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| ID | Type | Description | Link |
|---|---|---|---|
| ESKETINTRD1003 | Other Identifier | Janssen Research and Development, LLC | |
| 2013-005372-18 | EudraCT Number |
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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.
This is a Phase 1, open-label (all people know the identity of the intervention), single-center, and single-dose study of esketamine, in healthy elderly (Cohort 1) and adult (Cohort 2) participants. Cohort 1 will comprise of 14 healthy elderly participants (greater than or equal to [>=] 65 years) with at least 3 participants above >=75 years of age and Cohort 2 will comprise of 20 healthy adult participants (18 to 55 years of age, inclusive). The study comprises of 3 phases: a Screening phase, an open-label Treatment phase (consisting of 1 treatment period for Cohort 1 and 2 treatment periods for Cohort 2), and a Safety follow-up phase. The duration of Screening phase is of 3 weeks; duration of treatment period for cohort 1 is of 3 days and for cohort 2 is 3 - 5 days (In Treatment period 1: 5 days for the first 7 participants who will complete the additional urine and fecal collection up to 72 hours post dose and 3 days for the last 13 participants who will be discharged after 24 hours; in Treatment period 2: 3 days for all participants). A washout period of 5 to 10 days will separate each intranasal esketamine treatment regimen for Cohort 2. All participants in Cohort 1 will receive Treatment A (that is, esketamine 14 milligram [mg] will be self-administered as intranasal spray into each nostril under the direct supervision of the investigator or designee), whereas, all participants in Cohort 2 will receive Treatment A followed by Treatment B (that is, esketamine 14 mg will be self-administered as intranasal spray followed by self-administration of placebo solution after 5 and 10 minutes of esketamine administration into each nostril, under the direct supervision of the investigator or designee) in a fixed sequence. The total esketamine dose will be 28 mg for each regimen. Blood samples will be collected for evaluation of pharmacokinetic parameters pre-dose and until 24 hours post-dose for evaluation of pharmacokinetic parameters. Participants' safety will be monitored throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Participants will receive esketamine 14 milligram (mg) as intranasal spray into each nostril on Day 1. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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 |
|---|---|---|---|---|---|---|
| Merksem | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33128208 | Derived | 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. |
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| ID | Term |
|---|---|
| C000629870 | Esketamine |
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| 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. |
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| 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 |