KF2024#1-trial: Esketamine Interaction Study

Phase 1

Not yet recruiting

• Conditions: Drug Interactions; Food-drug Interaction
• Interventions: Drug: Esketamine 28 mg; Drug: Esketamine Nasal Spray; Drug: Cobicistat 150 MG

• Registration Number: NCT06726382
• Lead Sponsor: Helsinki University Central Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-12-03
• Study Start: 2024-12-09
• Study First Submitted QC: 2024-12-09
• Last Update Submitted: 2024-12-09
• Study First Posted: 2024-12-10
• Last Update Posted: 2024-12-10
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Esketamine p.o. and water	Esketamine 28 mg	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.
Esketamine p.o. and grapefruit juice	Esketamine 28 mg	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.
Esketamine p.o. and Cobisistat	Cobicistat 150 MG	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.
Esketamine Nasal Spray	Esketamine Nasal Spray	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.
Esketamine p.o. and Cobisistat	Esketamine 28 mg	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.

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration - time curve of esketamine	Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 min and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.

Secondary Outcome Measures

Name	Time	Method
Peak plasma concentration for both esketamine and its metabolites	Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 min and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.
Half-life for both esketamine and its metabolites	Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 min and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.
Time to peak plasma concentration for both esketamine and its metabolites	Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 min and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.
Fractional areas under concentration-time curve (AUC) for both esketamine and its metabolites	Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 min and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.
Areas under concentration-time curve (AUC) for esketamine metabolites	Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 min and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.
Blood pressure	0, 60, 120 and 240 min after administration	Blood pressure (safety parameter)
Heart rate	0, 60, 120 and 240 min after administration	Heart rate (Safety parameter)

Trial Locations

Locations (1)

Department of Clinical Pharmacology; 🇫🇮 Helsinki, Finland