KF2024#1-trial: Esketamine Interaction Study

Helsinki University Central Hospital (HUCH)

Status and phase: Not yet enrolling; Phase 1

Conditions: Drug Interactions; Food-drug Interaction

Treatments: Drug: Esketamine Nasal Spray; Drug: Cobicistat 150 MG; Drug: Esketamine 28 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT06726382

KF2024#1

2024-516892-34-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

Esketamine is a drug which is used for depression treatment, to relieve pain and, in larger doses, in anesthesia. Spravato nasal spray is the only esketamine product on the market used for the treatment of depression, but the high price limits the use of the drug.

The aim of this study is to compare the concentration of esketamine after nasal (licensed product Spravato) and oral administration with and without a CYP3A4 inhibitor. Grapefruit juice and cobicistat are studied as CYP3A4 inhibitors in the study.

In an open four-phase, randomized, alternating study with 12 healthy volunteers, the subjects will receive Spravato 28 mg nasal or esketamine 28 mg oral with either grapefruit juice, cobicistat or water in the study facilities. Blood samples will be collected and esketamine pharmacokinetics will be monitored up to 24 hours postdose. Primary endpoint is area under the plasma concentration-time curve of esketamine.

Enrollment: 12 estimated patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• signed consent
• age 18-45 years
• healthy
• no indications of substance abuse
• Accepted results from laboratory tests (blood hemoglobin, basic blood count and blood platelets, alanine aminotransferase, alkaline phosphatase, glutamyl transferase, creatinine, plasma potassium and sodium). Negative pregnancy test result (serum human chorionic gonadotropin) for women.
• no significant abnormalities in the ECG
• systolic blood pressure 140 mmHg-100 mmHg
• heart rate ≥50/minute

Exclusion criteria

• significant illness
• less than 3 months since the last clinical trial
• less than 3 months after donating blood
• significant overweight/poor veins
• BMI below 18.5 kg/m2
• past or present mood disorder or suicidality
• substance abuse
• systolic blood pressure below 100 mmHg or above 140 mmHg
• heart rate <50/minute
• conduction disorder or other significant abnormality in the ECG
• smoking
• regular medication (including e-pills and other preparations containing estrogens)
• pregnancy or its planning or breastfeeding
• hypersensitivity to investigational drugs or excipients of medicinal products
• use of natural products (such as St. John's wort)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

12 participants in 4 patient groups

Esketamine Nasal Spray

Active Comparator group

Description:

250 ml water at 8.00 and 9.00 a.m. on the study day. Study drug dose (Esketamine Spravato, 28 mg) nasally at 9.00 a.m. on the study day.

Treatment:

Drug: Esketamine Nasal Spray

Esketamine p.o. and water

Experimental group

Description:

250 ml water at 8.00 and 9.00 a.m. on the study day. Study drug dose (Esketamine Kalceks 5 mg/ml, 28 mg) p.o. at 9.00 a.m. on the study day.

Treatment:

Drug: Esketamine 28 mg

Esketamine p.o. and grapefruit juice

Experimental group

Description:

250 ml grapefruit juice at 8.00 and 9.00 a.m. on the study day. Study drug dose (Esketamine Kalceks 5 mg/ml, 28 mg) p.o. at 9.00 a.m. on the study day.

Treatment:

Drug: Esketamine 28 mg

Esketamine p.o. and Cobisistat

Experimental group

Description:

150 mg Cobisistat and 250 ml water at 8.00 a.m. on the study day. Study drug dose (Esketamine Kalceks 5 mg/ml, 28 mg) p.o. and 250 ml water at 9.00 a.m. on the study day.

Treatment:

Drug: Esketamine 28 mg

Drug: Cobicistat 150 MG