Clinical trial NCT06336018: A Research Study on Etavopivat in Participants With and Without Liver Disease
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Liver Diseases
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2024-03-28
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area under the etavopivat plasma concentration-time curve from 0 hours and extrapolated to infinity after a single dose (AUC0-inf, etavopivat)
timeFrame: From IMP administration on day 1 to completion of the end of study visit (day 9)
measure: Maximum observed etavopivat plasma concentration after a single dose (Cmax, etavopivat)
timeFrame: From IMP administration on day 1 to completion of the end of study visit (day 9)
Secondary outcomes:
measure: Area under the etavopivat plasma concentration-time curve from 0 hours to the last quantifiable concentration after a single dose (AUC0-last, etavopivat)
timeFrame: From IMP administration on day 1 to completion of the end of study visit (day 9)
measure: Time to maximum observed etavopivat plasma concentration after a single dose (tmax, etavopivat)
timeFrame: From IMP administration on day 1 to completion of the end of study visit (day 9)
measure: Terminal half-life for etavopivat after a single dose (t1/2, etavopivat)
timeFrame: From IMP administration on day 1 to completion of the end of study visit (day 9)
measure: Apparent plasma clearance of etavopivat after a single dose (CL/Fetavopivat)
timeFrame: From IMP administration on day 1 to completion of the end of study visit (day 9)
measure: Apparent volume of distribution of etavopivat after a single dose based on plasma concentration values (Vz/Fetavopivat)
timeFrame: From IMP administration on day 1 to completion of the end of study visit (day 9)
measure: Number of adverse events (AEs)
timeFrame: From IMP administration on day 1 to completion of the end of study visit (day 9)
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: San Antonio
country: United States
facility: Amer. Rrsch Corp-TX Liver Inst
state: Texas
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: