Drug Interactions, Food-drug Interaction
Conditions
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.
Interventions
1 x 28 mg dose
DRUGEsketamine 28 mg
1 x 5,6 ml p.o.
1 x 150 mg tablet
OTHERGrapefruit juice
250 ml grapefruit juice at 8.00 and 9.00 a.m. on the study day.
Sponsors
Helsinki University Central Hospital
University of Helsinki
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 0, 60, 120 and 240 minutes after administration | Blood pressure (safety parameter) |
| Heart rate | 0, 60, 120 and 240 minutes after administration | Heart rate (Safety parameter) |
Countries
Finland
Contacts
PRINCIPAL_INVESTIGATORJanne T Backman, MD, PhD
Helsinki University Central Hospital
Outcome results
None listed