Trial Outcomes & Findings for Study to Assess the Absorption and Tolerability of Intranasal Ketorolac Tromethamine and to Assess the Effects of Oxymetazoline Hydrochloride and Fluticasone Propionate on the Absorption and Tolerability of Intranasal Ketorolac Tromethamine in Participants With Allergic Rhinitis (NCT NCT01365650)
NCT ID: NCT01365650
Last Updated: 2018-03-06
Results Overview
PK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.
COMPLETED
PHASE1
24 participants
Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethamine
2018-03-06
Participant Flow
December 18, 2007 through February 15, 2008; Medical Clinic
After subjects had given their informed consent, subjects were required to pass a screening visit within 3 weeks prior to study drug administration.
Participant milestones
| Measure |
Symptomatic Allergic Rhinitis
Treatment A: Single intranasal (i.n.) dose of Ketorolac tromethamine (KT) 30 mg (one 15 mg spray into each nostril) on day 1 of Period 1 followed by a 2-7 day washout interval Treatment B: Single i.n. dose of oxymetazoline hydrochloride (OH) followed 30 minutes later by a single i.n. dose of KT 30 mg (one 15 mg spray into each nostril) of Period 2 followed by a 2-7 day washout interval Treatment C: Seven days of treatment with i.n. fluticasone propionate (between Periods 2 and 3) followed by a single i.n. dose of KT 30 mg (one 15 mg spray into each nostril) on day 1 of Period 3
|
|---|---|
|
Treatment A
STARTED
|
24
|
|
Treatment A
COMPLETED
|
24
|
|
Treatment A
NOT COMPLETED
|
0
|
|
Treatment B
STARTED
|
24
|
|
Treatment B
COMPLETED
|
24
|
|
Treatment B
NOT COMPLETED
|
0
|
|
Treatment C
STARTED
|
24
|
|
Treatment C
COMPLETED
|
24
|
|
Treatment C
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Assess the Absorption and Tolerability of Intranasal Ketorolac Tromethamine and to Assess the Effects of Oxymetazoline Hydrochloride and Fluticasone Propionate on the Absorption and Tolerability of Intranasal Ketorolac Tromethamine in Participants With Allergic Rhinitis
Baseline characteristics by cohort
| Measure |
All Study Participants
n=24 Participants
Treatment A: Single intranasal (i.n.) dose of Ketorolac tromethamine (KT) 30 mg (one 15 mg spray into each nostril) on day 1 of Period 1 followed by a 2-7 day washout interval Treatment B: Single i.n. dose of oxymetazoline hydrochloride (OH) followed 30 minutes later by a single i.n. dose of KT 30 mg (one 15 mg spray into each nostril) of Period 2 followed by a 2-7 day washout interval Treatment C: Seven days of treatment with i.n. fluticasone propionate (between Periods 2 and 3) followed by a single i.n. dose of KT 30 mg (one 15 mg spray into each nostril) on day 1 of Period 3
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
42.6 years
STANDARD_DEVIATION 16.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethaminePK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Single i.n. Dose of 30 mg Ketorolac Tromethamine
n=24 Participants
Treatment A: Single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 1.
|
Single i.n. Dose of Oxymetazoline Hydrochloride Followed by a
n=24 Participants
Treatment B: Single i.n. dose of oxymetazoline hydrochloride followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) 30 minutes later on Day 1 of Period 2.
|
Seven Days of Treatment With i.n. Fluticasone Propionate
n=24 Participants
Treatment C: Seven days of treatment with i.n. fluticasone propionate (between Periods 2 and 3) followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 3.
|
|---|---|---|---|
|
Cmax (the Maximum Observed Plasma Concentration)
|
1630.223 ng/mL
Standard Deviation 653.599
|
1729.393 ng/mL
Standard Deviation 684.055
|
1617.810 ng/mL
Standard Deviation 766.328
|
PRIMARY outcome
Timeframe: Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethaminePK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Single i.n. Dose of 30 mg Ketorolac Tromethamine
n=24 Participants
Treatment A: Single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 1.
|
Single i.n. Dose of Oxymetazoline Hydrochloride Followed by a
n=24 Participants
Treatment B: Single i.n. dose of oxymetazoline hydrochloride followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) 30 minutes later on Day 1 of Period 2.
|
Seven Days of Treatment With i.n. Fluticasone Propionate
n=24 Participants
Treatment C: Seven days of treatment with i.n. fluticasone propionate (between Periods 2 and 3) followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 3.
|
|---|---|---|---|
|
Tmax (the Time to Maximum Concentration)
|
1.000 hours
Interval 0.25 to 2.0
|
1.250 hours
Interval 0.75 to 2.05
|
0.875 hours
Interval 0.25 to 4.0
|
PRIMARY outcome
Timeframe: Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethaminePK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Single i.n. Dose of 30 mg Ketorolac Tromethamine
n=24 Participants
Treatment A: Single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 1.
|
Single i.n. Dose of Oxymetazoline Hydrochloride Followed by a
n=24 Participants
Treatment B: Single i.n. dose of oxymetazoline hydrochloride followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) 30 minutes later on Day 1 of Period 2.
|
Seven Days of Treatment With i.n. Fluticasone Propionate
n=24 Participants
Treatment C: Seven days of treatment with i.n. fluticasone propionate (between Periods 2 and 3) followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 3.
