Trial Outcomes & Findings for Study to Determine the Tolerability, Safety and Pharmacokinetics of Ketorolac Tromethamine by Intranasal Administration in Healthy Volunteers (NCT NCT01363050)

NCT ID: NCT01363050

Last Updated: 2017-03-16

Results Overview

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 15 participants
• Primary outcome timeframe: Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 1 (morning doses)
• Results posted on: 2017-03-16

Participant Flow

January 9, 2006 - February 27, 2006; Clinical Unit

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	Ketorolac Tromethamine Ketorolac tromethamine : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
Overall Study STARTED	15
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Determine the Tolerability, Safety and Pharmacokinetics of Ketorolac Tromethamine by Intranasal Administration in Healthy Volunteers

Baseline characteristics by cohort

Measure	Ketorolac Tromethamine n=15 Participants Ketorolac tromethamine : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	31.7 years STANDARD_DEVIATION 10.4 • n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	10 Participants n=93 Participants
Region of Enrollment United Kingdom	15 participants n=93 Participants

PRIMARY outcome

Timeframe: Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 1 (morning doses)

Population: Two subjects were considered pharmacokinetic outliers and were excluded from the PK population.

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Outcome measures

Measure	Ketorolac Tromethamine n=13 Participants Ketorolac tromethamine (Day 1) : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
Cmax (the Maximum Observed Plasma Concentration)	1147.9 ng/mL Standard Deviation 186.0

PRIMARY outcome

Timeframe: Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 1 (morning doses)

Population: Two subjects were considered pharmacokinetic outliers and were excluded from the PK population.

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Outcome measures

Measure	Ketorolac Tromethamine n=13 Participants Ketorolac tromethamine (Day 1) : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
Tmax (the Time to Maximum Concentration)	1.000 hours Interval 1.0 to 7.92

PRIMARY outcome

Timeframe: Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 1 (morning doses)

Population: Two subjects were considered pharmacokinetic outliers and were excluded from the PK population.

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Outcome measures

Measure	Ketorolac Tromethamine n=13 Participants Ketorolac tromethamine (Day 1) : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
AUC 0-8h (the Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose)	4713.8 ng*hours/mL Standard Deviation 744.8

PRIMARY outcome

Timeframe: Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 3 (morning doses)

Population: Two subjects were considered pharmacokinetic outliers and were excluded from the PK population.

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Outcome measures

Measure	Ketorolac Tromethamine n=13 Participants Ketorolac tromethamine (Day 1) : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
Cmax,ss (the Maximum Observed Plasma Concentration at Steady State)	1382.6 ng/mL Standard Deviation 224.3

PRIMARY outcome

Timeframe: Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 3 (morning doses)

Population: Two subjects were considered pharmacokinetic outliers and were excluded from the PK population.

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Outcome measures

Measure	Ketorolac Tromethamine n=13 Participants Ketorolac tromethamine (Day 1) : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
Tmax,ss (the Time to Maximum Concentration at Steady State)	1.000 hours Interval 1.0 to 3.0

PRIMARY outcome

Timeframe: Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 3 (morning doses)

Population: Two subjects were considered pharmacokinetic outliers and were excluded from the PK population.

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Outcome measures

Measure	Ketorolac Tromethamine n=13 Participants Ketorolac tromethamine (Day 1) : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
Cmin,ss (the Minimum Observed Plasma Concentration at Steady State)	367.7 ng/mL Standard Deviation 67.7

PRIMARY outcome

Timeframe: Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 3 (morning doses)

Population: Two subjects were considered pharmacokinetic outliers and were excluded from the PK population.

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Outcome measures

Measure	Ketorolac Tromethamine n=13 Participants Ketorolac tromethamine (Day 1) : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
Tmin,ss (the Time to Minimum Concentration at Steady State)	0.000 hours Interval 0.0 to 8.0

PRIMARY outcome

Timeframe: Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 3 (morning doses)

Population: Two subjects were considered pharmacokinetic outliers and were excluded from the PK population.

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Outcome measures

Measure	Ketorolac Tromethamine n=13 Participants Ketorolac tromethamine (Day 1) : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
AUCτ (the Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady-state)	6379.2 ng*hours/mL Standard Deviation 1031.0

PRIMARY outcome

Timeframe: Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 3 (morning doses)

Population: Two subjects were considered pharmacokinetic outliers and were excluded from the PK population.

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Outcome measures

Measure	Ketorolac Tromethamine n=13 Participants Ketorolac tromethamine (Day 1) : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
MRT (the Mean Residence Time	3.368 hours Standard Deviation 0.056

Adverse Events

Ketorolac Tromethamine

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ketorolac Tromethamine n=15 participants at risk Ketorolac tromethamine : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
Eye disorders Lacrimation increased	13.3% 2/15 • Number of events 4 • 1 month and 3 weeks
Gastrointestinal disorders Lip dry	6.7% 1/15 • Number of events 1 • 1 month and 3 weeks
Gastrointestinal disorders Nausea	6.7% 1/15 • Number of events 1 • 1 month and 3 weeks
General disorders Catheter site haematoma	6.7% 1/15 • Number of events 1 • 1 month and 3 weeks
General disorders Feeling cold	6.7% 1/15 • Number of events 1 • 1 month and 3 weeks
Infections and infestations Rhinitis	6.7% 1/15 • Number of events 2 • 1 month and 3 weeks
Musculoskeletal and connective tissue disorders Myalgia	6.7% 1/15 • Number of events 1 • 1 month and 3 weeks
Nervous system disorders Dizziness	6.7% 1/15 • Number of events 1 • 1 month and 3 weeks
Nervous system disorders Headache	20.0% 3/15 • Number of events 4 • 1 month and 3 weeks
Nervous system disorders Paraesthesia	6.7% 1/15 • Number of events 1 • 1 month and 3 weeks
Psychiatric disorders Anxiety	6.7% 1/15 • Number of events 1 • 1 month and 3 weeks
Respiratory, thoracic and mediastinal disorders Nasal discomfort	26.7% 4/15 • Number of events 10 • 1 month and 3 weeks
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.7% 1/15 • Number of events 1 • 1 month and 3 weeks
Respiratory, thoracic and mediastinal disorders Sneezing	13.3% 2/15 • Number of events 2 • 1 month and 3 weeks
Respiratory, thoracic and mediastinal disorders Throat irritation	13.3% 2/15 • Number of events 3 • 1 month and 3 weeks
Vascular disorders Orthostatic hypotension	6.7% 1/15 • Number of events 1 • 1 month and 3 weeks

Additional Information

David Bregman, M.D., Ph.D.

Luitpold Pharmaceuticals, Inc.

Phone: 610-650-4200

Email: dbregman@lpicrd.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place