moderate hepatic impairment subjects and ≥ 30 × 109 platelets/L for severe hepatic impairment subjects. Subjects with diabetes mellitus may be included, provided the subjects have: Hemoglobin A1c values ≤ 9.0% at Screening. Subjects with values outside this range may be allowed by the Medical Monitor on a case-by-case basis. Medications for the treatment of diabetes mellitus must be reviewed and approved by the Investigator (or designee), Medical Monitor, and Sponsor. Key Exclusion Criteria: Subjects will be excluded from the study if they satisfy any of the following criteria at the Screening visit unless otherwise stated: All Subjects Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee). History of corneal edema, keratitis, xerophthalmia (dry eye), or other corneal abnormalities. Subjects may wear contact lenses during the study with the exception of the day of dosing (Days 1 to Day 4). History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (except uncomplicated appendectomy, hernia repair, and cholecystectomy will be allowed; bariatric surgery will not be allowed). Ventricular dysfunction or history of risk factors for Torsade de Pointes. Subjects will be excluded if there is a family history of long QT syndrome. Evidence of hepatorenal syndrome and Cockcroft-Gault estimated creatinine clearance (CrCl) ≤ 60 mL/min/1.73 m2 for mild and moderate hepatic impairment subjects, ≤ 50 mL/min/1.73 m2 for severe hepatic impairment subjects or clinically significant abnormal sodium and potassium levels, as determined by the Investigator (or designee), at Screening or Check-in (Day 1). Use or intended use of any medications/products known to alter drug absorption, metabolism, or elimination processes. Use of any strong inhibitors or inducers of cytochrome P450 (CYP)2C9 or CYP3A4/5, or inhibitors of CYP3A4 within 30 days prior to first dose administration (Day 1). Alcohol consumption of > 21 units per week for males and > 14 units for females. Positive urine drug screen Positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) test at Screening and Check-in (Day -1), history of hospitalization for coronavirus disease-2019 (COVID-19), or history of use of oxygen due to COVID-19. Note that previous COVID-19 infection alone is not exclusionary and vaccination against SARS-CoV-2 is allowed but must be documented.

Sites / Locations

  • Thomas C. MarburyRecruiting
  • Eric J. Lawitz, MDRecruiting
  • Geza Lakner

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

TVB-2640 50 mg - normal hepatic function

TVB-2640 50 mg - mild hepatic function

TVB-2640 50 mg - moderate hepatic function

TVB-2640 50 mg - severe hepatic function

Arm Description

Healthy subjects with normal hepatic function receive 50 mg PO daily from Day 1 to Day 4

Subjects with mild hepatic impairment will receive 50 mg PO daily from Day 1 to Day 4

Subjects with moderate hepatic impairment will receive 50 mg PO daily from Day 1 to Day 4

Subjects with severe hepatic impairment will receive 50 mg PO daily from Day 1 to Day 4

Outcomes

Primary Outcome Measures

Total TVB-2640 plasma concentration-time (AUC) at steady state
Total TVB-2640 plasma concentration-time curve during a dosing interval at steady-state
Unbound TVB-2640 plasma concentration-time (AUC) at steady state
Unbound TVB-2640 plasma concentration-time curve during a dosing interval at steady-state
Maximum plasma concentration (Cmax) for total TVB-2640 at steady state
Maximum plasma concentration (Cmax) for unbound TVB-2640 at steady state
incidence and severity of AEs

