Trial Outcomes & Findings for Tolerability, Safety and Pharmacokinetics of Four Formulations of Ketorolac Tromethamine in Healthy Volunteers (NCT NCT01355588)

NCT ID: NCT01355588

Last Updated: 2017-03-16

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Results posted on

2017-03-16

Participant Flow

1 month and 2 weeks; Medeval Limited Skelton House, Manchester Science Park, Lloyd Street North, Manchester M15 6SH, U.K.

Participant milestones

Participant milestones
Measure
Treatment A, Treatment C, Treatment D, Treatment B
Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Treatment B, Treatment D, Treatment C, Treatment A
Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Treatment C, Treatment B, Treatment A, Treatment D
Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Treatment D, Treatment A, Treatment B, Treatment C
Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
First Intervention (Day 1)
STARTED
4
4
4
4
First Intervention (Day 1)
COMPLETED
4
4
4
4
First Intervention (Day 1)
NOT COMPLETED
0
0
0
0
Washout (3-7 Days)
STARTED
4
4
4
4
Washout (3-7 Days)
COMPLETED
4
4
4
4
Washout (3-7 Days)
NOT COMPLETED
0
0
0
0
Second Intervention (After Washout)
STARTED
4
4
4
4
Second Intervention (After Washout)
COMPLETED
4
4
4
4
Second Intervention (After Washout)
NOT COMPLETED
0
0
0
0
Third Intervention (After Washout)
STARTED
4
4
4
4
Third Intervention (After Washout)
COMPLETED
4
4
4
4
Third Intervention (After Washout)
NOT COMPLETED
0
0
0
0
Fourth Intervention (After Washout)
STARTED
4
4
4
4
Fourth Intervention (After Washout)
COMPLETED
4
4
4
4
Fourth Intervention (After Washout)
NOT COMPLETED
0
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Tolerability, Safety and Pharmacokinetics of Four Formulations of Ketorolac Tromethamine in Healthy Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment A, Treatment C, Treatment D, Treatment B
n=4 Participants
Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Treatment B, Treatment D, Treatment C, Treatment A
n=4 Participants
Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Treatment C, Treatment B, Treatment A, Treatment D
n=4 Participants
Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Treatment D, Treatment A, Treatment B, Treatment C
n=4 Participants
Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
Total
n=16 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Age, Categorical
Between 18 and 65 years
4 Participants
n=5 Participants
4 Participants
n=7 Participants
4 Participants
n=5 Participants
4 Participants
n=4 Participants
16 Participants
n=21 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Age, Continuous
34.25 years
STANDARD_DEVIATION 17.21 • n=5 Participants
40.75 years
STANDARD_DEVIATION 19.97 • n=7 Participants
34.0 years
STANDARD_DEVIATION 15.90 • n=5 Participants
50.25 years
STANDARD_DEVIATION 10.31 • n=4 Participants
39.8 years
STANDARD_DEVIATION 16.0 • n=21 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
2 Participants
n=4 Participants
5 Participants
n=21 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
4 Participants
n=7 Participants
3 Participants
n=5 Participants
2 Participants
n=4 Participants
11 Participants
n=21 Participants
Region of Enrollment
United Kingdom
4 participants
n=5 Participants
4 participants
n=7 Participants
4 participants
n=5 Participants
4 participants
n=4 Participants
16 participants
n=21 Participants

PRIMARY outcome

Timeframe: Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Outcome measures

Outcome measures
Measure
Ketorolac Tromethamine
n=16 Participants
Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)
n=16 Participants
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Ketorolac Tromethamine With 5% Lidocaine HCl
n=16 Participants
Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
Ketorolac Tromethamine With 6% Lidocaine HCl
n=16 Participants
30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Maximum Observed Plasma Concentration (Cmax)
2059.6 ng/mL
Standard Deviation 801.7
1963.1 ng/mL
Standard Deviation 1020.8
1799.9 ng/mL
Standard Deviation 714.1
2048.5 ng/mL
Standard Deviation 817.6

