Safety and Pharmacokinetic Study of Inhaled Esketamine in Healthy Volunteers

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03407872
• Other study ID #: 01KET2017
• Status: Completed
• Phase: Phase 1
• Start date: December 9, 2017
• Est. completion date: June 19, 2018

Study information

• Verified date: July 2018
• Source: Celon Pharma SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: June 19, 2018
• Est. primary completion date: May 20, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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

Locations

Country	Name	City	State
Poland	BioResearch Group Sp. z o.o.	Kajetany

Sponsors (2)

Lead Sponsor	Collaborator
Celon Pharma SA	The National Centre for Research and Development, Poland

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax - maximum Esketamine plasma concentration	The maximum concentration of the Esketamine in plasma after drug administration, obtained directly from the measured concentrations.	up to 24 hours after each study drug administration in PART A, B and C of the study.
Primary	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.	up to 24 hours after each study drug administration in PART A, B and C of the study.
Primary	Number of inhalations needed to achieve the assumed Esketamine antidepressive plasma concentration.		up to 24 hours after study drug administration in PART A
Primary	Number of inhalations within dosing sequence needed to maintain the assumed Esketamine antidepressive plasma concentration.		up to 24 hours after study drug administration in PART B
Secondary	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.	up to 24 hours after each study drug administration in PART A, B and C of the study.
Secondary	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.	up to 24 hours after each study drug administration in PART A, B and C of the study.
Secondary	Kel -elimination rate constant	Kel will be estimated via linear regression of time versus log of concentration.	up to 24 hours after each study drug administration in PART A, B and C of the study.
Secondary	T1/2 - plasma elimination half-life for Esketamine	T1/2 will be calculated as 0.693/Kel.	up to 24 hours after each study drug administration in PART A, B and C of the study.
Secondary	Cmax - maximum Esnorketamine plasma concentration	The maximum concentration of the Esnorketamine in plasma after drug administration, obtained directly from the measured concentrations. Esnorketamine is Esketamine's main metabolite.	up to 24 hours after each study drug administration in PART A, B and C of the study.
Secondary	AUC (0-24) - area under the Esnorketamine plasma concentration-time curve from time 0 to 24 hours after study drug administration.	The AUC(0-24) is a measure of total Esnorketamine plasma exposure to the metabolite from time point zero to 24 hours after study drug administration. Esnorketamine is Esketamine's main metabolite.	up to 24 hours after each study drug administration in PART A, B and C of the study.
Secondary	Tmax - time to reach maximum Esnorketamine plasma concentration.	The Tmax is time to reach the maximum Esnorketamine plasma concentration (Cmax), obtained directly from the actual sampling times. Esnorketamine is Esketamine's main metabolite.	up to 24 hours after each study drug administration in PART A, B and C of the study.
Secondary	Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs).	Participants during hospitalization will be closely observed to assure maximal safety and to collect occurrence of all adverse event. To follow-up on all study participants telephone calls with a request for information regarding their health condition will be made. All adverse events will be collected with special attention to occurrence of psychotomimetic and dissociative effects after study drug administration.	up to 7 days in PART A and PART B of the study and up to 25 days in PART C of the study.