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

Novo Nordisk

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers Sickle Cell Disease, Thalassemia

Treatments: Drug: Metformin; Drug: Digoxin; Drug: Etavopivat; Drug: Pitavastatin; Drug: Rosuvastatin; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT06813924

U1111-1309-3456 (Other Identifier)

NN7535-7976

Details and patient eligibility

About

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.

Enrollment: 37 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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37 participants in 5 patient groups

Period 1: digoxin+pitavastatin+metformin

Experimental group

Description:

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

Treatment:

Drug: Pitavastatin

Drug: Digoxin

Drug: Metformin

Period 1: midazolam+rosuvastatin

Experimental group

Description:

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

Treatment:

Drug: Midazolam

Drug: Rosuvastatin

Period 2: etavopivat+midazolam

Experimental group

Description:

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

Treatment:

Drug: Midazolam

Drug: Etavopivat

Period 2: etavopivat+midazolam+rosuvastatin

Experimental group

Description:

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

Treatment:

Drug: Midazolam

Drug: Rosuvastatin

Drug: Etavopivat

Period 2: etavopivat+digoxin+pitavastatin+metformin

Experimental group

Description:

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

Treatment:

Drug: Pitavastatin

Drug: Etavopivat

Drug: Digoxin

Drug: Metformin