PRIMARY outcome

Timeframe: Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Outcome measures

Outcome measures
Measure
Ketorolac Tromethamine
n=16 Participants
Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)
n=16 Participants
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Ketorolac Tromethamine With 5% Lidocaine HCl
n=16 Participants
Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
Ketorolac Tromethamine With 6% Lidocaine HCl
n=16 Participants
30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Post-dose (AUC 0-t)
8440.6 ng*h/mL
Standard Deviation 4021.2
7856.0 ng*h/mL
Standard Deviation 4211.8
7561.5 ng*h/mL
Standard Deviation 4051.2
8103.8 ng*h/mL
Standard Deviation 3786.3

PRIMARY outcome

Timeframe: Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Outcome measures

Outcome measures
Measure
Ketorolac Tromethamine
n=16 Participants
Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)
n=16 Participants
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Ketorolac Tromethamine With 5% Lidocaine HCl
n=16 Participants
Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
Ketorolac Tromethamine With 6% Lidocaine HCl
n=16 Participants
30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUC 0-∞)
9061.9 ng*h/mL
Standard Deviation 4526.8
8694.5 ng*h/mL
Standard Deviation 4477.1
8086.8 ng*h/mL
Standard Deviation 4608.2
8677.6 ng*h/mL
Standard Deviation 4301.0

SECONDARY outcome

Timeframe: Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Outcome measures

Outcome measures
Measure
Ketorolac Tromethamine
n=16 Participants
Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)
n=16 Participants
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Ketorolac Tromethamine With 5% Lidocaine HCl
n=16 Participants
Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
Ketorolac Tromethamine With 6% Lidocaine HCl
n=16 Participants
30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Time to Reach Maximum Plasma Concentration (Tmax)
0.510 hours
Interval 0.5 to 1.5
0.500 hours
Interval 0.25 to 4.0
0.390 hours
Interval 0.25 to 0.75
0.410 hours
Interval 0.25 to 0.5

Adverse Events

Ketorolac Tromethamine

Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths

Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)

Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths

Ketorolac Tromethamine With 5% Lidocaine HCl

Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths

Ketorolac Tromethamine With 6% Lidocaine HCl

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Ketorolac Tromethamine
n=16 participants at risk
Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)
n=16 participants at risk
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Ketorolac Tromethamine With 5% Lidocaine HCl
n=16 participants at risk
Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
Ketorolac Tromethamine With 6% Lidocaine HCl
n=16 participants at risk
30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
Vascular disorders
Hematoma
0.00%
0/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
Vascular disorders
Hot flush
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
Respiratory, thoracic and mediastinal disorders
Nasal oedema
56.2%
9/16 • 1 month and 2 weeks
18.8%
3/16 • 1 month and 2 weeks
37.5%
6/16 • 1 month and 2 weeks
18.8%
3/16 • 1 month and 2 weeks
Respiratory, thoracic and mediastinal disorders
Nasal septum ulceration
6.2%
1/16 • 1 month and 2 weeks
12.5%
2/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
General disorders
Fatigue
0.00%
0/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
Infections and infestations
Nasopharyngitis
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
Infections and infestations
Rhinitis
0.00%
0/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
Nervous system disorders
Headache
6.2%
1/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
Psychiatric disorders
Nervousness
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
Reproductive system and breast disorders
Dysmenorrhea
0.00%
0/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
0.00%
0/16 • 1 month and 2 weeks
Respiratory, thoracic and mediastinal disorders
Epistaxis
12.5%
2/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
6.2%
1/16 • 1 month and 2 weeks
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
37.5%
6/16 • 1 month and 2 weeks
37.5%
6/16 • 1 month and 2 weeks
37.5%
6/16 • 1 month and 2 weeks
37.5%
6/16 • 1 month and 2 weeks

Additional Information

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

Luitpold Pharmaceuticals, Inc.

Phone: 610-650-4200

Results disclosure agreements

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