|
|---|---|---|---|
|
AUC 0-t (the Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Time Point Post-dose)
|
9001.8 ng*h/mL
Standard Deviation 4011.2
|
9310.3 ng*h/mL
Standard Deviation 3200.2
|
8794.3 ng*h/mL
Standard Deviation 4188.2
|
PRIMARY outcome
Timeframe: Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethaminePK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Single i.n. Dose of 30 mg Ketorolac Tromethamine
n=24 Participants
Treatment A: Single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 1.
|
Single i.n. Dose of Oxymetazoline Hydrochloride Followed by a
n=24 Participants
Treatment B: Single i.n. dose of oxymetazoline hydrochloride followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) 30 minutes later on Day 1 of Period 2.
|
Seven Days of Treatment With i.n. Fluticasone Propionate
n=24 Participants
Treatment C: Seven days of treatment with i.n. fluticasone propionate (between Periods 2 and 3) followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 3.
|
|---|---|---|---|
|
AUC 0-∞ (the AUC From Time Zero to Infinity, Where Possible)
|
9906.9 ng*h/mL
Standard Deviation 4347.0
|
9959.1 ng*h/mL
Standard Deviation 3294.8
|
9445.4 ng*h/mL
Standard Deviation 4308.2
|
PRIMARY outcome
Timeframe: Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethaminePK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Single i.n. Dose of 30 mg Ketorolac Tromethamine
n=24 Participants
Treatment A: Single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 1.
|
Single i.n. Dose of Oxymetazoline Hydrochloride Followed by a
n=24 Participants
Treatment B: Single i.n. dose of oxymetazoline hydrochloride followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) 30 minutes later on Day 1 of Period 2.
|
Seven Days of Treatment With i.n. Fluticasone Propionate
n=24 Participants
Treatment C: Seven days of treatment with i.n. fluticasone propionate (between Periods 2 and 3) followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 3.
|
|---|---|---|---|
|
t1/2z (the Terminal Half-life, Where Possible)
|
5.583 hours
Standard Deviation 1.929
|
5.172 hours
Standard Deviation 1.582
|
5.216 hours
Standard Deviation 1.958
|
PRIMARY outcome
Timeframe: Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethaminePK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.
Outcome measures
| Measure |
Single i.n. Dose of 30 mg Ketorolac Tromethamine
n=24 Participants
Treatment A: Single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 1.
|
Single i.n. Dose of Oxymetazoline Hydrochloride Followed by a
n=24 Participants
Treatment B: Single i.n. dose of oxymetazoline hydrochloride followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) 30 minutes later on Day 1 of Period 2.
|
Seven Days of Treatment With i.n. Fluticasone Propionate
n=24 Participants
Treatment C: Seven days of treatment with i.n. fluticasone propionate (between Periods 2 and 3) followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 3.
|
|---|---|---|---|
|
MRT (the Mean Residence Time)
|
7.241 hours
Standard Deviation 2.235
|
6.861 hours
Standard Deviation 2.037
|
7.088 hours
Standard Deviation 2.488
|
Adverse Events
Single i.n. Dose of 30 mg Ketorolac Tromethamine
Single i.n. Dose of Oxymetazoline Hydrochloride Followed by a
Seven Days of Treatment With i.n. Fluticasone Propionate
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Single i.n. Dose of 30 mg Ketorolac Tromethamine
n=24 participants at risk
Treatment A: Single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 1.
|
Single i.n. Dose of Oxymetazoline Hydrochloride Followed by a
n=24 participants at risk
Treatment B: Single i.n. dose of oxymetazoline hydrochloride followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) 30 minutes later on Day 1 of Period 2.
|
Seven Days of Treatment With i.n. Fluticasone Propionate
n=24 participants at risk
Treatment C: Seven days of treatment with i.n. fluticasone propionate (between Periods 2 and 3) followed by a single i.n. dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on day 1 of Period 3.
|
|---|---|---|---|
|
Eye disorders
Lacrimation increased
|
12.5%
3/24 • Number of events 3 • 3 months
|
0.00%
0/24 • 3 months
|
8.3%
2/24 • Number of events 2 • 3 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/24 • 3 months
|
12.5%
3/24 • Number of events 4 • 3 months
|
0.00%
0/24 • 3 months
|
|
Infections and infestations
Urinary tract infection
|
8.3%
2/24 • Number of events 2 • 3 months
|
0.00%
0/24 • 3 months
|
8.3%
2/24 • Number of events 2 • 3 months
|
|
Nervous system disorders
Dizziness
|
8.3%
2/24 • Number of events 2 • 3 months
|
4.2%
1/24 • Number of events 1 • 3 months
|
4.2%
1/24 • Number of events 1 • 3 months
|
|
Nervous system disorders
Headache
|
12.5%
3/24 • Number of events 3 • 3 months
|
12.5%
3/24 • Number of events 3 • 3 months
|
8.3%
2/24 • Number of events 2 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.2%
1/24 • Number of events 1 • 3 months
|
4.2%
1/24 • Number of events 1 • 3 months
|
8.3%
2/24 • Number of events 2 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
4.2%
1/24 • Number of events 1 • 3 months
|
8.3%
2/24 • Number of events 2 • 3 months
|
0.00%
0/24 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
33.3%
8/24 • Number of events 8 • 3 months
|
4.2%
1/24 • Number of events 1 • 3 months
|
20.8%
5/24 • Number of events 5 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
|
45.8%
11/24 • Number of events 12 • 3 months
|
75.0%
18/24 • Number of events 18 • 3 months
|
58.3%
14/24 • Number of events 14 • 3 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