Safety and Pharmacokinetic Study of Inhaled Esketamine in Healthy Volunteers

One-centre Safety and Pharmacokinetics Phase I Study of Inhaled Esketamine in Healthy Volunteers With Two Single Ascending Dose and One Double-blind Multiple Ascending Dose Parts

The planned study is to determine the pharmacokinetic properties of Esketamine and safety assessment with inhaled Esketamine after different number of inhalations and different dosing sequences within three parts of the study.

This is to be one-centre, single ascending dose and double-blind placebo controlled multiple dose three part study of Esketamine DPI (dry powder inhaler) in healthy volunteers.

PART A is a single dose, open-label part with Esketamine DPI inhalations administered with dose escalation between cohorts.

PART B is a single dose, open-label part with Esketamine DPI inhalations administered in different dosing sequences with dose escalation between cohorts.

PART C is a multiple dose, double-blind, placebo-controlled part with Esketamine DPI inhalations administered in different cycles of treatment (with four dosing sequences within two weeks) with dose escalation between cohorts. Participants in this part will be randomized to receive Esketamine DPI or placebo in 3:1 ratio.

Pharmacokinetic properties and safety of Esketamine DPI will be determined following different number of inhalations in PART A, different dosing sequences in PART B and different cycles of treatment in PART C.

Inclusion Criteria:

• Caucasian female or male,
• Age: 18-55 years old, inclusive,
• Body-mass index (BMI): ≥18.5 kg/m^2 and <29.9 kg/m^2
• Non-smoker and nonuser of tobacco products for at least 1 year before screening,
• Physical examination without any clinically relevant abnormality,
• Laboratory values not clinically significant,
• Volunteer (or his/her partner) of childbearing potential willingness to use acceptable forms of contraception.

Exclusion Criteria:

• Known allergy or hypersensitivity to ketamine or its derivates and/or to any study product excipients,
• Any known significant current or past acute or chronic disease or condition,
• Participation in other clinical trial within 90 days preceding the screening,
• Blood drawn within 30 days prior to inclusion to the study (more or equal to 300mL),
• Positive results from pregnancy test for female participants,
• Lactation in women participants,
• Hypotension or hypertension in medical history,
• Narcotic, alcohol addiction or abuse,
• Participant who adhere to a special diet (e.g. low calories, vegetarian).