A Study to Evaluate the Effect of Carbamazepine or Itraconazole on Radiprodil in Healthy Adult Participants

NCT07884734 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RAD-GRIN-508
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label, 2-part study in healthy adult participants to evaluate the pharmacokinetics and safety of radiprodil when coadministered with either the CYP3A4 inducer carbamazepine or the CYP3A4 inhibitor itraconazole. Up to 36 participants will be enrolled, with approximately 18 participants in Part A and 18 participants in Part B.

Conditions

Healthy Adult Participants

Keywords

Radiprodil; Carbamazepine; Itraconazole

Outcome Measures

Primary Outcomes (6)

• AUClast of Radiprodil - Part A

  Area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast) of radiprodil following administration of radiprodil alone on Day 1 and with carbamazepine on Day 16. The effect of carbamazepine will be assessed using the geometric mean ratio and 90% confidence interval.

  Part A: Day 1 through Day 19

• AUCinf of Radiprodil - Part A

  Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUCinf) of radiprodil following administration of radiprodil alone on Day 1 and with carbamazepine on Day 16. The effect of carbamazepine will be assessed using the geometric mean ratio and 90% confidence interval.

  Part A: Day 1 through Day 19

• Cmax of Radiprodil - Part A

  Maximum observed plasma concentration (Cmax) of radiprodil following administration of radiprodil alone on Day 1 and with carbamazepine on Day 16. The effect of carbamazepine will be assessed using the geometric mean ratio and 90% confidence interval.

  Part A: Day 1 through Day 19

• AUClast of Radiprodil - Part B

  Area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast) of radiprodil following administration of radiprodil alone on Day 1 and with itraconazole on Day 9. The effect of itraconazole will be assessed using the geometric mean ratio and 90% confidence interval.

  Part B: Day 1 through Day 12

• AUCinf of Radiprodil - Part B

  Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUCinf) of radiprodil following administration of radiprodil alone on Day 1 and with itraconazole on Day 9. The effect of itraconazole will be assessed using the geometric mean ratio and 90% confidence interval.

  Part B: Day 1 through Day 12

• Cmax of Radiprodil - Part B

  Maximum observed plasma concentration (Cmax) of radiprodil following administration of radiprodil alone on Day 1 and with itraconazole on Day 9. The effect of itraconazole will be assessed using the geometric mean ratio and 90% confidence interval.

  Part B: Day 1 through Day 12

Secondary Outcomes (28)

• AUClast of Carbamazepine - Part A

  Part A: Day 16 (up to 12 hours post-dose)

• AUCtau of Carbamazepine - Part A

  Part A: Day 16 (up to 12 hours post-dose)

• Cmax of Carbamazepine - Part A

  Part A: Day 16 (up to 12 hours post-dose)

• Tmax of Carbamazepine - Part A

  Part A: Day 16 (up to 12 hours post-dose)

• AUClast of Itraconazole - Part B

  Part B: Day 9 through Day 10 (up to 24 hours post-dose)

Study Arms (2)

Part A: Radiprodil With Carbamazepine

EXPERIMENTAL

Participants will receive a single oral dose of radiprodil 30 mg under fed conditions on Day 1. Carbamazepine will then be administered orally twice daily with food at escalating doses: 100 mg BID on Days 4 to 5, 200 mg BID on Days 6 to 7, and 300 mg BID on Days 8 to 15. On Day 16, radiprodil 30 mg will be coadministered with carbamazepine 300 mg under fed conditions. Carbamazepine 300 mg BID will continue on Days 17 to 18. Participants will be discharged on Day 21 and attend a follow-up visit 30 days ± 2 days after the last carbamazepine dose.

Drug: Radiprodil; Drug: Carbamazepine

Part B: Radiprodil With Itraconazole

EXPERIMENTAL

Participants will receive a single oral dose of radiprodil 15 mg under fed conditions on Day 1. Itraconazole 200 mg once daily will be administered orally with food on Days 4 to 8. On Day 9, radiprodil 15 mg will be coadministered with itraconazole 200 mg under fed conditions. Itraconazole 200 mg once daily will continue on Days 10 to 11. Participants will be discharged on Day 12 and attend a follow-up visit 30 days ± 2 days after the last itraconazole dose.

