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

Liver Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06336018
• Other study ID #: NN7535-7703
• Secondary ID: U1111-1289-2466
• Status: Recruiting
• Phase: Phase 1
• Start date: June 4, 2024
• Est. completion date: September 4, 2025

Study information

• Verified date: June 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: September 4, 2025
• Est. primary completion date: September 4, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Liver Diseases

Intervention

Drug:
• Etavopivat
Participants will receive a single dose of etavopivat orally.

Locations

Country	Name	City	State
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Amer. Rrsch Corp-TX Liver Inst	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)