Safety and Pharmacokinetic Study of Inhaled Esketamine in Healthy Volunteers

NCT ID: NCT03407872

Last Updated: 2018-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-09
• Study Completion Date: 2018-06-19

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.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

PART A

6 cohorts will receive single dose of Esketamine DPI administered with dose escalation between cohorts.

Group Type: EXPERIMENTAL

Esketamine DPI

Intervention Type: DRUG

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

PART B

4 cohorts will receive single dose of Esketamine DPI administered with dose escalation between cohorts.

Group Type: EXPERIMENTAL

Esketamine DPI

Intervention Type: DRUG

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.

PART C

4 cohorts will receive multiple dose of Esketamine DPI in two weeks' time administered with dose escalation between cohorts.

Group Type: EXPERIMENTAL

Esketamine DPI

Intervention Type: DRUG

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.

PART C placebo

4 cohorts will receive multiple dose of matching placebo in two weeks' time.

Group Type: PLACEBO_COMPARATOR

Placebo DPI

Intervention Type: DRUG

Participants will receive different cycle of treatment consisting of 4 dosing sequences administered within 2 weeks. Participants in this part will be randomized to receive Esketamine DPI or placebo in 3:1 ratio.

In each cohort, number of placebo inhalations within a dosing sequence will correspond to number of Esketamine DPI inhalations.

Interventions

Esketamine DPI

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

Intervention Type: DRUG

Esketamine DPI

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.

Intervention Type: DRUG

Esketamine DPI

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.

Intervention Type: DRUG

Placebo DPI

Participants will receive different cycle of treatment consisting of 4 dosing sequences administered within 2 weeks. Participants in this part will be randomized to receive Esketamine DPI or placebo in 3:1 ratio.

In each cohort, number of placebo inhalations within a dosing sequence will correspond to number of Esketamine DPI inhalations.

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Center for Research and Development, Poland

OTHER

Sponsor Role: collaborator

Celon Pharma SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

BioResearch Group Sp. z o.o.

Kajetany, , Poland

Countries

Poland

Other Identifiers

01KET2017

Identifier Type: -

Identifier Source: org_study_id