A Research Study of the Effect of Etavopivat on Other Drugs in Healthy Participants

An Open-Label, Fixed-Sequence Study to Evaluate the Effect of Etavopivat on the Single-Dose Pharmacokinetics of Midazolam, Digoxin, Rosuvastatin, Pitavastatin, and Metformin in Healthy Adult Participants

The study aims to test if a new medicine called etavopivat potentially affects other medicines in healthy participants. The purpose of the study is to investigate whether the use of etavopivat affects the breakdown and metabolism of commonly used medicines in the body. During the study, participants will receive etavopivat and five different medicines that are already approved and available on the market, and which can be prescribed by doctors. These marketed medicines are called substrate drugs and they are: digoxin, pitavastatin, metformin, midazolam, and rosuvastatin. During a period of the study, participants will take 2 tablets of etavopivat daily for 10 consecutive days. The study will last for about 34 to 64 days.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers Sickle Cell Disease, Thalassemia
• Intervention / Treatment: Drug: Digoxin; Drug: Pitavastatin; Drug: Metformin; Drug: Midazolam; Drug: Rosuvastatin; Drug: Etavopivat

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • ICON-Salt Lake City

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Body mass index (BMI) between 18.5 and 29.9 kilograms per square meter (kg/m^2) (both inclusive) at screening.
• Body weight greater than (>) 50.0 kg at screening.
• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Exclusion Criteria:

