Pharmacology
Conditions
Brief summary
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.
Detailed description
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.
Interventions
Fentanyl delivered at low, medium and high doses by sublingual spray (FSS)
DRUGFentanyl Citrate IV
Fentanyl Citrate 50 mcg, delivered intravenously
Sponsors
INSYS Therapeutics Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Meets protocol-specified criteria for qualification and contraception * Willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with restrictions related food, drink and medications * Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures
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: 1. the safety or well-being of the participant or study staff 2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding) 3. the analysis of results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose normalized AUC | within 24 hours (see detailed description) | Categories: AUC0-1, AUC0-inf, AUCtau |
| 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 | within 24 hours (see detailed description) | Categories: of Cmax (ARcmax), based on trough concentration (ARctrough), of AUCtau (ARauctau) |
| Dose normalized Cmax | within 24 hours (see detailed description) | — |
| 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 | within 24 hours (see detailed description) | 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) |
| Apparent elimination rate constant in the terminal phase by non-compartmental analysis | within 24 hours (see detailed description) | — |
Secondary
| Measure | Time frame |
|---|---|
| Participants with hypoxia requiring oxygen administration | within 24 hours |
| 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 |
| Participants with respiratory depression requiring the use of naloxone | within 24 hours |
Countries
United States
Outcome results
None listed