Clinical trial NCT03407872: Safety and Pharmacokinetic Study of Inhaled Esketamine in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Celon Pharma SA
Sponsor class: INDUSTRY
Collaborators: name: National Center for Research and Development, Poland
First posted: 2018-01-23
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Cmax - maximum Esketamine plasma concentration
timeFrame: up to 24 hours after each study drug administration in PART A, B and C of the study.
measure: AUC (0-24) - area under the Esketamine plasma concentration-time curve from time 0 to 24 hours after study drug administration
timeFrame: up to 24 hours after each study drug administration in PART A, B and C of the study.
measure: Number of inhalations needed to achieve the assumed Esketamine antidepressive plasma concentration.
timeFrame: up to 24 hours after study drug administration in PART A
measure: Number of inhalations within dosing sequence needed to maintain the assumed Esketamine antidepressive plasma concentration.
timeFrame: up to 24 hours after study drug administration in PART B
Secondary outcomes:
measure: AUC (0-inf) - area under the Esketamine plasma concentration-time curve from time 0 to infinity time
timeFrame: up to 24 hours after each study drug administration in PART A, B and C of the study.
measure: Tmax - time to reach maximum Esketamine plasma concentration
timeFrame: up to 24 hours after each study drug administration in PART A, B and C of the study.
measure: Kel -elimination rate constant
timeFrame: up to 24 hours after each study drug administration in PART A, B and C of the study.
measure: T1/2 - plasma elimination half-life for Esketamine
timeFrame: up to 24 hours after each study drug administration in PART A, B and C of the study.
measure: Cmax - maximum Esnorketamine plasma concentration
timeFrame: up to 24 hours after each study drug administration in PART A, B and C of the study.
measure: AUC (0-24) - area under the Esnorketamine plasma concentration-time curve from time 0 to 24 hours after study drug administration.
timeFrame: up to 24 hours after each study drug administration in PART A, B and C of the study.
measure: Tmax - time to reach maximum Esnorketamine plasma concentration.
timeFrame: up to 24 hours after each study drug administration in PART A, B and C of the study.
measure: Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs).
timeFrame: up to 7 days in PART A and PART B of the study and up to 25 days in PART C of the study.
Other outcomes:
Locations:
city: Kajetany
country: Poland
facility: BioResearch Group Sp. z o.o.
Study officials:
References: