Clinical trial NCT06813924: A Research Study of the Effect of Etavopivat on Other Drugs in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers Sickle Cell Disease, Thalassemia
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2025-02-07
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Cmax, digoxin, SD: Maximum observed digoxin plasma concentration with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after digoxin administration
measure: 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
timeFrame: Day 1 and day 3 after digoxin administration
measure: Cmax, rosuvastatin, SD: Maximum observed rosuvastatin plasma concentration with and without etavopivat at steady state
timeFrame: Day 1 after rosuvastatin administration
measure: 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
timeFrame: Day 1 after rosuvastatin administration
measure: Cmax, midazolam, SD: Maximum observed midazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state
timeFrame: Day 1 after midazolam administration
measure: 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
timeFrame: Day 1 after midazolam administration
measure: Cmax, pitavastatin, SD: Maximum observed pitavastatin plasma concentration with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after pitavastatin administration
measure: 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
timeFrame: Day 1 and day 3 after pitavastatin administration
measure: Cmax, metformin, SD: Maximum observed metformin plasma concentration with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after metformin administration
measure: 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
timeFrame: Day 1 and day 3 after metformin administration
Secondary outcomes:
measure: 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
timeFrame: Day 1 and day 3 after digoxin administration
measure: t1/2, digoxin, SD: Terminal half-life for digoxin with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after digoxin administration
measure: tmax, digoxin, SD: Time to maximum observed digoxin plasma concentration with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after digoxin administration
measure: CL/Fdigoxin, SD: Apparent plasma clearance of digoxin with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after digoxin administration
measure: Vz/Fdigoxin, SD: Apparent volume of distribution of digoxin with and without etavopivat at steady state based on plasma concentration values
timeFrame: Day 1 and day 3 after digoxin administration
measure: 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
timeFrame: Day 1 after rosuvastatin administration
measure: t1/2, rosuvastatin, SD: Terminal half-life for rosuvastatin with and without etavopivat at steady state
timeFrame: Day 1 after rosuvastatin administration
measure: tmax, rosuvastatin, SD: Time to maximum observed rosuvastatin plasma concentration with and without etavopivat at steady state
timeFrame: Day 1 after rosuvastatin administration
measure: CL/Frosuvastatin, SD: Apparent plasma clearance of rosuvastatin with and without etavopivat at steady state
timeFrame: Day 1 after rosuvastatin administration
measure: Vz/Frosuvastatin, SD: Apparent volume of distribution of rosuvastatin with and without etavopivat at steady state based on plasma concentration values
timeFrame: Day 1 after rosuvastatin administration
measure: 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
timeFrame: Day 1 after midazolam administration
measure: t1/2, midazolam, SD: Terminal half-life for midazolam without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state
timeFrame: Day 1 after midazolam administration
measure: tmax, midazolam, SD: Time to maximum observed midazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state
timeFrame: Day 1 after midazolam administration
measure: CL/Fmidazolam, SD: Apparent plasma clearance of midazolam without etavopivat, with a single dose of etavopivat and with etavopivat at steady state
timeFrame: Day 1 after midazolam administration
measure: Vz/Fmidazolam, SD: Apparent volume of distribution of midazolam without etavopivat, with a single dose of etavopivat and with etavopivat at steady state
timeFrame: Day 1 after midazolam administration
measure: 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
timeFrame: Day 1 after midazolam administration
measure: Cmax, 1-hydroxymidazolam, SD: Maximum observed midazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state
timeFrame: Day 1 after midazolam administration
measure: 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
timeFrame: Day 1 after midazolam administration
measure: t1/2, 1-hydroxymidazolam: Terminal half-life for 1-hydroxymidazolam without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state
timeFrame: Day 1 after midazolam administration
measure: 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
timeFrame: Day 1 after midazolam administration
measure: CL/F1-hydroxymidazolam: Apparent plasma clearance of 1-hydroxymidazolam without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state
timeFrame: Day 1 after midazolam administration
measure: 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
timeFrame: Day 1 after midazolam administration
measure: 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
timeFrame: Day 1 and day 3 after pitavastatin administration
measure: t1/2, pitavastatin, SD: Terminal half-life for pitavastatin with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after pitavastatin administration
measure: tmax, pitavastatin, SD: Time to maximum observed pitavastatin plasma concentration with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after pitavastatin administration
measure: CL/Fpitavastatin, SD: Apparent plasma clearance of pitavastatin with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after pitavastatin administration
measure: Vz/Fpitavastatin, SD: Apparent volume of distribution of pitavastatin with and without etavopivat at steady state based on plasma concentration values
timeFrame: Day 1 and day 3 after pitavastatin administration
measure: 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
timeFrame: Day 1 and day 3 after metformin administration
measure: t1/2, metformin, SD: Terminal half-life for metformin with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after metformin administration
measure: tmax, metformin, SD: Time to maximum observed metformin plasma concentration with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after metformin administration
measure: CL/Fmetformin, SD: Apparent plasma clearance of metformin with and without etavopivat at steady state
timeFrame: Day 1 and day 3 after metformin administration
measure: Vz/Fmetformin, SD: Apparent volume of distribution of metformin with and without etavopivat at steady state based on plasma concentration values
timeFrame: Day 1 and day 3 after metformin administration
measure: 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
timeFrame: Day 1 and day 3 after metformin administration
measure: CLR, metformin, SD: Renal clearance of metformin
timeFrame: Day 1 and day 3 after metformin administration
measure: AUC0-tau, etavopivat: Area under the etavopivat plasma concentration-time curve during one dosing interval at single dose and at steady state
timeFrame: Day 1 and day 3 after etavopivat administration
measure: 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
timeFrame: Day 1 and day 3 after etavopivat administration
measure: Cmax, etavopivat: Maximum observed etavopivat plasma concentration at single dose and at steady state
timeFrame: Day 1 and day 3 after etavopivat administration
measure: t1/2, etavopivat: Terminal half-life for etavopivat at single dose and at steady state
timeFrame: Day 1 and day 3 after etavopivat administration
measure: tmax, etavopivat: Time to maximum observed etavopivat plasma concentration at single dose and at steady state
timeFrame: Day 1 and day 3 after etavopivat administration
measure: V/Fetavopivat: Apparent volume of distribution of etavopivat based on plasma concentration values at single dose and at steady state
timeFrame: Day 1 and day 3 after etavopivat administration
measure: CL/Fetavopivat: Apparent plasma clearance of etavopivat at single dose and at steady state
timeFrame: Day 1 and day 3 after etavopivat administration
measure: C, etavopivat: Observed etavopivat plasma concentration after single and multiple doses
timeFrame: From day 1 to day 4 after administration of etavopivat
measure: Number of adverse events (AEs)
timeFrame: From first dose (day 1) until end of study (day 32)
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: ICON-Salt Lake City
state: Utah
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: