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| ID | Type | Description | Link |
|---|---|---|---|
| ESKETINTRD1007 | Other Identifier | Janssen Research and Development, LLC | |
| 2014-000534-38 | EudraCT Number |
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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.
This is a Phase 1, single-center, open -label (all people know the identity of the intervention) study of intranasal esketamine in two cohorts: Cohort 1 will be healthy participants assigned to a fixed treatment sequence and Cohort 2 will be participants with nasal rhinitis randomized to 1 of 2 treatment sequences. For all participants, the study comprises 3 phases: a Screening phase (up to 21 days), an Open Label Treatment phase (includes 2 treatment periods; Period 1 and Period 2) and Follow-up phase (10 +/-2 days after last dose of esketamine).
Total study duration for participants in Cohort 1 is up to 52 days which includes Screening phase, Period 1 (3 days) where participants will self-administer a 56 milligram (mg) intranasal dose of esketamine solution on Day 1 and Period 2 (16 days) where participants will self-administer 200 microgram (mcg) of intranasal mometasone suspension on Day 1 (which will begin immediately following the 30 hour pharmacokinetic sample of Period 1) to Day 15, and then 200 mcg of intranasal mometasone suspension prior to a 56 mg dose of intranasal esketamine solution on Day 16 and the follow-up phase. Total study duration for participants in Cohort 2 is up to 44 days which includes Screening phase, Period 1 and Period 2 each of 3 days with a washout period of 5 to 10 days in-between esketamine dosing, and the follow-up phase. Cohort 2 participants will be randomly assigned to either treatment Sequence 1 or 2, wherein Sequence 1 comprises a 56 mg intranasal dose of esketamine solution alone in period 1 followed by period 2 which comprises a pretreatment with oxymetazoline 0.05 percent (%) weight by volume (w/v) solution 1 hour before administration of a 56 mg intranasal dose of esketamine solution. Sequence 2 comprises of a pretreatment with oxymetazoline 0.05 % w/v solution 1 hour before administration of a 56 mg intranasal dose of esketamine solution in Period 1 followed by period 2 which comprises a 56 mg intranasal dose of esketamine solution alone. Blood samples will be collected for evaluation of pharmacokinetic parameters of intranasal esketamine in healthy participants and participants with allergic rhinitis. Participants' safety will be monitored throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| 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). |
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| 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hanover | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37402024 | Derived | 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. |
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| 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. |
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| 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. |
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| Screening Up to 10 days after last study drug administration in Cohort 1 and Cohort 2 |
| ID | Term |
|---|---|
| D065631 | Rhinitis, Allergic |
| ID | Term |
|---|---|
| D012220 | Rhinitis |
| D009668 | Nose Diseases |
| D012140 | Respiratory Tract Diseases |
| D012130 | Respiratory Hypersensitivity |
| D010038 | Otorhinolaryngologic Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000629870 | Esketamine |
| D000068656 | Mometasone Furoate |
| D010109 | Oxymetazoline |
| ID | Term |
|---|---|
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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