Clinical trial NCT02641340: Fentanyl Sublingual Spray in Opioid Naive Participants
Official title: A Phase 1, Multiple Ascending Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Fentanyl Sublingual Spray in Opioid Naive Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacology
Lead sponsor: INSYS Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2015-12-29
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum concentration (Cmax)
timeFrame: within 24 hours (see detailed description)
measure: Time to reach peak or maximum concentration following drug administration (Tmax)
timeFrame: within 24 hours (see detailed description)
measure: Area under the concentration-time curve
timeFrame: within 24 hours (see detailed description)
measure: Apparent elimination rate constant in the terminal phase by non-compartmental analysis
timeFrame: within 24 hours (see detailed description)
measure: Corresponding half-life (t1/2)
timeFrame: within 24 hours (see detailed description)
measure: Trough concentration during multiple dosing prior to next dose (Ctrough)
timeFrame: within 24 hours (see detailed description)
measure: Accumulation ratios
timeFrame: within 24 hours (see detailed description)
measure: Dose normalized Cmax
timeFrame: within 24 hours (see detailed description)
measure: Dose normalized AUC
timeFrame: within 24 hours (see detailed description)
Secondary outcomes:
measure: Participants with respiratory depression requiring the use of naloxone
timeFrame: within 24 hours
measure: Participants with hypoxia requiring oxygen administration
timeFrame: within 24 hours
measure: Participants needing noninvasive respiratory maneuvers (e.g., jaw thrust, bag-valve mask) to improve respiratory status at any point during the study
timeFrame: within 24 hours
measure: Participants with hypotension requiring intervention
timeFrame: within 24 hours
Other outcomes:
Locations:
city: Pasadena
country: United States
facility: Lotus Clinical Research, Inc.
state: California
Study officials:
affiliation: INSYS Therapeutics Inc
name: Neha Parikh
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.