A Study on the Effect of Etavopivat on Heart Rhythm in Healthy Participants

A Study to Assess the Effect of Etavopivat on Cardiac Repolarisation in Healthy Participants

Novo Nordisk is developing a new study medicine, Etavopivat, to treat individuals with sickle cell disease (SCD). The purpose of the study is to determine the effect of Etavopivat on the electrical activity of the heart in healthy participants. The study comprises two parts: Part A and Part B. Part A investigates the safety of a high dose of Etavopivat. In this phase, participants will receive either a single dose of Etavopivat or a placebo. Which treatment the participant gets is decided by chance. In Part B, participants will get four different treatments on four different occasions: Etavopivat in 2 different doses (the new medicine that cannot be prescribed), a dummy medicine (placebo), and an already approved medicine (moxifloxacin). The order of the 4 study medicines is decided by chance. There will be a break of 7 days between each treatment. For Part A, the study duration will be from 10 to 36 days, and for Part B, the study duration will be from 27 to 53 days.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Sickle Cell Disease; Thalassemia
• Intervention / Treatment: Drug: Etavopivat; Drug: Placebo; Drug: Moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • PAREXEL Intl - EPCU-Baltimore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female.
• Aged 18-55 years (both inclusive) at the time of signing informed consent.
• Body mass index (BMI) between 18.0 and 32.0 kilograms per square meter (kg/m^2) (both inclusive) at screening.
• Body weight above 40.0 kg at screening.
• Considered to be generally healthy based on the medical history, physical examination and the results of vital signs, electrocardiogram (ECG) and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive methods, as defined in Appendix 4, Section 10.4.
• Current participation (i.e., signed informed consent) in any other interventional clinical study.
• Exposure to an investigational medicinal product within 30 days or 5 half-lives of the investigational medicinal product (IMP) (if known), whichever is longer, before screening.
• Any condition which in the investigator's opinion might jeopardise the participant's safety or compliance with the protocol.
• Second or 3rd degree atrioventricular-block, prolongation of the QRS complex over 120 milliseconds (ms)., or of the corrected QT interval using the Fredericia formula (QTcF) over 450 ms for males and 470 ms for females, prominent U waves, or any other clinically significant abnormal ECG results or changes that make ECGs unsuitable for QT evaluations as judged by the investigator, at screening.
• Use of tobacco and nicotine products, defined as any of the below:
• Has used any product containing tobacco or nicotine within 90 days prior to screening.
• Unable or unwilling to refrain from the use of any product containing tobacco or nicotine throughout the study.
• Positive nicotine test at screening.
• Participant is unable to refrain from or anticipates the use of antacids, iron, or any drug known to be a moderate or strong inhibitor or inducer of uridine 5'-diphosphoglucuronosyltransferase (UGT) enzymes, cytochrome P450 (CYP) 3A4, CYP2C9 or permeability glycoprotein (P-gp), including St. John's Wort, for 28 days prior to dosing and throughout the study (Section 6.8).
• Participant is unable to refrain from or anticipate the use of any medications or substances prohibited in the study (Sections 5.3, 5.5 and 6.8).

A minimum of 20% African-American participants will be included in each part of this study.

Efforts will be made to include at least 40 percentage (%) of each sex into each part of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A- Etavopivat; Participants will receive a single dose of etavopivat.	Drug: Etavopivat; Etavopivat will be administered orally.
Placebo Comparator: Part A- Placebo; Participants will receive a single dose of placebo.	Drug: Placebo; Placebo matching Etavopivat will be administered orally.
Experimental: Part B- Etavopivat; Participants will receive a single dose of etavopivat.	Drug: Etavopivat; Etavopivat will be administered orally.
Other: Part B- Moxifloxacin; Participants will receive a single dose of moxifloxacin.	Drug: Moxifloxacin; Moxifloxacin will be administered orally.
Placebo Comparator: Part B- Placebo; Participants will receive a single dose of placebo.	Drug: Placebo; Placebo matching Etavopivat will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of treatment-emergent adverse events (AEs)	Measured as count of events.	From dosing (Day 1) until end of study (Day 8)
Part B: Change from baseline in Fridericia heart rate corrected QT interval (ΔQTcF) for etavopivat	Measured as milliseconds.	From pre-dose to post etavopivat/ etavopivat placebo dose on day 1 to day 23

