Pharmacokinetics
Conditions
Keywords
Area under curve, time to maximum concentration
Brief summary
Evaluate the effect of taking ketoconazole on sufentanil plasma concentrations following sublingual administration of sufentanil NanoTab.
Interventions
DRUGSufentanil NanoTab (SUF NT) 15 mcg
Period 1: One dose of SUF NT 15 mcg administered sublingually
DRUGKetoconazole 400 mg, sufentanil NanoTab (SUF NT) 15 mcg
Period 2: Ketoconazole 400 mg administered daily for three days, SUF NT 15 mcg co-administered sublingually on the third day
Sponsors
Talphera, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Non smoking * Ages 18 to 45 year, inclusive * BMI between 18 and 30
Exclusion criteria
* subjects taking any prescription or OTC medications or vitamins or supplements * pregnant females * subjects with pulmonary disease or sleep apnea
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC (0-inf) | 0 (pre-dose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 120, 180, 240, 360, 480, 600, 720, and 840 minutes, and 24 hours after dosing.24 hours | Total amount of sufentanil absorbed; After each dosing of Sufentanil NanoTab, serial blood samples will be taken at regular time points. |
| Cmax | 0 (pre-dose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 120, 180, 240, 360, 480, 600, 720, and 840 minutes, and 24 hours after dosing. | Maximum plasma concentration; After each dosing of Sufentanil NanoTab, serial blood samples will be taken at regular time points. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SUF NT 15 mcg Then 3 Days of Ketoconazole and SUF NT 15 mcg Period 1: SUF NT 15 mcg administered once sublingually. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT dosing to block the opioid effects of the sufentanil.
Period 2: Ketoconazole 400 mg given daily for three days. One SUF NT 15 mcg was also co-administered sublingually with the third (last) ketoconazole dose.
Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT dosing to block the opioid effects of the sufentanil. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Ketoconazole 400 mg and SUF NT 15 mcg | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | SUF NT 15 mcg Then 3 Days of Ketoconazole and SUF NT 15 mcg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 19 | 4 / 18 |
| serious Total, serious adverse events | 0 / 19 | 0 / 18 |
Outcome results
Primary
AUC (0-inf)
Total amount of sufentanil absorbed; After each dosing of Sufentanil NanoTab, serial blood samples will be taken at regular time points.
Time frame: 0 (pre-dose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 120, 180, 240, 360, 480, 600, 720, and 840 minutes, and 24 hours after dosing.24 hours
Population: 2 of the 19 subjects had incomplete PK data and were excluded from PK analysis (1 due to early withdrawal and 1 due to AE)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SUF NT 15 mcg | AUC (0-inf) | 126.47 h*pg/mL | Geometric Coefficient of Variation 46.42 |
| Ketoconazole 400 mg and SUF NT 15 mcg | AUC (0-inf) | 223.63 h*pg/mL | Geometric Coefficient of Variation 45.45 |
Primary
Cmax
Maximum plasma concentration; After each dosing of Sufentanil NanoTab, serial blood samples will be taken at regular time points.
Time frame: 0 (pre-dose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 120, 180, 240, 360, 480, 600, 720, and 840 minutes, and 24 hours after dosing.
Population: 2 of the 19 subjects had incomplete PK data and were excluded from PK analysis (1 due to early withdrawal and 1 due to AE)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SUF NT 15 mcg | Cmax | 39.95 pg/mL | Standard Deviation 18.57 |
| Ketoconazole 400 mg and SUF NT 15 mcg | Cmax | 46.00 pg/mL | Standard Deviation 16.5 |