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.
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.
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.
Spravato 28 mg intranasal
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.
Esketamine Kalceks 5 mg/ml, 5.6 ml oral
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.
Esketamine 28 mg with grapefruit juice
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.
Esketamine 28 mg oral
Cobicistat 150 mg tablet (Tybost) given at 8:00