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KF2024#1-trial: Esketamine Interaction Study

This open-label, Phase I trial (n=12) will investigate the effects of different methods of esketamine administration (28 mg nasal spray vs. 28 mg oral solution) with and without CYP3A4 inhibitors (grapefruit juice or cobicistat) on drug absorption and metabolism.

Target Enrollment
12 participants
Study Type
Phase I interventional
Design
Randomized

Detailed Description

Open, randomized four-period crossover in 12 healthy volunteers comparing intranasal Esketamine (Spravato 28 mg) and oral esketamine 28 mg with water, grapefruit juice, or cobicistat to assess effects on plasma concentrations.

Primary outcome is area under the plasma concentration–time curve (AUC) of esketamine; PK sampling to 24 hours postdose with safety and tolerability monitoring.

Study Protocol

Preparation

sessions

Dosing

4 sessions
1440 min each

Integration

sessions

Study Arms & Interventions

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.

Interventions

  • Esketamine28 mg
    via Other• single dose• 1 doses total

    Spravato 28 mg intranasal

Oral + 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.

Interventions

  • Esketamine28 mg
    via Oral• single dose• 1 doses total

    Esketamine Kalceks 5 mg/ml, 5.6 ml oral

Oral + grapefruit

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.

Interventions

  • Esketamine28 mg
    via Oral• single dose• 1 doses total

    Esketamine 28 mg with grapefruit juice

Oral + cobicistat

experimental

150 mg Cobicistat 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.

Interventions

  • Esketamine28 mg
    via Oral• single dose• 1 doses total

    Esketamine 28 mg oral

  • Placebo
    via Oral• single dose

    Cobicistat 150 mg tablet (Tybost) given at 8:00

Participants

Ages
18 – 45
Sexes
Male & Female

Inclusion 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

  • 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 Details

Locations

Department of Clinical Pharmacology — Helsinki, Finland

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