Trial Outcomes & Findings for Open Label Crossover Study Pharmacokinetics (PK) Study in Healthy Volunteers Receiving Various Forms of Fentanyl (NCT NCT02470390)
NCT ID: NCT02470390
Last Updated: 2018-03-16
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
13 participants
Primary outcome timeframe
6 hrs (pre-dose, 5, 10, 20, 30, 45, & 60 min, and 2, 3, 4, & 6 hrs post-dose on Study Days 1 & 3)
Results posted on
2018-03-16
Participant Flow
A total of 13 healthy subjects were randomly assigned to treatment in this crossover study: 6 in the "Nasal Fentanyl First, then Sublingual Fentanyl and IV Fentanyl" arm and 7 in the "Sublingual Fentanyl First, then Nasal Fentanyl and IV Fentanyl" arm.
Participant milestones
| Measure |
Nasal Fentanyl First, Then Sublingual Fentanyl and IV Fentanyl
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 per protocol.
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 3 per protocol.
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
Sublingual Fentanyl First, Then Nasal Fentanyl and IV Fentanyl
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 per protocol.
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 3 per protocol.
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
7
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Open Label Crossover Study Pharmacokinetics (PK) Study in Healthy Volunteers Receiving Various Forms of Fentanyl
Baseline characteristics by cohort
| Measure |
Nasal Fentanyl First, Then Sublingual Fentanyl and IV Fentanyl
n=6 Participants
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 per protocol.
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 3 per protocol.
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
Sublingual Fentanyl First, Then Nasal Fentanyl and IV Fentanyl
n=7 Participants
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 per protocol.
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 3 per protocol.
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.0 years
STANDARD_DEVIATION 14.38 • n=5 Participants
|
43.0 years
STANDARD_DEVIATION 9.50 • n=7 Participants
|
41.2 years
STANDARD_DEVIATION 11.65 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 hrs (pre-dose, 5, 10, 20, 30, 45, & 60 min, and 2, 3, 4, & 6 hrs post-dose on Study Days 1 & 3)Population: The CSF PK population included all subjects who completed all study periods and Cmax was less than 5% pre-dose. The above CSF PK outcome compares nasal and sublingual fentanyl interventions.
Outcome measures
| Measure |
Nasal Fentanyl
n=10 Participants
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 or 3 per protocol.
|
Sublingual Fentanyl
n=9 Participants
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 or 3 per protocol.
|
IV Fentanyl
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Concentration (Tmax) of Fentanyl in Cerebrospinal Fluid (CSF) (1 of 3)
|
1.01 h
Interval 0.75 to 3.0
|
2.00 h
Interval 0.75 to 3.0
|
—
|
PRIMARY outcome
Timeframe: 6 hrs (pre-dose, 5, 10, 20, 30, 45, & 60 min, and 2, 3, 4, & 6 hrs post-dose on Study Days 1 & 3)Population: The CSF PK population included all subjects who completed all study periods and Cmax was less than 5% pre-dose. The above CSF PK outcome compares nasal and sublingual fentanyl interventions.
Outcome measures
| Measure |
Nasal Fentanyl
n=10 Participants
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 or 3 per protocol.
|
Sublingual Fentanyl
n=9 Participants
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 or 3 per protocol.
|
IV Fentanyl
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of Fentanyl in Cerebrospinal Fluid (CSF) (2 of 3)
|
84.54 pg/mL
Standard Deviation 47.10
|
56.37 pg/mL
Standard Deviation 22.13
|
—
|
PRIMARY outcome
Timeframe: 6 hrs (pre-dose, 5, 10, 20, 30, 45, & 60 min, and 2, 3, 4, & 6 hrs post-dose on Study Days 1 & 3)Population: The CSF PK population included all subjects who completed all study periods and Cmax was less than 5% pre-dose. The above CSF PK outcome compares nasal and sublingual fentanyl interventions.