• Known or suspected hypersensitivity to study interventions or related products.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive method.
• Exposure to an investigational medicinal product within 30 days or 5 half-lives of the investigational medicinal product (if known), whichever is longer, before screening.
• Participant is unable to refrain from or anticipates the use of any drug known to be a moderate or strong inhibitor or inducer of uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes, CYP3A4, CYP2C9, MATE1, OATP1B1/1B3, BCRP, OCT2, or P-gp, including St. John's Wort for 28 days prior to dosing and throughout the study.
• Use of any medication with unknown or unspecified content within 90 days before screening.
• Use of or intent to use prescription medicinal products or non-prescription drugs (including vitamins and herbal supplements) within 14 days prior to dosing and throughout the study, as declared by the participant, except for:
• Adequate contraceptive methods.
• Hormone replacement therapy (HRT) (for menopausal females).
• Over-the-counter topical medications known to not reach systemic circulation.
• Occasional use of acetaminophen up to 2 grams (g) (4 x 0.5 g) daily.
• Not able or not willing to adhere to study procedures, including:
• Eating the food provided in the study.
• Refraining from ingesting food or drinks that are not allowed during the study.
• Swallowing tablets.
• Abstaining from concomitant medication not allowed during the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1: digoxin+pitavastatin+metformin; Participants will receive a single dose of oral digoxin, pitavastatin and metformin.	Drug: Digoxin; Participants will receive a single dose of digoxin orally.; Drug: Pitavastatin; Participants will receive a single dose of pitavastatin orally.; Drug: Metformin; Participants will receive a single dose of metformin orally.
Experimental: Period 1: midazolam+rosuvastatin; Participants will receive a single dose of oral midazolam and rosuvastatin.	Drug: Midazolam; Participants will receive a single dose of midazolam orally.; Drug: Rosuvastatin; Participants will receive a single dose of rosuvastatin orally.
Experimental: Period 2: etavopivat+midazolam; Participants will receive a daily dose of oral etavopivat and single dose of oral midazolam.	Drug: Midazolam; Participants will receive a single dose of midazolam orally.; Drug: Etavopivat; Participants will receive a daily dose of etavopivat orally.
Experimental: Period 2: etavopivat+midazolam+rosuvastatin; Participants will receive a daily dose of oral etavopivat, single dose of oral midazolam and rosuvastatin.	Drug: Midazolam; Participants will receive a single dose of midazolam orally.; Drug: Rosuvastatin; Participants will receive a single dose of rosuvastatin orally.; Drug: Etavopivat; Participants will receive a daily dose of etavopivat orally.
Experimental: Period 2: etavopivat+digoxin+pitavastatin+metformin; Participants will receive a daily dose of oral etavopivat, single dose of oral digoxin, pitavastatin and metformin.	Drug: Digoxin; Participants will receive a single dose of digoxin orally.; Drug: Pitavastatin; Participants will receive a single dose of pitavastatin orally.; Drug: Metformin; Participants will receive a single dose of metformin orally.; Drug: Etavopivat; Participants will receive a daily dose of etavopivat orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax, digoxin, SD: Maximum observed digoxin plasma concentration with and without etavopivat at steady state	Measured as picograms per milliliter (pg/mL).	Day 1 and day 3 after digoxin administration
AUC0-inf, digoxin, SD: Area under the digoxin plasma concentration-time curve from 0 hours and extrapolated to infinity with and without etavopivat at steady state	Measured as hours*picograms per milliliter (h*pg/mL).	Day 1 and day 3 after digoxin administration
Cmax, rosuvastatin, SD: Maximum observed rosuvastatin plasma concentration with and without etavopivat at steady state	Measured as pg/mL.	Day 1 after rosuvastatin administration
AUC0-inf, rosuvastatin, SD: Area under the rosuvastatin plasma concentration-time curve from 0 hours and extrapolated to infinity with and without etavopivat at steady state	Measured as h*pg/mL.	Day 1 after rosuvastatin administration
Cmax, midazolam, SD: Maximum observed midazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as pg/mL.	Day 1 after midazolam administration
AUC0-inf, midazolam, SD: Area under the midazolam plasma concentration-time curve from 0 hours and extrapolated to infinity without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as h*pg/mL.	Day 1 after midazolam administration
Cmax, pitavastatin, SD: Maximum observed pitavastatin plasma concentration with and without etavopivat at steady state	Measured as nanograms per milliliter (ng/mL).	Day 1 and day 3 after pitavastatin administration
AUC0-inf, pitavastatin, SD: Area under the pitavastatin plasma concentration-time curve from 0 hours and extrapolated to infinity with and without etavopivat at steady state	Measured as hours*nanograms per milliliter(h*ng/mL).	Day 1 and day 3 after pitavastatin administration
Cmax, metformin, SD: Maximum observed metformin plasma concentration with and without etavopivat at steady state	Measured as ng/mL.	Day 1 and day 3 after metformin administration
AUC0-inf, metformin, SD: Area under the metformin plasma concentration-time curve from 0 hours and extrapolated to infinity with and without etavopivat at steady state	Measured as h*ng/mL.	Day 1 and day 3 after metformin administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-last, digoxin, SD: Area under the digoxin plasma concentration-time curve from 0 hours to the last quantifiable concentration with and without etavopivat at steady state	Measured as h*pg/mL.	Day 1 and day 3 after digoxin administration
t1/2, digoxin, SD: Terminal half-life for digoxin with and without etavopivat at steady state	Measured as hours.	Day 1 and day 3 after digoxin administration
tmax, digoxin, SD: Time to maximum observed digoxin plasma concentration with and without etavopivat at steady state	Measured as hours.	Day 1 and day 3 after digoxin administration
CL/Fdigoxin, SD: Apparent plasma clearance of digoxin with and without etavopivat at steady state	Measured as liters per hour (L/h).	Day 1 and day 3 after digoxin administration
Vz/Fdigoxin, SD: Apparent volume of distribution of digoxin with and without etavopivat at steady state based on plasma concentration values	Measured as liters (L).	Day 1 and day 3 after digoxin administration
AUC0-last, rosuvastatin, SD: Area under the rosuvastatin plasma concentration-time curve from 0 hours to the last quantifiable concentration with and without etavopivat at steady state	Measured as h*pg/mL.	Day 1 after rosuvastatin administration
t1/2, rosuvastatin, SD: Terminal half-life for rosuvastatin with and without etavopivat at steady state	Measured as hours.	Day 1 after rosuvastatin administration
tmax, rosuvastatin, SD: Time to maximum observed rosuvastatin plasma concentration with and without etavopivat at steady state	Measured as hours.	Day 1 after rosuvastatin administration
CL/Frosuvastatin, SD: Apparent plasma clearance of rosuvastatin with and without etavopivat at steady state	Measured as L/h.	Day 1 after rosuvastatin administration
