Study to Assess the Effects of Allergic Rhinitis and Co-administration of Mometasone or Oxymetazoline on the Pharmacokinetics, Safety, and Tolerability of Intranasal Esketamine

NCT02154334 | Completed Phase 1

• 3 other identifiers: CR104359ESKETINTRD10072014-000534-38
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effects of allergic rhinitis (group of symptoms affecting the nose) and co-administration of mometasone or oxymetazoline on the pharmacokinetics (explores what the body does to the drug), safety, and tolerability of intranasal (administered through the nose) esketamine.

Conditions

Allergic Rhinitis

Keywords

Allergic Rhinitis; Healthy; Esketamine; Mometasone; Oxymetazoline; Phase 1

Outcome Measures

Primary Outcomes (5)

• Maximum Plasma Concentration (Cmax)

  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, 24 and 30 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, 24 and 30 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, 24 and 30 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, 24 and 30 hours after study drug administration

• Number of participants with adverse events (AEs) and serious adverse events (SAEs)

  An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product and does not necessarily have a causal relationship with the treatment. An SAE is any untoward medical occurrence that meets any of the following conditions: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

  Screening Up to 10 days after last study drug administration in Cohort 1 and Cohort 2

Study Arms (3)

Cohort 1

EXPERIMENTAL

One Intranasal spray of 14 milligram (mg) esketamine solution in each nostril on Day 1 at time 0 and 5 minutes (total esketamine dose will be 56 mg) in Period 1 (Treatment A). Two intranasal sprays of 50 microgram (mcg) mometasone suspension in each nostril for a total dose of 200 mcg on days 1 to 15 and 2 intranasal sprays of 50 mcg mometasone suspension in each nostril for a total dose of 200 mcg at time -1 hour prior to 1 intranasal spray of 14 mg esketamine solution in each nostril at time 0 and 5 minutes, for a total dose of 56 mg on Day 16 in Period 2 (Treatment B).

Drug: Esketamine; Drug: Mometasone

Cohort 2: Sequence 1

EXPERIMENTAL

One Intranasal spray of 14 mg esketamine solution in each nostril at time 0 and 5 minutes (total esketamine dose will be 56 mg) in Period 1 (Treatment A) and pretreatment with 2 sprays of oxymetazoline 0.05 percent (%) weight by volume (w/v) solution in each nostril at time -1 hour before administration of 1 Intranasal spray of 14 mg esketamine solution in each nostril at time 0 and 5 minutes, for a total dose of 56 mg in Period 2 (Treatment C).

Drug: Esketamine; Drug: Oxymetazoline

Cohort 2: Sequence 2

EXPERIMENTAL

Pretreatment with 2 sprays of oxymetazoline 0.05 percent (%) weight by volume (w/v) solution in each nostril at time -1 hour before administration of 1 Intranasal spray of 14 mg esketamine solution in each nostril at time 0 and 5 minutes, for a total dose of 56 mg in Period 1 (Treatment C) and 1 Intranasal spray of 14 mg esketamine solution in each nostril at time 0 and 5 minutes (total esketamine dose will be 56 mg) in Period 2 (Treatment A).

Drug: Esketamine; Drug: Oxymetazoline

Interventions

Esketamine DRUG

Participants will self-administer one Intranasal spray of 14 mg esketamine solution in each nostril on Day 1 at time 0 and 5 minutes (total esketamine dose will be 56 mg) in Period 1 and Period 2.

Cohort 1; Cohort 2: Sequence 1; Cohort 2: Sequence 2

Mometasone DRUG

Healthy participants will self-administer 2 intranasal sprays of 50 mcg mometasone suspension in each nostril for a total dose of 200 mcg on days 1 to 15 and 2 intranasal sprays of 50 mcg mometasone suspension in each nostril prior to 1 intranasal spray of esketamine solution 14 mg in each nostril at Time 0 and 5 minutes for a total dose of 56 mg on Day 16 in Period 2.

Cohort 1

Oxymetazoline DRUG

Nasal rhinitis participants will self-administer 2 intranasal sprays of Oxymetazoline 0.05% w/v solution in each nostril at time -1 hour before administration of 1 Intranasal spray of 14 mg esketamine solution in each nostril at time 0 and 5 minutes, for a total dose of 56 mg in Period 1or Period 2.

Cohort 2: Sequence 1; Cohort 2: Sequence 2

Eligibility Criteria

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

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 140 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
• For Cohort 2, participants should have a history of allergic rhinitis and a positive prick test for grass pollen at screening
• For Cohort 2, participants must have a Total Nasal Symptoms Score (TNSS) greater than or equal to (\>=) 6 with a nasal congestion score of \>=2 (minimum for "moderate rhinitis") on at least one occasion while participants are in the ECC during screening

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 \[Cohort 1 only\], active allergies \[Cohort 1 only\], 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

Hanover, Germany

Location

Related Publications (1)

• Zannikos P, Solanki B, De Meulder M, Badorrek P, Hohlfeld JM, Singh J. Pharmacokinetics of Nasal Esketamine in Patients with Allergic Rhinitis with and Without Nasal Decongestant Pretreatment and in Healthy Subjects with and Without Nasal Corticosteroid Pretreatment. Clin Pharmacokinet. 2023 Sep;62(9):1315-1328. doi: 10.1007/s40262-023-01273-z. Epub 2023 Jul 4.

  PMID: 37402024 DERIVED

MeSH Terms

Conditions

Rhinitis, Allergic

Interventions

Esketamine; Mometasone Furoate; Oxymetazoline

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2014
• First Posted: June 3, 2014
• Study Start: June 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: December 24, 2015

Record last verified: 2015-12

Locations

DE (1)