Drug-drug Interaction Study of Vorasidenib With Bupropion, Repaglinide, Flurbiprofen, Omeprazole, Midazolam, and Rosuvastatin in Healthy Adult Participants

Servier

Status and phase

Completed

Phase 1

Conditions

Healthy Adult Participants

Treatments

Drug: Flurbiprofen

Drug: Bupropion

Drug: Vorasidenib

Drug: Midazolam

Drug: Omeprazole

Drug: Repaglinide

Drug: Rosuvastatin

Study type

Interventional

Funder types

Industry

Identifiers

NCT07235748

S095032-230

Details and patient eligibility

About

The objective of this study is to evaluate the effect of multiple doses of vorasidenib on single-dose PK of bupropion as an index substrate of CYP2B6, flurbiprofen as an index substrate of CYP2C9, omeprazole as an index substrate of CYP2C19, repaglinide as an index substrate of CYP2C8, midazolam as an index substrate of CYP3A4, and rosuvastatin as a substrate of BCRP in healthy adult participants. The study consists of screening, two treatment periods in-house, and a follow-up period. During the first period, Day 1 through Day 7, participants will receive CYPs and BCRP index substrates alone and during the second treatment period, Day 8 through Day 28, these will be administered in combination with vorasidenib. Participation in the study will be up to 87 days from screening through the follow up period.

Study activities may include blood tests, ECG, vital signs, and a physical examination.

Enrollment

28 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy male or non-pregnant, non-lactating female participants, including women of childbearing potential (WOCBP).
Body mass index (BMI) of 18.0 - 30.0 kg/m² (both inclusive), at Screening.
Body weight of at least 40 kg, at Screening.
Female participants of childbearing potential must use 2 effective methods of birth control, or abstinence from Screening until at least 90 days after the last dose of vorasidenib; be surgically sterile at least 6 months prior to the first dose of investigational medicinal product (IMP) in the study; or be postmenopausal. Female participants of childbearing potential must have a negative serum pregnancy test at Screening and prior to the first dose of IMP in the study.
Male participants with female partners of childbearing potential must be sterile, be willing to use 2 effective methods of birth control from Screening until at least 90 days after the last dose of vorasidenib, or practice abstinence from Screening until at least 90 days after the last dose of vorasidenib. Abstinence is acceptable only as true abstinence when this is in line with the preferred and usual lifestyle of the participant. Male participants should also agree to not donate sperm for the duration of the study and until at least 90 days after the last dose of vorasidenib.
The participant is a continuous nonsmoker who has not used nicotine-containing products (e.g., snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) for at least 3 months prior to the first dose of IMP in the study based on a cotinine test result.
The participant is considered by the investigator (or designee, if applicable) to be in good general health as determined by medical history, full physical examination, clinical laboratory test results, 12-lead electrocardiogram (ECG) results, and vital sign measurements findings at screening and admission.

Exclusion criteria

The participant is a WOCBP who is pregnant, lactating, or planning to become pregnant within at least 90 days after the last dose of vorasidenib in the study; the participant is on oral contraceptive pills or contraceptive patch within 14 days or 5 half-lives (whichever is longer) prior to the first dose of IMP in the study; the participant used a hormonal IUD or vaginal ring within 3 months prior to the first dose of IMP in the study; or the participant received any injectable or implantable hormone-containing product within 1 year prior to the first dose of IMP in the study.
The participant has consumed grapefruit or grapefruit juice or Seville orange or Seville orange-containing products (e.g., marmalade) within 14 days prior to the first dose of IMP in the study.
The participant has ingested vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard) and charbroiled meats within 14 days prior to the first dose of IMP in the study.
The participant has consumed caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate), alcohol, or products containing any of these within 48 hours prior to the first dose of IMP in the study.
The participant is unable or unwilling to abstain from recreational drugs, alcohol, caffeine, xanthine-containing beverages or food (e.g., coffee, tea, chocolate, and caffeinated sodas, colas), grapefruit, grapefruit juice, Seville oranges, or products containing any of these, from 48 hours (caffeine, xanthine-containing beverages or food, alcohol) or 14 days (recreational drugs, grapefruit, grapefruit juice, Seville oranges, or Seville orange-containing products) prior to the first dose of IMP in the study until the Discharge/Early Termination visit.
The participant has received any vaccine or used any prescription (including hormonal birth control or hormone replacement therapy) or over-the-counter medications (except acetaminophen/paracetamol [up to 2 g per 24 hours] or ibuprofen [up to 1.2 g per 24 hours]), including herbal (e.g., St. John's Wort) or nutritional supplements, within 14 days or 5 drug half-lives, whichever is longer, prior to the first dose of IMP in the study.

Trial design

Primary purpose

Basic Science

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

28 participants in 1 patient group

Vorasidenib and cytochrome P450 and transporter index substrates

Experimental group

Description:

Participants will receive a single oral dose of 50mg flurbiprofen, 20mg omeprazole, 2mg midazolam and 0.5mg repaglinide on Day 1, 150mg bupropion on Day 2, and 10mg rosuvastatin on Day 5. Participants will receive an oral daily dose of 40mg vorasidenib from Day 8 to Day 28. In addition, participants will receive a single oral dose of 50mg flurbiprofen, 20mg omeprazole, 2mg midazolam and 0.5mg repaglinide on Day 22, 150mg bupropion on Day 23, and 10mg rosuvastatin on Day 26, co-administered with vorasidenib.