A Study to Evaluate the Pharmacokinetics of Intranasal Esketamine Administered With and Without a Nasal Guide on the Intranasal Device

NCT02060929 | Completed Phase 1

• 2 other identifiers: CR102971ESKETINTRD1004
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Healthy; Esketamine; Intranasal; Nasal Guide; Pharmacokinetics

Outcome Measures

Primary Outcomes (11)

• Maximum Observed Plasma Concentration (Cmax) of Esketamine

  Cmax is defined as maximum observed analyte concentration.

  Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Esketamine

  Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

  Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours

• Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUClast) of Esketamine

  The AUClast is area under the plasma concentration-time curve from time zero to the last quantifiable concentration.

  Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Esketamine

  The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of Area under Curve (AUC) last and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration

  Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours

• Elimination Half-Life Period (T1/2) of Esketamine

  T1/2 is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal rate-constant (lambda\[z\]) of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).

  Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours

• First-order Rate Constant of Esketamine

  First-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.

  Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours

• Relative Bioavailability (Frel) of Esketamine

  Relative bioavailability is the percentage of the administered dose that is systemically available.

  Pre-dose, and post-dose 7, 12, 22, 32, 40, 50 minutes, 1, 1.25, 1.5, 2, 3, 4, 24 hours

• Change From Baseline in Clinician-Administered Dissociative States Scale (CADSS) Score

  The CADSS is a clinician administered rating scale designed to measure dissociative symptoms. The CADSS comprises 23 subjective items, divided into 3 components: depersonalization, derealization and amnesia. Participant's responses are coded on a 5-point scale (0 = "Not at all" through to 4 = "Extremely). Higher scores indicate worsening.

  Baseline (Day -1) and Day 2

• Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Score

  The BPRS is used for the measurement of psychiatric symptoms. The BPRS is an 18 item questionnaire and each question is rated on a 7-point scale ranging from 1 (not present) to 7 (extremely severe). The total score for the 18 question will be calculated by adding score of each question. The interpretation of the total scores are: 0-9 will indicate "not a schizoaffective case"; 10-20 will indicate "possible schizoaffective case"; and 21 or more, will indicate "evident schizoaffective case". Higher scores indicate worsening.

  Baseline (Day -1) and Day 2

• Change From Baseline in Modified Observers Assessment of Alertness/Sedation (MOAA/S) Score

  The MOAA/S is a 6-point ordinal scale measuring a patient's level of sedation. Scores range from 0 (No response to painful stimulus \[trapezius squeeze\]) to 5 (Responds readily to name spoken in normal tone \[awake\]). MOAA/S scores were classified as 0-1, 2-4 and 5.

  Baseline (Day 1) and Day 2

• Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score

  The C-SSRS is a clinical interview to assess severity and track suicidal events providing a summary of both suicidal ideation and behavior to identify the level and type of suicidality present.

  Baseline (Screening - Day -21 to Day -2) and follow-up visit (11 to 13 days after final dose)

Study Arms (2)

Sequence 1

EXPERIMENTAL

Participants will self administer 1 spray of esketamine solution to each nostril using a intranasal (through nose) device with a nasal guide on Day 1 of period 1 as treatment regimen A at time 0 and repeated twice every 5 minutes (total dose: 84 mg). There will be a washout period of 5-10 days between the treatment regimens. On Day 1 of period 2, participants will self administer 1 spray of esketamine solution to each nostril using a intranasal device without a nasal guide as treatment regimen B at time 0 and repeated twice every 5 minutes (total dose: 84 mg).

Drug: Esketamine

Sequence 2

EXPERIMENTAL

Participants will self administer 1 spray of esketamine solution to each nostril using a intranasal device without a nasal guide on Day 1 of period 1 as treatment regimen B at time 0 and repeated twice every 5 minutes (total dose: 84 mg). There will be a washout period of 5-10 days between the treatment regimens. On Day 1 of period 2, participants will self administer 1 spray of esketamine solution to each nostril using a intranasal device with a nasal guide as treatment regimen A at time 0 and repeated twice every 5 minutes (total dose: 84 mg).

Drug: Esketamine

Interventions

Esketamine DRUG

Participants will self administer 1 spray of esketamine solution using a intranasal device with a nasal guide in Treatment A regimen and without nasal guide inTreatment B regimen at time 0 and repeated twice every 5 minutes (total dose: 84 mg).

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Merksem, Belgium

Location

MeSH Terms

Interventions

Esketamine

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2014
• First Posted: February 12, 2014
• Study Start: October 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: March 13, 2014

Record last verified: 2014-03

Locations

BE (1)