Secondary Outcome Measures

Full Information

First Posted
April 17, 2023
Last Updated
May 3, 2023
Sponsor
Sagimet Biosciences Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05835180
Brief Title
A Phase I Pharmacokinetic Study of TVB-2640 (Denifanstat) in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Subjects With Normal Hepatic Function
Official Title
A Phase I, Open-label, Pharmacokinetic Study of TVB-2640 in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Subjects With Normal Hepatic Function
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Actual)
Primary Completion Date
October 9, 2023 (Anticipated)
Study Completion Date
October 9, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sagimet Biosciences Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this phase 1 study is to assess the pharmacokinetics, safety and tolerability following multiple oral doses of TVB-2640 in subjects with mild, moderate, or severe hepatic impairment compared to healthy subjects with normal hepatic function.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Steatohepatitis, Hepatic Impairment, Cirrhosis
Keywords
NASH, Hepatic impairment, Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TVB-2640 50 mg - normal hepatic function
Arm Type
Experimental
Arm Description
Healthy subjects with normal hepatic function receive 50 mg PO daily from Day 1 to Day 4
Arm Title
TVB-2640 50 mg - mild hepatic function
Arm Type
Experimental
Arm Description
Subjects with mild hepatic impairment will receive 50 mg PO daily from Day 1 to Day 4
Arm Title
TVB-2640 50 mg - moderate hepatic function
Arm Type
Experimental
Arm Description
Subjects with moderate hepatic impairment will receive 50 mg PO daily from Day 1 to Day 4
Arm Title
TVB-2640 50 mg - severe hepatic function
Arm Type
Experimental
Arm Description
Subjects with severe hepatic impairment will receive 50 mg PO daily from Day 1 to Day 4
Intervention Type
Drug
Intervention Name(s)
TVB-2640 - 50 mg
Intervention Description
TVB-2640 -50 mg administered orally once daily
Primary Outcome Measure Information:
Title
Total TVB-2640 plasma concentration-time (AUC) at steady state
Description
Total TVB-2640 plasma concentration-time curve during a dosing interval at steady-state
Time Frame
Day 4
Title
Unbound TVB-2640 plasma concentration-time (AUC) at steady state
Description
Unbound TVB-2640 plasma concentration-time curve during a dosing interval at steady-state
Time Frame
Day 4
Title
Maximum plasma concentration (Cmax) for total TVB-2640 at steady state
Time Frame
Day 4
Title
Maximum plasma concentration (Cmax) for unbound TVB-2640 at steady state
Time Frame
Day 4
Title
incidence and severity of AEs
Time Frame
Screening to Day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Key Inclusion Criteria: Subjects must satisfy all of the following criteria at the Screening visit unless otherwise stated: All Subjects Males or females, of any race, between 18 and 75 years of age, inclusive. Body mass index between 18.0 and 42.0/45.0 kg/m2 (inclusive; up to 42.0 kg/m2 for subjects without ascites and 45.0 kg/m2 for subjects with ascites) Females will not be pregnant or lactating, and females of childbearing potential (premenopausal females who are anatomically and physiologically capable of becoming pregnant following menarche) and males will agree to use contraception as detailed in the protocol. Subjects with Hepatic Impairment Only Documented chronic stable liver disease; diagnosis of cirrhosis due to parenchymal liver disease. T Subjects with mild, moderate, or severe hepatic impairment may have medical findings consistent with their hepatic dysfunction. Non-hepatic, abnormal clinical laboratory evaluations must not be clinically relevant. Currently on a stable medication regimen; Concomitant medications administered within 30 days prior to the first dose administration (Day 1) must be approved by the Investigator (or designee), Sponsor, and the Medical Monitor. Anemia secondary to hepatic disease will be acceptable if hemoglobin > 9 g/dL and anemia symptoms are not clinically significant as judged by the Investigator (or designee) and the Medical Monitor. Subjects must have a platelet count ≥ 35 × 109 platelets/L for mild and moderate hepatic impairment subjects and ≥ 30 × 109 platelets/L for severe hepatic impairment subjects. Subjects with diabetes mellitus may be included, provided the subjects have: Hemoglobin A1c values ≤ 9.0% at Screening. Subjects with values outside this range may be allowed by the Medical Monitor on a case-by-case basis. Medications for the treatment of diabetes mellitus must be reviewed and approved by the Investigator (or designee), Medical Monitor, and Sponsor. Key Exclusion Criteria: Subjects will be excluded from the study if they satisfy any of the following criteria at the Screening visit unless otherwise stated: All Subjects Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee). History of corneal edema, keratitis, xerophthalmia (dry eye), or other corneal abnormalities. Subjects may wear contact lenses during the study with the exception of the day of dosing (Days 1 to Day 4). History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (except uncomplicated appendectomy, hernia repair, and cholecystectomy will be allowed; bariatric surgery will not be allowed). Ventricular dysfunction or history of risk factors for Torsade de Pointes. Subjects will be excluded if there is a family history of long QT syndrome. Evidence of hepatorenal syndrome and Cockcroft-Gault estimated creatinine clearance (CrCl) ≤ 60 mL/min/1.73 m2 for mild and moderate hepatic impairment subjects, ≤ 50 mL/min/1.73 m2 for severe hepatic impairment subjects or clinically significant abnormal sodium and potassium levels, as determined by the Investigator (or designee), at Screening or Check-in (Day 1). Use or intended use of any medications/products known to alter drug absorption, metabolism, or elimination processes. Use of any strong inhibitors or inducers of cytochrome P450 (CYP)2C9 or CYP3A4/5, or inhibitors of CYP3A4 within 30 days prior to first dose administration (Day 1). Alcohol consumption of > 21 units per week for males and > 14 units for females. Positive urine drug screen Positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) test at Screening and Check-in (Day -1), history of hospitalization for coronavirus disease-2019 (COVID-19), or history of use of oxygen due to COVID-19. Note that previous COVID-19 infection alone is not exclusionary and vaccination against SARS-CoV-2 is allowed but must be documented.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Director: Sagimet Biosciences Inc.
Phone
650-561-8675
Email
sitecontact@sagimet.com
Facility Information:
Facility Name
Thomas C. Marbury
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Individual Site Status
Recruiting
Facility Name
Eric J. Lawitz, MD
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Individual Site Status
Recruiting
Facility Name
Geza Lakner
City
Kistarcsa
ZIP/Postal Code
H-2143
Country
Hungary
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Phase I Pharmacokinetic Study of TVB-2640 (Denifanstat) in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Subjects With Normal Hepatic Function

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