Outcome measures
| Measure |
Nasal Fentanyl
n=10 Participants
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 or 3 per protocol.
|
Sublingual Fentanyl
n=9 Participants
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 or 3 per protocol.
|
IV Fentanyl
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|---|
|
Area Under the Concentration-Time Curve From Hour 0 to Hour 6 (AUC 0-6h) of Fentanyl in Cerebrospinal Fluid (CSF) (3 of 3)
|
300.25 pg*h/mL
Standard Deviation 121.93
|
221.49 pg*h/mL
Standard Deviation 76.82
|
—
|
PRIMARY outcome
Timeframe: 24 hrs (pre-dose, 5, 10, 15, 20, 30, 45, & 60 min, and 1.5, 2, 3, 4, 6, 8, 12, & 24 hrs on Study Days 1 & 3 for Nasal Fentanyl / Sublingual Fentanyl; pre-dose, 2, 5, 10, 20, 30, & 60 min, and 2, 4, 6, 8, 12, & 24 hrs on Study Day 5 for IV Fentanyl)Population: The Plasma PK population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable PK parameter.
Cmax (pg/mL)
Outcome measures
| Measure |
Nasal Fentanyl
n=12 Participants
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 or 3 per protocol.
|
Sublingual Fentanyl
n=13 Participants
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 or 3 per protocol.
|
IV Fentanyl
n=12 Participants
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of Fentanyl in Plasma (1 of 5)
|
541.28 pg/mL
Geometric Coefficient of Variation 78.1
|
369.59 pg/mL
Geometric Coefficient of Variation 41.4
|
1166.51 pg/mL
Geometric Coefficient of Variation 130.8
|
PRIMARY outcome
Timeframe: 24 hrs (pre-dose, 5, 10, 15, 20, 30, 45, & 60 min, and 1.5, 2, 3, 4, 6, 8, 12, & 24 hrs on Study Days 1 & 3 for Nasal Fentanyl / Sublingual Fentanyl; pre-dose, 2, 5, 10, 20, 30, & 60 min, and 2, 4, 6, 8, 12, & 24 hrs on Study Day 5 for IV Fentanyl)Population: The Plasma PK population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable PK parameter.
AUC 0-tlast (pg\*h/mL)
Outcome measures
| Measure |
Nasal Fentanyl
n=12 Participants
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 or 3 per protocol.
|
Sublingual Fentanyl
n=13 Participants
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 or 3 per protocol.
|
IV Fentanyl
n=12 Participants
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|---|
|
Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUC 0-tlast) of Fentanyl in Plasma (2 of 5)
|
2752.51 pg*h/mL
Geometric Coefficient of Variation 37.3
|
2359.08 pg*h/mL
Geometric Coefficient of Variation 27.5
|
2236.46 pg*h/mL
Geometric Coefficient of Variation 26.5
|
PRIMARY outcome
Timeframe: 24 hrs (pre-dose, 5, 10, 15, 20, 30, 45, & 60 min, and 1.5, 2, 3, 4, 6, 8, 12, & 24 hrs on Study Days 1 & 3 for Nasal Fentanyl / Sublingual Fentanyl; pre-dose, 2, 5, 10, 20, 30, & 60 min, and 2, 4, 6, 8, 12, & 24 hrs on Study Day 5 for IV Fentanyl)Population: The Plasma PK population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable PK parameter. The AUC 0-inf values were excluded where %AUC extrap was greater than 20%.
