KF2024#1-trial: Esketamine Interaction Study

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.

Study Overview

• Status: Completed
• Conditions: Food-drug Interaction; Drug Interactions
• Intervention / Treatment: Drug: Esketamine Nasal Spray; Drug: Esketamine 28 mg; Drug: Cobicistat 150 MG; Other: Grapefruit juice

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Department of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Esketamine Nasal Spray; 1 x 28 mg dose; Other Names: Esketamine, Spravato, Janssen-Cilag International NV
Experimental: Esketamine p.o. and water; 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.	Drug: Esketamine 28 mg; 1 x 5,6 ml p.o.; Other Names: Esketamine Kalceks 5 mg/ml, AS KALCEKS
Experimental: Esketamine p.o. and grapefruit juice; 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.	Drug: Esketamine 28 mg; 1 x 5,6 ml p.o.; Other Names: Esketamine Kalceks 5 mg/ml, AS KALCEKS; Other: Grapefruit juice; 250 ml grapefruit juice at 8.00 and 9.00 a.m. on the study day.
Experimental: Esketamine p.o. and Cobisistat; 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.	Drug: Esketamine 28 mg; 1 x 5,6 ml p.o.; Other Names: Esketamine Kalceks 5 mg/ml, AS KALCEKS; Drug: Cobicistat 150 MG; 1 x 150 mg tablet; Other Names: Tybost 150 mg tablet, GILEAD

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration for both esketamine and its metabolites		Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 minutes 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 minutes 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 minutes 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 minutes 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 minutes and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.
Blood pressure	Blood pressure (safety parameter)	0, 60, 120 and 240 minutes after administration
Heart rate	Heart rate (Safety parameter)	0, 60, 120 and 240 minutes after administration

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: University of Helsinki
• Investigators: Principal Investigator: Janne T Backman, MD, PhD, Helsinki University Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Actual): April 29, 2025
• Study Completion (Actual): April 29, 2025

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: December 9, 2024
• First Posted (Actual): December 10, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Dosage Forms; Thiazoles; Azoles; Acids, Acyclic; Carboxylic Acids; Carbamates; Cobicistat; Esketamine; Tablets
• Other Study ID Numbers: KF2024#1; 2024-516892-34-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No