Vz/Frosuvastatin, SD: Apparent volume of distribution of rosuvastatin with and without etavopivat at steady state based on plasma concentration values	Measured as L.	Day 1 after rosuvastatin administration
AUC0-last, midazolam, SD: Area under the midazolam plasma concentration-time curve from 0 hours to the last quantifiable concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as h*pg/mL.	Day 1 after midazolam administration
t1/2, midazolam, SD: Terminal half-life for midazolam without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as hours.	Day 1 after midazolam administration
tmax, midazolam, SD: Time to maximum observed midazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as hours.	Day 1 after midazolam administration
CL/Fmidazolam, SD: Apparent plasma clearance of midazolam without etavopivat, with a single dose of etavopivat and with etavopivat at steady state	Measured as L/h.	Day 1 after midazolam administration
Vz/Fmidazolam, SD: Apparent volume of distribution of midazolam without etavopivat, with a single dose of etavopivat and with etavopivat at steady state	Measured as L.	Day 1 after midazolam administration
AUC0-inf, 1-hydroxymidazolam, SD: Area under the midazolam plasma concentration-time curve from 0 hours and extrapolated to infinity without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as h*pg/mL.	Day 1 after midazolam administration
Cmax, 1-hydroxymidazolam, SD: Maximum observed midazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as pg/mL.	Day 1 after midazolam administration
AUC0-last, 1-hydroxymidazolam, SD: Area under the midazolam plasma concentration-time curve from 0 hours to the last quantifiable concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as h*pg/mL.	Day 1 after midazolam administration
t1/2, 1-hydroxymidazolam: Terminal half-life for 1-hydroxymidazolam without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as hours.	Day 1 after midazolam administration
tmax, 1-hydroxymidazolam: Time to maximum observed 1-hydroxymidazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as hours.	Day 1 after midazolam administration
CL/F1-hydroxymidazolam: Apparent plasma clearance of 1-hydroxymidazolam without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as L/h.	Day 1 after midazolam administration
Vz/F1-hydroxymidazolam: Apparent volume of distribution of 1-hydroxymidazolam based on plasma concentration values without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state	Measured as L.	Day 1 after midazolam administration
AUC0-last, pitavastatin, SD: Area under the pitavastatin plasma concentration-time curve from 0 hours to the last quantifiable concentration with and without etavopivat at steady state	Measured as h*ng/mL.	Day 1 and day 3 after pitavastatin administration
t1/2, pitavastatin, SD: Terminal half-life for pitavastatin with and without etavopivat at steady state	Measured as hours.	Day 1 and day 3 after pitavastatin administration
tmax, pitavastatin, SD: Time to maximum observed pitavastatin plasma concentration with and without etavopivat at steady state	Measured as hours.	Day 1 and day 3 after pitavastatin administration
CL/Fpitavastatin, SD: Apparent plasma clearance of pitavastatin with and without etavopivat at steady state	Measured as L/h.	Day 1 and day 3 after pitavastatin administration
Vz/Fpitavastatin, SD: Apparent volume of distribution of pitavastatin with and without etavopivat at steady state based on plasma concentration values	Measured as L.	Day 1 and day 3 after pitavastatin administration
AUC0-last, metformin, SD: Area under the metformin plasma concentration-time curve from 0 hours to the last quantifiable concentration with and without etavopivat at steady state	Measured as h*ng/mL.	Day 1 and day 3 after metformin administration
t1/2, metformin, SD: Terminal half-life for metformin with and without etavopivat at steady state	Measured as hours.	Day 1 and day 3 after metformin administration
tmax, metformin, SD: Time to maximum observed metformin plasma concentration with and without etavopivat at steady state	Measured as hours.	Day 1 and day 3 after metformin administration
CL/Fmetformin, SD: Apparent plasma clearance of metformin with and without etavopivat at steady state	Measured as L/h.	Day 1 and day 3 after metformin administration
Vz/Fmetformin, SD: Apparent volume of distribution of metformin with and without etavopivat at steady state based on plasma concentration values	Measured as L.	Day 1 and day 3 after metformin administration
Aelast, metformin, SD%: Percentage of the metformin excreted into urine from the time of dosing to the collection time of the last measurable concentration with and without etavopivat at steady state	Measured as percentage (%) of the metformin excreted into urine.	Day 1 and day 3 after metformin administration
CLR, metformin, SD: Renal clearance of metformin	Measured as L/h.	Day 1 and day 3 after metformin administration
AUC0-tau, etavopivat: Area under the etavopivat plasma concentration-time curve during one dosing interval at single dose and at steady state	Measured as h*ng/mL.	Day 1 and day 3 after etavopivat administration
AUC0-last etavopivat: Area under the etavopivat plasma concentration-time curve from 0 hours to the last quantifiable concentration at single dose and at steady state	Measured as h*ng/mL.	Day 1 and day 3 after etavopivat administration
Cmax, etavopivat: Maximum observed etavopivat plasma concentration at single dose and at steady state	Measured as ng/mL.	Day 1 and day 3 after etavopivat administration
t1/2, etavopivat: Terminal half-life for etavopivat at single dose and at steady state	Measured as hours.	Day 1 and day 3 after etavopivat administration
tmax, etavopivat: Time to maximum observed etavopivat plasma concentration at single dose and at steady state	Measured as hours.	Day 1 and day 3 after etavopivat administration
V/Fetavopivat: Apparent volume of distribution of etavopivat based on plasma concentration values at single dose and at steady state	Measured as L.	Day 1 and day 3 after etavopivat administration
CL/Fetavopivat: Apparent plasma clearance of etavopivat at single dose and at steady state	Measured as L/h.	Day 1 and day 3 after etavopivat administration
C, etavopivat: Observed etavopivat plasma concentration after single and multiple doses	Measured as ng/mL.	From day 1 to day 4 after administration of etavopivat
Number of adverse events (AEs)	Measured as count of events.	From first dose (day 1) until end of study (day 32)

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): February 6, 2025
• Primary Completion (Actual): May 27, 2025
• Study Completion (Actual): May 27, 2025

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): February 7, 2025

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 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; Thalassemia; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Carbohydrates; Polycyclic Compounds; Glycosides; Amides; Pyrimidines; Steroids; Fused-Ring Compounds; Hydrocarbons, Halogenated; Benzazepines; Biguanides; Guanidines; Amidines; Sulfonamides; Sulfones; Benzodiazepines; Fluorobenzenes; Hydrocarbons, Fluorinated; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Rosuvastatin Calcium; Midazolam; Digoxin; Metformin; pitavastatin
• Other Study ID Numbers: NN7535-7976; U1111-1309-3456 (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