Clinical trial NCT02060929: A Study to Evaluate the Pharmacokinetics of Intranasal Esketamine Administered With and Without a Nasal Guide on the Intranasal Device
Official title: An Open-Label Phase 1 Study to Evaluate the Pharmacokinetics of Intranasal Esketamine Administered With and Without a Nasal Guide on the Intranasal Device
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Esketamine
Intranasal
Nasal Guide
Pharmacokinetics
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-02-12
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to evaluate the pharmacokinetics (what the body does to the medication) of intranasally (through the nose) administered esketamine using a device with and without a nasal guide in healthy participants.

Detailed description: This is a randomized (the study medication is assigned by chance), single-center, single-dose, 2-way crossover (participants may receive different interventions sequentially during the study in 2 sequence groups), open-label (all people know the identity of the intervention) study. Approximately, 14 participants will be enrolled in this study. This study will consist of a screening phase of up to 21 days, a treatment phase of 3 days, and a follow-up phase of 9-13 days. Participants will be randomly allocated to 1 of the 2 treatment groups (Sequence 1 and 2). In sequence 1, participants will self-administer esketamine intranasally using a device with nasal guide as treatment A on Day 1 of period 1 and intranasally esketamine using a device without nasal guide as treatment B on Day 1 of period 2. In sequence 2, participants will self-administer intranasally esketamine as treatment B on Day 1 of period 1 and intranasally esketamine as treatment A on Day 1 of period 2. There will be a washout period of 5 to 10 days between each treatment regimen. Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, vital signs, physical examination, pulse oximetry, targeted nasal examination, nasal device questionnaire, and in addition to these evaluations, specific scales will be used to assess the safety. The study duration for each participant will be approximately 45 days.

Eligibility criteria: Inclusion Criteria:

* Agrees to protocol-defined use of effective contraception
* If a woman, must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at screening; and a negative urine pregnancy test on Day -1 of each treatment period
* Body mass index (BMI) (weight \[kg\]/height2 \[m\]2) between 18 and 30 kg/m2 (inclusive), and body weight not less than 50 kg
* Blood pressure (after the participant is supine for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic
* A 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function

Exclusion Criteria:

* Current or prior history of psychiatric disorder including but not limited to psychotic, bipolar, major depressive, or anxiety disorder
* Clinically significant medical illness including cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders , lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic disease, infection, hypertension or vascular disorders, kidney or urinary tract disturbances, sleep apnea, myasthenia gravis, or any other illness
* Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at admission to the study center (Day -1) as deemed appropriate by the investigator
* Clinically significant abnormal physical examination, vital signs, or 12-lead ECG at screening or at admission to the study center (Day -1 of each treatment period) as deemed appropriate by the investigator
* Has an abnormal or deviated nasal septum with any 1 or more of the following symptoms: blockage of 1 or both nostrils, nasal congestion (especially 1-sided), frequent nosebleeds, frequent sinus infections, noisy breathing during sleep, facial pain, headaches, and postnasal drip

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Esketamine
timeFrame: Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Esketamine
timeFrame: Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUClast) of Esketamine
timeFrame: Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Esketamine
timeFrame: Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours
measure: Elimination Half-Life Period (T1/2) of Esketamine
timeFrame: Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours
measure: First-order Rate Constant of Esketamine
timeFrame: Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours
measure: Relative Bioavailability (Frel) of Esketamine
timeFrame: Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours
measure: Change From Baseline in Clinician-Administered Dissociative States Scale (CADSS) Score
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Score
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline in Modified Observers Assessment of Alertness/Sedation (MOAA/S) Score
timeFrame: Baseline (Day 1) and Day 2
measure: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Baseline (Screening - Day -21 to Day -2) and follow-up visit (11 to 13 days after final dose)
Secondary outcomes:
Other outcomes:
Locations:
city: Merksem
country: Belgium
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: