A Pharmacokinetic, Safety and Tolerability Study of Esketamine in Healthy Elderly and Adult Participants

NCT02129088 | Completed Phase 1

• 3 other identifiers: CR103806ESKETINTRD10032013-005372-18
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the pharmacokinetics (explores what the body does to the drug), safety and tolerability of esketamine, administered intranasally (administered through the nose) in healthy elderly (Cohort 1) and healthy adult (Cohort 2) participants.

Conditions

Healthy

Keywords

Healthy; Esketamine; Phase 1; Placebo; Elderly; Adult

Outcome Measures

Primary Outcomes (7)

• Maximum Plasma Concentration (Cmax) of Esketamine

  The Cmax is the maximum plasma concentration.

  0 (pre-dose), 7, 12, 22, 32, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18 and 24 hours after study drug administration

• Time to Reach Maximum Concentration (tmax)

  The tmax is time to reach the maximum observed plasma concentration.

  0 (pre-dose), 7, 12, 22, 32, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18 and 24 hours after study drug administration

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])

  The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.

  0 (pre-dose), 7, 12, 22, 32, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18 and 24 hours after study drug administration

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

  The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

  0 (pre-dose), 7, 12, 22, 32, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18 and 24 hours after study drug administration

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

  Percentage AUC\[0-infinity\] is obtained by extrapolation of the concentration-time curve. It is calculated by AUC\[0-infinity\] minus AUC\[0-last\] divided by AUC\[0-infinity\] multiplied by 100.

  0 (pre-dose), 7, 12, 22, 32, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18 and 24 hours after study drug administration

• Elimination Half-Life (t [1/2] Lambda)

  Elimination half-life (t \[1/2\] Lambda) is associated with the terminal slope (lambda \[z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).

  0 (pre-dose), 7, 12, 22, 32, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18 and 24 hours after study drug administration

• Rate Constant (Lambda[z])

  Lambda(z) is 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 .

  0 (pre-dose), 7, 12, 22, 32, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18 and 24 hour after study drug administration

Study Arms (2)

Cohort 1

EXPERIMENTAL

Participants will receive esketamine 14 milligram (mg) as intranasal spray into each nostril on Day 1.

Drug: Esketamine

Cohort 2

EXPERIMENTAL

All participants will receive esketamine 14 mg as intranasal spray into each nostril on Day 1 of Period 1 as Treatment A and esketamine 14 mg as intranasal spray followed by intranasal administration of placebo solution after 5 and 10 minutes of esketamine administration into each nostril on Day 1 of Period 2 as Treatment B in a fixed sequence.

Drug: Esketamine; Drug: Placebo

Interventions

Esketamine DRUG

Esketamine 14 mg will be self-administered by participants as intranasal spray into each nostril on Day 1 to cohort 1 and cohort 2 in a fixed sequence.

Cohort 1; Cohort 2

Placebo DRUG

Placebo will be self-administered as intranasal spray by participants after 5 and 10 minutes of esketamine administration into each nostril on Day 1 of Treatment period 2 to Cohort 2.

Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female participant must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile, abstinent (abstinence is an acceptable means of birth control only if it is already established as the participant's usual and preferred lifestyle), or, if sexually active, be practicing an effective method of birth control (for example, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study
• Body mass index (BMI) between 18 and 30 kilogram per square meter (kg/m\^2) (inclusive), and body weight not less than 50 kilogram (kg)
• Systolic blood pressure (after the participant is supine for 5 minutes) between 90 and 150 millimeter of mercury (mmHg) (inclusive) and diastolic blood pressure not more than 90 mmHg
• Comfortable with self-administration of intranasal medication and able to follow instructions provided
• A 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function

You may not qualify if:

• Current significant psychiatric (mental disorders) disorder including but not limited to psychotic (a person exhibiting mental illness), bipolar, major depressive or anxiety disorder
• Clinically significant medical illness including (but not limited to) cardiac arrhythmias (irregular heart beat) or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias \[disorder of blood\]), lipid abnormalities, significant pulmonary (having to do with the lungs) disease, including bronchospastic respiratory disease, diabetes mellitus (disorder in which there is decreased insulin in the body or the body's insulin is not effective, resulting in high blood sugar, increased thirst and urine, and many other side effects), renal or hepatic insufficiency, thyroid disease, neurologic disease, infection, hypertension or vascular disorders, kidney or urinary tract disturbances, sleep apnea (breathing problems while sleeping), myasthenia gravis (disorder that causes muscles to get tired quickly), or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results
• Use of any prescription or nonprescription medication, within 14 days before the first scheduled dose of the study drug
• Anatomical or medical conditions that may delay delivery or absorption of study medication (for example. undergone facial reconstructions, structural or functional abnormalities of the nose or upper airway; obstructions or mucosal lesions (any visible local abnormality of the tissues of the skin) of the nostrils or nasal passages; undergone sinus (a depression or cavity formed by a bending or curving) surgery in the previous 2 years; or signs and symptoms of upper respiratory infection, rhinitis, active allergies, or has a history of frequent sinus infections or complications)
• Has an abnormal or deviated nasal septum (when the inner wall separating the two sides of the nose is off to one side) 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

Related Publications (1)

• Perez-Ruixo C, Rossenu S, Zannikos P, Nandy P, Singh J, Drevets WC, Perez-Ruixo JJ. Population Pharmacokinetics of Esketamine Nasal Spray and its Metabolite Noresketamine in Healthy Subjects and Patients with Treatment-Resistant Depression. Clin Pharmacokinet. 2021 Apr;60(4):501-516. doi: 10.1007/s40262-020-00953-4. Epub 2020 Oct 31.

  PMID: 33128208 DERIVED

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2014
• First Posted: May 2, 2014
• Study Start: March 1, 2014
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: July 25, 2014

Record last verified: 2014-07

Locations

BE (1)