Drug: Radiprodil; Drug: Itraconazole (200 mg)

Interventions

Radiprodil DRUG

Radiprodil administered orally as a single dose of 30 mg in Part A or 15 mg in Part B under fed conditions.

Also known as: RGH-896, Radiprodil oral suspension

Part A: Radiprodil With Carbamazepine; Part B: Radiprodil With Itraconazole

Carbamazepine DRUG

Carbamazepine administered orally twice daily at doses of 100 mg, 200 mg, and 300 mg in Part A to evaluate the effect of CYP3A4 induction on the pharmacokinetics of radiprodil.

Part A: Radiprodil With Carbamazepine

Itraconazole (200 mg) DRUG

Itraconazole administered orally at 200 mg once daily in Part B to evaluate the effect of CYP3A4 inhibition on the pharmacokinetics of radiprodil.

Part B: Radiprodil With Itraconazole

Eligibility Criteria

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

You may qualify if:

• Healthy male and female adults aged 18 to 55 years inclusive at Screening.
• Body mass index between 18 and 32 kg/m² inclusive and weight of at least 50 kg at Screening.
• Healthy in the opinion of the Principal Investigator, based on medical history, physical examination, 12-lead ECG, vital signs, and clinical laboratory assessments.
• Female participants must be non-lactating and either of non-childbearing potential, postmenopausal, or, if of childbearing potential, must have negative pregnancy tests and agree to required contraception and ova donation restrictions.
• Male participants must agree to sperm donation restrictions and required contraception measures.
• For Part A only, participants must not be of Asian descent due to increased risk associated with carbamazepine exposure.
• Able to provide signed informed consent and comply with study requirements, including dietary restrictions and confinement at the clinical research unit.

You may not qualify if:

• History of contraindication or hypersensitivity to radiprodil, carbamazepine, itraconazole, or formulation components.
• For Part A only, HLA genotypes associated with increased risk of carbamazepine-induced severe cutaneous adverse reactions.
• Any medical condition that, in the opinion of the Principal Investigator, would pose additional risk or interfere with drug absorption, distribution, metabolism, or excretion.
• Pregnancy, breastfeeding, or positive pregnancy test.
• Significant neuropsychiatric, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, urologic, neurological, malignancy, psychiatric disease, brain surgery, or brain injury.
• Clinically significant allergic conditions.
• History of illicit drug abuse or alcohol abuse within 2 years of Screening.
• History of suicide attempt, deliberate self-harm, significant suicidal ideation, or suicidal behaviour on C-SSRS.
• Excessive alcohol or caffeine consumption.
• Positive drug, alcohol, cotinine, or relevant substance screen at Screening or Day -1.
• Recent marijuana, tobacco, nicotine, prescription drug, investigational product, OTC medication, herbal product, vaccine, blood donation, acute illness, relevant surgery, or blood transfusion as defined in the protocol.
• Positive serology for HBsAg, HCV antibody, or HIV antibody.
• Abnormal blood pressure, pulse rate, clinically significant ECG abnormality, QTcF \>450 msec, or history of prolonged QT syndrome.
• Restricted food or drink consumption before dosing, including alcohol, grapefruit/pomelo/star fruit/Seville orange products, poppy seeds, and xanthine-containing products.
• Poor venous access.

Sponsors & Collaborators

• GRIN Therapeutics, Inc.: lead
• Parexel: collaborator

Study Sites (1)

California Clinical Trials Medical Group (CCTMG)

Glendale, California, 91206, United States

Location

MeSH Terms

Interventions

radiprodil; Carbamazepine; Itraconazole

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Piperazines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2026
• First Posted: October 21, 2026
• Study Start: June 8, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)