Safety and Pharmacokinetic Study of Inhaled Esketamine in Healthy Volunteers

Celon Pharma SA63 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Healthy Volunteers

Interventions

Esketamine DPIDRUG

Participants will receive different number of consecutive Esketamine DPI inhalations, consider as a single dose. There will be dose escalation between cohorts.

Esketamine DPIDRUG

Participants will receive different dosing sequences of Esketamine DPI inhalations, consider as a single dose. There will be dose escalation between cohorts. Number of Esketamine DPI inhalations within a dosing sequence will be defined based on results from PART A of the study. Dose: very low, low, medium, high.

Esketamine DPIDRUG

Participants will receive different cycle of treatment consisting of 4 dosing sequences administered within 2 weeks. There will be dose escalation between cohorts. Participants in this part will be randomized to receive Esketamine DPI or placebo in 3:1 ratio. Number of Esketamine DPI inhalations within a dosing sequence will be defined based on results from PART A and PART B of the study. Dose: very low, low, medium, high.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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).

Locations (1)

BioResearch Group Sp. z o.o.

Kajetany, Poland

Outcomes

Primary Outcomes

Cmax - maximum Esketamine plasma concentration

The maximum concentration of the Esketamine in plasma after drug administration, obtained directly from the measured concentrations.

Time frame: up to 24 hours after each study drug administration in PART A, B and C of the study.

AUC (0-24) - area under the Esketamine plasma concentration-time curve from time 0 to 24 hours after study drug administration

The AUC(0-24) is a measure of total plasma exposure to the drug from time point zero to 24 hours after study drug administration.

Time frame: up to 24 hours after each study drug administration in PART A, B and C of the study.

Number of inhalations needed to achieve the assumed Esketamine antidepressive plasma concentration.

Time frame: up to 24 hours after study drug administration in PART A

Number of inhalations within dosing sequence needed to maintain the assumed Esketamine antidepressive plasma concentration.

Time frame: up to 24 hours after study drug administration in PART B

Secondary Outcomes

AUC (0-inf) - area under the Esketamine plasma concentration-time curve from time 0 to infinity time

The AUC(0-inf) is a measure of total plasma exposure to the drug from time point zero extrapolated to infinity.

Time frame: up to 24 hours after each study drug administration in PART A, B and C of the study.

Tmax - time to reach maximum Esketamine plasma concentration

The Tmax is time to reach the maximum plasma concentration (Cmax), obtained directly from the actual sampling times.

Time frame: up to 24 hours after each study drug administration in PART A, B and C of the study.

Data from ClinicalTrials.gov

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