A Research Study on Etavopivat in Participants With and Without Liver Disease

A Multi-centre, Open-label, Parallel-group Study Investigating the Pharmacokinetics, Safety and Tolerability After a Single Dose of Oral Etavopivat in Participants With Mild, Moderate or Severe Hepatic Impairment Compared to Participants With Normal Hepatic Function

The study investigates an investigational drug called etavopivat in participants with hepatic impairments and participants with normal hepatic function (matched controls). During the study, all participants will be given a single oral dose of etavopivat. All participants will take the etavopivat orally together with water. After dosing, the study will last for 7 to 9 days.

Study Overview

• Status: Completed
• Conditions: Liver Diseases
• Intervention / Treatment: Drug: Etavopivat

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92866
      • Cure Clinical Research LLC
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
    • Orlando, Florida, United States, 32806
      • Orlando Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78215
      • Amer. Rrsch Corp-TX Liver Inst

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female.
• Age 18 years or above at the time of signing the informed consent.
• Body mass index (BMI) between 18.5 and 42.0 kilogram per meter^2 (kg/m^2) (both inclusive) at screening.
• Body weight greater than or equal to (>=) 40.0 kilogram (kg) at screening.

Specific inclusion criteria only for participants with hepatic impairment:

• Participants with chronic (above 6 months), stable (no significant deterioration in hepatic function in last 2 months as determined by the investigator) hepatic impairment classified as Child-Pugh class A, B or C, as assessed by the investigator and which is confirmed and documented by medical history, physical examination and at least one of the following: hepatic ultrasound, computerised axial tomography (CT) scan, magnetic resonance imaging (MRI), and/or liver biopsy.
• Participants must be on a stable dose of medication and/or treatment regimen (e.g., no expectations of new medications nor changes to current medications within 14 days of dosing).

Specific inclusion criterion only for participants with normal hepatic function:

- Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram (ECG), and laboratory safety tests performed during screening visit, as judged by the investigator.

Exclusion Criteria:

• Known or suspected hypersensitivity to study intervention or related products.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive methods.
• Participation (i.e., signed informed consent) in any interventional clinical study within 30 days or 5 times the half-life of the previous investigational medical product (IMP) (if known), whichever is longer, before screening.
• Any disorder, unwillingness or inability, except for conditions associated with hepatic impairment in the group of participants with compromised hepatic function, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.

• Participant is unable to refrain from or anticipates the use of, for 7 days prior to dosing and throughout the study, any drug known to be:

  • an inhibitor of uridine 5'-diphospho-glucuronosyltransferase (UGT) 2B7,
  • a strong inhibitor of cytochrome P450 (CYP)3A4 or CYP2C9,
  • a potent inhibitor of permeability glycoprotein (P-gp).

• Participant is unable to refrain from or anticipates the use of, for 28 days prior to dosing and throughout the study, any drug known to be:

  • an inducer of UGT2B7,
  • a strong or moderate inducer of CYP3A4, including St. John's Wort,
  • a strong inducer of CYP2C9,
  • a potent inducer of P-gp.
• Participant is unable to refrain from or anticipates the use of any medications or substances prohibited in the study.

Specific exclusion criterion only for participants with hepatic impairment:

- Clinical signs of an acute hepatitis (viral as well as non-viral) or positive tests of hepatitis B virus surface antigen (HBsAg) (unless hepatitis B virus titre is negative) or antibody tests of hepatitis C virus (HCV-Ab) (unless negative polymerase chain reaction [PCR] for hepatitis C virus).

Specific exclusion criteria only for participants with normal hepatic function:

• Diagnostic test results positive for hepatitis B or hepatitis C infection.
• History of diabetes mellitus or glycated haemoglobin (HbA1c) greater than or equal to 5 percent (48 millimoles per mole [mmol/mol]) at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild hepatic impairment: Etavopivat dose 2; Participants will receive a single dose of oral etavopivat.	Drug: Etavopivat; Participants will receive a single dose of etavopivat orally.
Experimental: Moderate hepatic impairment: Etavopivat dose 2; Participants will receive a single dose of oral etavopivat.	Drug: Etavopivat; Participants will receive a single dose of etavopivat orally.
Experimental: Healthy matched controls: Etavopivat dose 2; Participants will receive a single dose of oral etavopivat.	Drug: Etavopivat; Participants will receive a single dose of etavopivat orally.
Experimental: Severe hepatic impairment: Etavopivat dose 1; Participants will receive a single dose of oral etavopivat.	Drug: Etavopivat; Participants will receive a single dose of etavopivat orally.
Experimental: Healthy matched controls: Etavopivat dose 1; Participants will receive a single dose of oral etavopivat.	Drug: Etavopivat; Participants will receive a single dose of etavopivat orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the etavopivat plasma concentration-time curve from 0 hours and extrapolated to infinity after a single dose (AUC0-inf, etavopivat)	Measured in hours*nanogram per milliter (h*ng/mL).	From IMP administration on day 1 to completion of the end of study visit (day 9)
Maximum observed etavopivat plasma concentration after a single dose (Cmax, etavopivat)	Measured in nanogram per milliter (ng/mL).	From IMP administration on day 1 to completion of the end of study visit (day 9)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the etavopivat plasma concentration-time curve from 0 hours to the last quantifiable concentration after a single dose (AUC0-last, etavopivat)	Measured in h*ng/mL.	From IMP administration on day 1 to completion of the end of study visit (day 9)
Time to maximum observed etavopivat plasma concentration after a single dose (tmax, etavopivat)	Measured in hours.	From IMP administration on day 1 to completion of the end of study visit (day 9)
Terminal half-life for etavopivat after a single dose (t1/2, etavopivat)	Measured in hours.	From IMP administration on day 1 to completion of the end of study visit (day 9)
Apparent plasma clearance of etavopivat after a single dose (CL/Fetavopivat)	Measured in liter per hour (L/h).	From IMP administration on day 1 to completion of the end of study visit (day 9)
Apparent volume of distribution of etavopivat after a single dose based on plasma concentration values (Vz/Fetavopivat)	Measured in liter (L).	From IMP administration on day 1 to completion of the end of study visit (day 9)
Number of adverse events (AEs)	Measured as count of events.	From IMP administration on day 1 to completion of the end of study visit (day 9)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2024
• Primary Completion (Actual): August 1, 2025
• Study Completion (Actual): August 1, 2025

Study Registration Dates

• First Submitted: March 22, 2024
• First Submitted That Met QC Criteria: March 22, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: NN7535-7703; U1111-1289-2466 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No