AUC 0-inf (pg\*h/mL)
Outcome measures
| Measure |
Nasal Fentanyl
n=6 Participants
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 or 3 per protocol.
|
Sublingual Fentanyl
n=7 Participants
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 or 3 per protocol.
|
IV Fentanyl
n=3 Participants
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|---|
|
Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) of Fentanyl in Plasma (3 of 5)
|
3413.80 pg*h/mL
Geometric Coefficient of Variation 34.8
|
2879.85 pg*h/mL
Geometric Coefficient of Variation 26.0
|
2871.89 pg*h/mL
Geometric Coefficient of Variation 17.7
|
PRIMARY outcome
Timeframe: 24 hrs (pre-dose, 5, 10, 15, 20, 30, 45, & 60 min, and 1.5, 2, 3, 4, 6, 8, 12, & 24 hrs on Study Days 1 & 3 for Nasal Fentanyl / Sublingual Fentanyl; pre-dose, 2, 5, 10, 20, 30, & 60 min, and 2, 4, 6, 8, 12, & 24 hrs on Study Day 5 for IV Fentanyl)Population: The Plasma PK population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable PK parameter.
Tmax (h)
Outcome measures
| Measure |
Nasal Fentanyl
n=12 Participants
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 or 3 per protocol.
|
Sublingual Fentanyl
n=13 Participants
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 or 3 per protocol.
|
IV Fentanyl
n=12 Participants
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Concentration (Tmax) of Fentanyl in Plasma (4 of 5)
|
0.63 h
Interval 0.17 to 2.0
|
0.75 h
Interval 0.25 to 4.0
|
0.07 h
Interval 0.03 to 1.0
|
PRIMARY outcome
Timeframe: 24 hrs (pre-dose, 5, 10, 15, 20, 30, 45, & 60 min, and 1.5, 2, 3, 4, 6, 8, 12, & 24 hrs on Study Days 1 & 3 for Nasal Fentanyl / Sublingual Fentanyl; pre-dose, 2, 5, 10, 20, 30, & 60 min, and 2, 4, 6, 8, 12, & 24 hrs on Study Day 5 for IV Fentanyl)Population: The Plasma PK population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable PK parameter.
t1/2 (h)
Outcome measures
| Measure |
Nasal Fentanyl
n=10 Participants
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 or 3 per protocol.
|
Sublingual Fentanyl
n=12 Participants
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 or 3 per protocol.
|
IV Fentanyl
n=6 Participants
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|---|
|
Terminal Elimination Half-Life (t1/2) of Fentanyl in Plasma (5 of 5)
|
12.08 h
Geometric Coefficient of Variation 40.0
|
10.73 h
Geometric Coefficient of Variation 39.6
|
12.25 h
Geometric Coefficient of Variation 24.2
|
Adverse Events
Nasal Fentanyl
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Sublingual Fentanyl
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
IV Fentanyl
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Nasal Fentanyl
n=12 participants at risk
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 or 3 per protocol.
|
Sublingual Fentanyl
n=13 participants at risk
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 or 3 per protocol.
|
IV Fentanyl
n=12 participants at risk
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Post Lumbar Puncture Syndrome
|
0.00%
0/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
7.7%
1/13 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
Other adverse events
| Measure |
Nasal Fentanyl
n=12 participants at risk
Nasal Fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute on Study Day 1 or 3 per protocol.
|
Sublingual Fentanyl
n=13 participants at risk
Sublingual Fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue on Study Day 1 or 3 per protocol.
|
IV Fentanyl
n=12 participants at risk
IV Fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes on Study Day 5 per protocol.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
23.1%
3/13 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
|
Gastrointestinal disorders
Abdominal Distension
|
8.3%
1/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/13 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/13 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
|
Nervous system disorders
Headache
|
16.7%
2/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
7.7%
1/13 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
|
Nervous system disorders
Radicular Pain
|
0.00%
0/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
7.7%
1/13 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
|
General disorders
Catheter Site Pain
|
8.3%
1/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/13 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
8.3%
1/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
7.7%
1/13 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
0.00%
0/12 • 8 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PI agrees that sponsor shall have the right to the first publication of the study results which is intended to be a joint, multi-center publication. Following the first publication, the PI may publish study data or results, provided however PI submits the proposed publication to sponsor for review at least 60 days prior to the date of the proposed publication. Sponsor may remove any information that is considered confidential and / or proprietary other than study data.
- Publication restrictions are in place
Restriction type: OTHER