Clinical trial NCT06726382: KF2024#1-trial: Esketamine Interaction Study
Official title: KF2024#1-trial: Esketamine Interaction Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Drug Interactions
Food-drug Interaction
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: University of Helsinki
First posted: 2024-12-10
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Area under the plasma concentration - time curve of esketamine
timeFrame: 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 outcomes:
measure: Peak plasma concentration for both esketamine and its metabolites
timeFrame: 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.
measure: Half-life for both esketamine and its metabolites
timeFrame: 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.
measure: Time to peak plasma concentration for both esketamine and its metabolites
timeFrame: 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.
measure: Fractional areas under concentration-time curve (AUC) for both esketamine and its metabolites
timeFrame: 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.
measure: Areas under concentration-time curve (AUC) for esketamine metabolites
timeFrame: 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.
measure: Blood pressure
timeFrame: 0, 60, 120 and 240 min after administration
measure: Heart rate
timeFrame: 0, 60, 120 and 240 min after administration
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Department of Clinical Pharmacology
Study officials:
affiliation: Helsinki University Central Hospital
name: Janne T Backman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: