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

NCT07235748 | Completed Phase 1 FDA Drug

• 1 other identifier: S095032-230
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Adult Participants

Outcome Measures

Primary Outcomes (8)

• Maximum concentration (Cmax) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin

  Through Day 29

• Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUC0-last) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin

  Through Day 29

• Area under the plasma concentration versus time curve from 0 extrapolated to infinity (AUC0-inf) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin

  Through Day 29

• Time corresponding to Cmax (Tmax) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin

  Through Day 29

• Terminal half-life (t1/2) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin

  Through Day 29

• Apparent oral clearance (CL/F) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin

  Through Day 29

• Apparent volume of distribution during the terminal phase following oral administration (Vz/F) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin

  Through Day 29

• Elimination rate constant (Kel) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin

  Through Day 29

Secondary Outcomes (2)

• Number of Adverse Events (AEs)

  Through the Follow-up Phone Call (Day 57)

• Trough plasma concentration (Ctrough) of vorasidenib

  Through Day 29

Study Arms (1)

Vorasidenib and cytochrome P450 and transporter index substrates

EXPERIMENTAL

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.

Drug: Vorasidenib; Drug: Bupropion; Drug: Flurbiprofen; Drug: Omeprazole; Drug: Midazolam; Drug: Repaglinide; Drug: Rosuvastatin

Interventions

Omeprazole DRUG

20mg taken orally on Day 1 and Day 22

Vorasidenib and cytochrome P450 and transporter index substrates

Repaglinide DRUG

0.5mg taken orally on Day 1 and Day 22

Vorasidenib and cytochrome P450 and transporter index substrates

Rosuvastatin DRUG

10mg taken orally on Day 5 and Day 26

Vorasidenib and cytochrome P450 and transporter index substrates

Vorasidenib DRUG

40mg taken orally daily from Day 8 through Day 28

Vorasidenib and cytochrome P450 and transporter index substrates

Bupropion DRUG

150mg taken orally on Day 2 and Day 23

Vorasidenib and cytochrome P450 and transporter index substrates

Flurbiprofen DRUG

50mg taken orally on Day 1 and Day 22

Vorasidenib and cytochrome P450 and transporter index substrates

Midazolam DRUG

2mg taken orally on Day 1 and Day 22

Vorasidenib and cytochrome P450 and transporter index substrates

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Recherches Internationales Servier (I.R.I.S.): lead

Study Sites (1)

Celerion

Belfast, BT9 6AD, United Kingdom

Location

MeSH Terms

Interventions

vorasidenib; Bupropion; Flurbiprofen; Omeprazole; Midazolam; repaglinide; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals; Propionates; Acids, Acyclic; Carboxylic Acids; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Pyrimidines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 19, 2025
• Study Start: October 7, 2025
• Primary Completion: December 23, 2025
• Study Completion: December 23, 2025
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorization in EEA or US if the study is used for the approval.
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Locations

GB (1)