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

Novo Nordisk A/S37 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Volunteers Sickle Cell Disease, Thalassemia

Interventions

Participants will receive a daily dose of etavopivat orally.

DigoxinDRUG

Participants will receive a single dose of digoxin orally.

PitavastatinDRUG

Participants will receive a single dose of pitavastatin orally.

MetforminDRUG

Participants will receive a single dose of metformin orally.

MidazolamDRUG

Participants will receive a single dose of midazolam orally.

RosuvastatinDRUG

Participants will receive a single dose of rosuvastatin orally.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

ICON-Salt Lake City

Salt Lake City, Utah, United States

Outcomes

Primary Outcomes

Cmax, digoxin, SD: Maximum observed digoxin plasma concentration with and without etavopivat at steady state

Measured as picograms per milliliter (pg/mL).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: Day 1 and day 3 after metformin administration

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: Day 1 after rosuvastatin administration

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

Measured as hours.

Time frame: Day 1 after rosuvastatin administration

tmax, rosuvastatin, SD: Time to maximum observed rosuvastatin plasma concentration with and without etavopivat at steady state

Data from ClinicalTrials.gov

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Time frame: Day 1 after rosuvastatin administration

CL/Frosuvastatin, SD: Apparent plasma clearance of rosuvastatin with and without etavopivat at steady state

Measured as L/h.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Day 1 and day 3 after metformin administration

CLR, metformin, SD: Renal clearance of metformin

Measured as L/h.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Day 1 and day 3 after etavopivat administration

C, etavopivat: Observed etavopivat plasma concentration after single and multiple doses

Measured as ng/mL.

Time frame: From day 1 to day 4 after administration of etavopivat

Number of adverse events (AEs)

Measured as count of events.

Time frame: From first dose (day 1) until end of study (day 32)