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The primary objective of this trial is to determine the pharmacokinetic and pharmacodynamic relationship of multiple dose administration of fentanyl sublingual spray in opioid naive participants. The secondary objective is to determine the safety and tolerability of multiple dose administration of fentanyl sublingual spray in opioid naive subjects.
For all cycles, blood will be drawn according to the following schedule:
The 0 time (pre-dose) blood sample will be collected within 60 minutes prior to first study drug administration.
Cohort l: 0 (pre-dose), 5, 15 and 30 minutes after the first dose and at 1, 2, 4 (prior to second-dose), 4.083, 4.25, 4.5, 5, 6, 8 (prior to third-dose), 8.083, 8.25, 8.5, 9, 10, 12, 16 and 24 hours after the first dose.
Cohort 2: 0 (pre-dose), 5, 15 and 30 minutes after the first dose and at 1, 2 (prior to second-dose), 2.083, 2.25, 2.5, 3, 4 (prior to third-dose), 4.083, 4.25, 4.5, 5, 6, 8, 10, 12, 16 and 24 hours after the first dose.
Cohort 3: 0 (pre-dose), 5, 15, 30 and 45 minutes after the first dose and at 1 (prior to second-dose), 1.083, 1.25, l.5, 1.75, 2 (prior to third-dose), 2.083, 2.25, 2.5, 2.75, 3, 4, 8, 12, 16 and 24 hours after the first dose.
Cohort 4: 0 (pre-dose), 5, 15, 30 (prior to the second-dose), 35, and 45 minutes after the first dose and at I (prior to the third-dose), 1.083, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 4, 8, 12, 16 and 24 hours after the first dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cycle 1, Cohort 1 | Experimental | Fentanyl Sublingual Spray (FSS) low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every four hours for a maximum of three doses. |
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| Cycle 1, Cohort 2 | Experimental | FSS low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every two hours for a maximum of three doses. |
|
| Cycle 1, Cohort 3 | Experimental | FSS low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every hour for a maximum of three doses. |
|
| Cycle 1, Cohort 4 | Experimental | FSS low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every 30 minutes for a maximum of three doses. |
|
| Cycle 2, Cohort 1 | Experimental | FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every four hours for a maximum of three doses. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fentanyl Sublingual Spray | Drug | Fentanyl delivered at low, medium and high doses by sublingual spray (FSS) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum concentration (Cmax) | within 24 hours (see detailed description) | |
| Time to reach peak or maximum concentration following drug administration (Tmax) | within 24 hours (see detailed description) | |
| Area under the concentration-time curve | Categories: during a dosing interval (AUCtau ), from the time of dosing to infinity (AUC0-inf), from the time of dosing to the last quantifiable time point (AUC0-t) | within 24 hours (see detailed description) |
| Apparent elimination rate constant in the terminal phase by non-compartmental analysis | within 24 hours (see detailed description) | |
| Corresponding half-life (t1/2) | within 24 hours (see detailed description) | |
| Trough concentration during multiple dosing prior to next dose (Ctrough) | within 24 hours (see detailed description) | |
| Accumulation ratios | Categories: of Cmax (ARcmax), based on trough concentration (ARctrough), of AUCtau (ARauctau) | within 24 hours (see detailed description) |
| Dose normalized Cmax | within 24 hours (see detailed description) | |
| Dose normalized AUC | Categories: AUC0-1, AUC0-inf, AUCtau |
| Measure | Description | Time Frame |
|---|---|---|
| Participants with respiratory depression requiring the use of naloxone | within 24 hours | |
| Participants with hypoxia requiring oxygen administration | within 24 hours | |
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Inclusion Criteria:
Exclusion Criteria:
History or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters
Signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:
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| Name | Affiliation | Role |
|---|---|---|
| Neha Parikh | INSYS Therapeutics Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lotus Clinical Research, Inc. | Pasadena | California | 91105 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29909433 | Derived | Rauck RL, Oh DA, Singla N, Koch C, Parikh N, Nalamachu S, Yu J, James S. Pharmacokinetics of Fentanyl Sublingual Spray in Opioid-Naive Participants: Results of a Phase 1, Multiple Ascending Dose Study. Clin Drug Investig. 2018 Aug;38(8):715-726. doi: 10.1007/s40261-018-0658-9. | |
| 28942715 | Derived | Rauck RL, Oh DA, Singla N, Koch C, Parikh N, Nalamachu S, Wilson D, Yu J, Vetticaden S. Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a multiple ascending dose study in opioid-naive healthy volunteers. Curr Med Res Opin. 2017 Nov;33(11):1921-1933. doi: 10.1080/03007995.2017.1371681. Epub 2017 Sep 23. |
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| ID | Term |
|---|---|
| D005283 | Fentanyl |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Cycle 2, Cohort 2 | Experimental | FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every two hours for a maximum of three doses. |
|
| Cycle 2, Cohort 3 | Experimental | FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every hour for a maximum of three doses. |
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| Cycle 2, Cohort 4 | Experimental | FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every 30 minutes for a maximum of three doses. |
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| Cycle 3, Cohort 1 | Experimental | FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every four hours for a maximum of three doses. |
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| Cycle 3, Cohort 2 | Experimental | FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every two hours for a maximum of three doses. |
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| Cycle 3, Cohort 3 | Experimental | FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every hour for a maximum of three doses. |
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| Cycle 3, Cohort 4 | Experimental | FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every 30 minutes for a maximum of three doses. |
|
|
| Fentanyl Citrate IV | Drug | Fentanyl Citrate 50 mcg, delivered intravenously |
|
| within 24 hours (see detailed description) |
| Participants needing noninvasive respiratory maneuvers (e.g., jaw thrust, bag-valve mask) to improve respiratory status at any point during the study |
| within 24 hours |
| Participants with hypotension requiring intervention | within 24 hours |