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

NCT06813924 | Completed Phase 1 FDA Drug

• 2 other identifiers: NN7535-7976U1111-1309-3456
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers Sickle Cell Disease, Thalassemia

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (43)

• 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

  Day 1 and day 3 after digoxin administration

• t1/2, digoxin, SD: Terminal half-life for digoxin with and without etavopivat at steady state

  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

  Day 1 and day 3 after digoxin administration

• CL/Fdigoxin, SD: Apparent plasma clearance of digoxin with and without etavopivat at steady state

  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

  Day 1 and day 3 after digoxin administration

Study Arms (5)

Period 1: digoxin+pitavastatin+metformin

EXPERIMENTAL

Participants will receive a single dose of oral digoxin, pitavastatin and metformin.

Drug: Digoxin; Drug: Pitavastatin; Drug: Metformin

Period 1: midazolam+rosuvastatin

EXPERIMENTAL

Participants will receive a single dose of oral midazolam and rosuvastatin.

Drug: Midazolam; Drug: Rosuvastatin

Period 2: etavopivat+midazolam

EXPERIMENTAL

Participants will receive a daily dose of oral etavopivat and single dose of oral midazolam.

Drug: Etavopivat; Drug: Midazolam

Period 2: etavopivat+midazolam+rosuvastatin

EXPERIMENTAL

Participants will receive a daily dose of oral etavopivat, single dose of oral midazolam and rosuvastatin.

Drug: Etavopivat; Drug: Midazolam; Drug: Rosuvastatin

Period 2: etavopivat+digoxin+pitavastatin+metformin

EXPERIMENTAL

Participants will receive a daily dose of oral etavopivat, single dose of oral digoxin, pitavastatin and metformin.

Drug: Etavopivat; Drug: Digoxin; Drug: Pitavastatin; Drug: Metformin

Interventions

Etavopivat DRUG

Participants will receive a daily dose of etavopivat orally.

Period 2: etavopivat+digoxin+pitavastatin+metformin; Period 2: etavopivat+midazolam; Period 2: etavopivat+midazolam+rosuvastatin

Digoxin DRUG

Participants will receive a single dose of digoxin orally.

Period 1: digoxin+pitavastatin+metformin; Period 2: etavopivat+digoxin+pitavastatin+metformin

Pitavastatin DRUG

Participants will receive a single dose of pitavastatin orally.

Period 1: digoxin+pitavastatin+metformin; Period 2: etavopivat+digoxin+pitavastatin+metformin

Metformin DRUG

Participants will receive a single dose of metformin orally.

Period 1: digoxin+pitavastatin+metformin; Period 2: etavopivat+digoxin+pitavastatin+metformin

Midazolam DRUG

Participants will receive a single dose of midazolam orally.

Period 1: midazolam+rosuvastatin; Period 2: etavopivat+midazolam; Period 2: etavopivat+midazolam+rosuvastatin

Rosuvastatin DRUG

Participants will receive a single dose of rosuvastatin orally.

Period 1: midazolam+rosuvastatin; Period 2: etavopivat+midazolam+rosuvastatin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (1)

ICON-Salt Lake City

Salt Lake City, Utah, 84124, United States

Location

MeSH Terms

Conditions

Thalassemia

Interventions

Digoxin; pitavastatin; Metformin; Midazolam; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Biguanides; Guanidines; Amidines; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 7, 2025
• Study Start: February 6, 2025
• Primary Completion: May 27, 2025
• Study Completion: May 27, 2025
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)