Trial Outcomes & Findings for The Pharmacokinetics of Ketorolac Tromethamine Administered Intranasally (IN) for Postoperative Pain in Children Aged 12 Through 17 Years (NCT NCT01363076)
NCT ID: NCT01363076
Last Updated: 2017-03-16
Results Overview
Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
COMPLETED
PHASE1
20 participants
All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
2017-03-16
Participant Flow
Recruitment Period: June 2007 - January 2008; Location: Stanford University Medical Center
Screening procedure consisting of an interview and the following assessments: demographics, medical history, physical examination, concomitant medications within last 30 days, vital signs, clinical laboratory tests, pregnancy test (female subjects).
Participant milestones
| Measure |
Ketorolac Tromethamine (15 mg)
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
13
|
|
Overall Study
COMPLETED
|
7
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Ketorolac Tromethamine (15 mg)
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
The Pharmacokinetics of Ketorolac Tromethamine Administered Intranasally (IN) for Postoperative Pain in Children Aged 12 Through 17 Years
Baseline characteristics by cohort
| Measure |
Ketorolac Tromethamine (15 mg)
n=7 Participants
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
n=13 Participants
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
7 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
14.1 years
STANDARD_DEVIATION 0.7 • n=5 Participants
|
15.4 years
STANDARD_DEVIATION 1.6 • n=7 Participants
|
15.0 years
STANDARD_DEVIATION 1.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
13 participants
n=7 Participants
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dosePharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Ketorolac Tromethamine (15 mg)
n=7 Participants
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
n=13 Participants
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
Cmax (the Maximum Observed Plasma Concentration)
|
1153.9 ng/mL
Standard Deviation 485.0
|
1625.3 ng/mL
Standard Deviation 538.5
|
PRIMARY outcome
Timeframe: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dosePharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Pro. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac. Individual plasma ketorolac concentrations were summarized by dose level for the PK population at each sampling time using n, arithmetic mean, SD, CV(%), geometric mean, 95% confidence intervals (CI) for the arithmetic mean, median, minimum, and maximum.
Outcome measures
| Measure |
Ketorolac Tromethamine (15 mg)
n=7 Participants
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
n=13 Participants
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
Tmax (The Time to Maximum Observed Plasma Concentration; ie. The Time at Which Cmax Occured)
|
0.720 hr
Interval 0.38 to 6.07
|
0.780 hr
Interval 0.48 to 5.0
|
PRIMARY outcome
Timeframe: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dosePharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Ketorolac Tromethamine (15 mg)
n=7 Participants
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
n=13 Participants
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
AUClast (the Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Timepoint Post-dose)
|
9308.2 ng•h/mL
Standard Deviation 6214.2
|
10662.1 ng•h/mL
Standard Deviation 5383.5
|
PRIMARY outcome
Timeframe: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dosePharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Pro. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac. AUCinf calculated as: AUCinf = AUC(0-24) + (concentration at 24 hr/elimination constant).
Outcome measures
| Measure |
Ketorolac Tromethamine (15 mg)
n=6 Participants
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
n=12 Participants
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
AUCinf (the AUC Time From Zero to Infinity, Where Possible)
|
10590.7 ng•h/mL
Standard Deviation 7818.4
|
11949.5 ng•h/mL
Standard Deviation 6506.1
|
PRIMARY outcome
Timeframe: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dosePharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Ketorolac Tromethamine (15 mg)
n=7 Participants
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
n=12 Participants
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
AUC 0-24 (the AUC From Time Zero to 24 Hours Post-dose
|
9600.5 ng•h/mL
Standard Deviation 5959.9
|
11317.2 ng•h/mL
Standard Deviation 5666.1
|
PRIMARY outcome
Timeframe: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dosePharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Ketorolac Tromethamine (15 mg)
n=6 Participants
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
n=12 Participants
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
t1/2 (the Terminal Half-life, Where Possible)
|
6.678 hr
Standard Deviation 2.882
|
5.031 hr
Standard Deviation 2.055
|
PRIMARY outcome
Timeframe: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dosePharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Ketorolac Tromethamine (15 mg)
n=6 Participants
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
n=12 Participants
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
MRT (Mean Residence Time)
|
9.664 hr
Standard Deviation 3.892
|
6.727 hr
Standard Deviation 1.945
|
Adverse Events
Ketorolac Tromethamine (15 mg)
Ketorolac Tromethamine (30 mg)
Serious adverse events
| Measure |
Ketorolac Tromethamine (15 mg)
n=7 participants at risk
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
n=13 participants at risk
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/7 • 7 months
|
7.7%
1/13 • Number of events 1 • 7 months
|
Other adverse events
| Measure |
Ketorolac Tromethamine (15 mg)
n=7 participants at risk
Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.
|
Ketorolac Tromethamine (30 mg)
n=13 participants at risk
Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
14.3%
1/7 • Number of events 1 • 7 months
|
7.7%
1/13 • Number of events 1 • 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
|
28.6%
2/7 • Number of events 2 • 7 months
|
7.7%
1/13 • Number of events 1 • 7 months
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/7 • 7 months
|
7.7%
1/13 • Number of events 1 • 7 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/7 • 7 months
|
15.4%
2/13 • Number of events 2 • 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinalgia
|
0.00%
0/7 • 7 months
|
7.7%
1/13 • Number of events 1 • 7 months
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/7 • 7 months
|
15.4%
2/13 • Number of events 2 • 7 months
|
Additional Information
David Bregman, M.D., Ph.D.
Luitpold Pharmaceuticals, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place