KF2024#1-trial: Esketamine Interaction Study

NCT06726382 | Completed Phase 1

• 2 other identifiers: KF2024#12024-516892-34-00
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Interactions; Food-drug Interaction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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.

Study Arms (4)

Esketamine Nasal Spray

ACTIVE COMPARATOR

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

Esketamine p.o. and water

EXPERIMENTAL

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

Esketamine p.o. and grapefruit juice

EXPERIMENTAL

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; Other: Grapefruit juice

Esketamine p.o. and Cobisistat

EXPERIMENTAL

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; Drug: Cobicistat 150 MG

Interventions

Esketamine Nasal Spray DRUG

1 x 28 mg dose

Also known as: Esketamine, Spravato, Janssen-Cilag International NV

Esketamine Nasal Spray

Esketamine 28 mg DRUG

1 x 5,6 ml p.o.

Also known as: Esketamine Kalceks 5 mg/ml, AS KALCEKS

Esketamine p.o. and Cobisistat; Esketamine p.o. and grapefruit juice; Esketamine p.o. and water

Cobicistat 150 MG DRUG

1 x 150 mg tablet

Also known as: Tybost 150 mg tablet, GILEAD

Esketamine p.o. and Cobisistat

Grapefruit juice OTHER

250 ml grapefruit juice at 8.00 and 9.00 a.m. on the study day.

Esketamine p.o. and grapefruit juice

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Helsinki University Central Hospital: lead
• University of Helsinki: collaborator

Study Sites (1)

Department of Clinical Pharmacology

Helsinki, Finland

Location

MeSH Terms

Interventions

Esketamine; Cobicistat; Tablets

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Janne T Backman, MD, PhD

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 3, 2024
• First Posted: December 10, 2024
• Study Start: December 9, 2024
• Primary Completion: April 29, 2025
• Study Completion: April 29, 2025
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)