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of treatment-emergent clinically significant abnormal findings in electrocardiogram (ECGs)	Measured as count of treatment-emergent clinically significant abnormal findings in ECGs.	From dosing (Day 1) until end of study (Day 8)
Parts A and B: Cmax,etavopivat- Maximum observed etavopivat plasma concentration after a single dose	Measured as nanograms per milliliter (ng/mL).	Day 1 (Part B)/ From day 1 to day 5 (Part A) after investigational medicinal product (IMP) administration
Parts A and B: AUC0-last,etavopivat- Area under the etavopivat plasma concentration-time curve from 0 hours to the time of last quantifiable concentration	Measured as hours*nanograms per milliliter (h*ng/mL).	Day 1 (Part B)/ From day 1 to day 5 (Part A) after IMP administration
Parts A and B: AUC0-inf,etavopivat- Area under the etavopivat plasma concentration-time curve from 0 hours and extrapolated to infinity after a single dose	Measured as h*ng/mL.	Day 1 (Part B)/ From day 1 to day 5 (Part A) after IMP administration
Parts A and B: tmax,etavopivat- Time to maximum observed etavopivat plasma concentration after a single dose	Measured as hours.	Day 1 (Part B)/ From day 1 to day 5 (Part A) after IMP administration
Parts A and B: t½ etavopivat- Terminal half-life for etavopivat after a single dose	Measured as hours.	Day 1 (Part B)/ From day 1 to day 5 (Part A) after IMP administration
Parts A and B: CL/F etavopivat- Apparent plasma clearance of etavopivat after a single dose	Measured as liters per hour (L/h).	Day 1 (Part B)/ From day 1 to day 5 (Part A) after IMP administration
Parts A and B: Vz/F etavopivat- Apparent volume of distribution of etavopivat after a single dose based on plasma concentration values	Measured as liters (L).	Day 1 (Part B)/ From day 1 to day 5 (Part A) after IMP administration
Part B: ΔQTcF for moxifloxacin	Measured as milliseconds.	From pre-dose to post moxifloxacin dose on day 1 to day 23
Part B: Frequency of treatment emergent changes of ECG morphology	Measured as count of treatment emergent changes of ECG morphology.	From pre-dose to post etavopivat/ etavopivat placebo dose on day 1 to day 23
Part B: Frequency of treatment emergent changes of ECG morphology	Measured as count of treatment emergent changes of ECG morphology.	From pre-dose to post moxifloxacin dose on day 1 to day 23
Part B: ΔQTcF for etavopivat	Measured as milliseconds.	From pre-dose to post etavopivat/etavopivat placebo dose on day 1 to day 23
Part B: Change from baseline in heart rate (ΔHR). Categorical outliers for HR	Measured as milliseconds.	From pre-dose to post etavopivat/ etavopivat placebo dose on day 1 to day 23
Part B: Change from baseline in PR interval (ΔPR). Categorical outliers for PR	Measured as milliseconds.	From pre-dose to post etavopivat/ etavopivat placebo dose on day 1 to day 23
Part B: Change from baseline in QRS complex duration (ΔQRS). Categorical outliers for QRS	Measured as milliseconds.	From pre-dose to post etavopivat/ etavopivat placebo dose on day 1 to day 23
Part B: Change from baseline in ΔHR. Categorical outliers for HR	Measured as milliseconds.	From pre-dose to post moxifloxacin dose on day 1 to day 23
Part B: Change from baseline in ΔPR. Categorical outliers for PR	Measured as milliseconds.	From pre-dose to post moxifloxacin dose on day 1 to day 23
Part B: Change from baseline in ΔQRS. Categorical outliers for QRS	Measured as milliseconds.	From pre-dose to post moxifloxacin dose on day 1 to day 23

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): June 9, 2025
• Primary Completion (Actual): September 12, 2025
• Study Completion (Actual): September 22, 2025

Study Registration Dates

• First Submitted: June 8, 2025
• First Submitted That Met QC Criteria: June 8, 2025
• First Posted (Actual): June 15, 2025

Study Record Updates

• Last Update Posted (Estimated): January 2, 2026
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Thalassemia; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Moxifloxacin
• Other Study ID Numbers: NN7535-7975; U1111-1314-5780 (Other Identifier: Universal Trial Number)

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