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

NCT05835180 | Completed Phase 1 FDA Drug

• 1 other identifier: SB2640-CLIN-009
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 3

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.

Conditions

Non-alcoholic Steatohepatitis; Hepatic Impairment; Cirrhosis

Keywords

NASH; Hepatic impairment; Cirrhosis

Outcome Measures

Primary Outcomes (5)

• Total TVB-2640 plasma concentration-time (AUC) at steady state

  Total TVB-2640 plasma concentration-time curve during a dosing interval at steady-state

  Day 4

• Unbound TVB-2640 plasma concentration-time (AUC) at steady state

  Unbound TVB-2640 plasma concentration-time curve during a dosing interval at steady-state

  Day 4

• Maximum plasma concentration (Cmax) for total TVB-2640 at steady state

  Day 4

• Maximum plasma concentration (Cmax) for unbound TVB-2640 at steady state

  Day 4

• incidence and severity of AEs

  Screening to Day 7

Study Arms (4)

TVB-2640 50 mg - normal hepatic function

EXPERIMENTAL

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

Drug: TVB-2640 - 50 mg

TVB-2640 50 mg - mild hepatic function

EXPERIMENTAL

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

Drug: TVB-2640 - 50 mg

TVB-2640 50 mg - moderate hepatic function

EXPERIMENTAL

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

Drug: TVB-2640 - 50 mg

TVB-2640 50 mg - severe hepatic function

EXPERIMENTAL

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

Drug: TVB-2640 - 50 mg

Interventions

TVB-2640 - 50 mg DRUG

TVB-2640 -50 mg administered orally once daily

TVB-2640 50 mg - mild hepatic function; TVB-2640 50 mg - moderate hepatic function; TVB-2640 50 mg - normal hepatic function; TVB-2640 50 mg - severe hepatic function

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sagimet Biosciences Inc.: lead

Study Sites (3)

Thomas C. Marbury

Orlando, Florida, 32809, United States

Location

Eric J. Lawitz, MD

San Antonio, Texas, 78215, United States

Location

Geza Lakner

Kistarcsa, H-2143, Hungary

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fibrosis

Interventions

TVB-2640

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2023
• First Posted: April 28, 2023
• Study Start: May 1, 2023
• Primary Completion: December 18, 2023
• Study Completion: December 18, 2023
• Last Updated: December 26, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1); US (2)