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

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ClinicalTrials.gov Identifier: NCT01355588
Recruitment Status : Completed
First Posted : May 18, 2011
Results First Posted : May 3, 2013
Last Update Posted : March 16, 2017
Sponsor:
Information provided by (Responsible Party):
Egalet Ltd

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Healthy Volunteers
Interventions Drug: Ketorolac Tromethamine
Drug: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl)
Drug: Ketorolac Tromethamine with 5% Lidocaine HCl
Drug: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl
Enrollment 16
Recruitment Details 1 month and 2 weeks; Medeval Limited Skelton House, Manchester Science Park, Lloyd Street North, Manchester M15 6SH, U.K.
Pre-assignment Details  
Arm/Group Title Treatment A, Treatment C, Treatment D, Treatment B Treatment B, Treatment D, Treatment C, Treatment A Treatment C, Treatment B, Treatment A, Treatment D Treatment D, Treatment A, Treatment B, Treatment C
Hide Arm/Group Description 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: 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: 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: 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
Period Title: First Intervention (Day 1)
Started 4 4 4 4
Completed 4 4 4 4
Not Completed 0 0 0 0
Period Title: Washout (3-7 Days)
Started 4 4 4 4
Completed 4 4 4 4
Not Completed 0 0 0 0
Period Title: Second Intervention (After Washout)
Started 4 4 4 4
Completed 4 4 4 4
Not Completed 0 0 0 0
Period Title: Washout (3-7 Days)
Started 4 4 4 4
Completed 4 4 4 4
Not Completed 0 0 0 0
Period Title: Third Intervention (After Washout)
Started 4 4 4 4
Completed 4 4 4 4
Not Completed 0 0 0 0
Period Title: Washout (3-7 Days)
Started 4 4 4 4
Completed 4 4 4 4
Not Completed 0 0 0 0
Period Title: Fourth Intervention (After Washout)
Started 4 4 4 4
Completed 4 4 4 4
Not Completed 0 0 0 0
Arm/Group Title Treatment A, Treatment C, Treatment D, Treatment B Treatment B, Treatment D, Treatment C, Treatment A Treatment C, Treatment B, Treatment A, Treatment D Treatment D, Treatment A, Treatment B, Treatment C Total
Hide Arm/Group Description 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: 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: 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: 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 of all reporting groups
Overall Number of Baseline Participants 4 4 4 4 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 4 participants 16 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
 100.0%
4
 100.0%
4
 100.0%
4
 100.0%
16
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 4 participants 4 participants 4 participants 16 participants
34.25  (17.21) 40.75  (19.97) 34.0  (15.90) 50.25  (10.31) 39.8  (16.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 4 participants 16 participants
Female
2
  50.0%
0
   0.0%
1
  25.0%
2
  50.0%
5
  31.3%
Male
2
  50.0%
4
 100.0%
3
  75.0%
2
  50.0%
11
  68.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United Kingdom Number Analyzed 4 participants 4 participants 4 participants 4 participants 16 participants
4 4 4 4 16
1.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Hide Description [Not Specified]
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Tromethamine Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl) Ketorolac Tromethamine With 5% Lidocaine HCl Ketorolac Tromethamine With 6% Lidocaine HCl
Hide Arm/Group Description:
Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Overall Number of Participants Analyzed 16 16 16 16
Mean (Standard Deviation)
Unit of Measure: ng/mL
2059.6  (801.7) 1963.1  (1020.8) 1799.9  (714.1) 2048.5  (817.6)
2.Primary Outcome
Title Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Post-dose (AUC 0-t)
Hide Description [Not Specified]
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Tromethamine Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl) Ketorolac Tromethamine With 5% Lidocaine HCl Ketorolac Tromethamine With 6% Lidocaine HCl
Hide Arm/Group Description:
Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Overall Number of Participants Analyzed 16 16 16 16
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
8440.6  (4021.2) 7856.0  (4211.8) 7561.5  (4051.2) 8103.8  (3786.3)
3.Primary Outcome
Title Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUC 0-∞)
Hide Description [Not Specified]
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Tromethamine Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl) Ketorolac Tromethamine With 5% Lidocaine HCl Ketorolac Tromethamine With 6% Lidocaine HCl
Hide Arm/Group Description:
Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Overall Number of Participants Analyzed 16 16 16 16
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
9061.9  (4526.8) 8694.5  (4477.1) 8086.8  (4608.2) 8677.6  (4301.0)
4.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax)
Hide Description [Not Specified]
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Tromethamine Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl) Ketorolac Tromethamine With 5% Lidocaine HCl Ketorolac Tromethamine With 6% Lidocaine HCl
Hide Arm/Group Description:
Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Overall Number of Participants Analyzed 16 16 16 16
Median (Full Range)
Unit of Measure: hours
0.510
(0.50 to 1.50)
0.500
(0.25 to 4.00)
0.390
(0.25 to 0.75)
0.410
(0.25 to 0.50)
Time Frame 1 month and 2 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ketorolac Tromethamine Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl) Ketorolac Tromethamine With 5% Lidocaine HCl Ketorolac Tromethamine With 6% Lidocaine HCl
Hide Arm/Group Description Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN) Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
All-Cause Mortality
Ketorolac Tromethamine Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl) Ketorolac Tromethamine With 5% Lidocaine HCl Ketorolac Tromethamine With 6% Lidocaine HCl
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ketorolac Tromethamine Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl) Ketorolac Tromethamine With 5% Lidocaine HCl Ketorolac Tromethamine With 6% Lidocaine HCl
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/16 (0.00%)   0/16 (0.00%)   0/16 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ketorolac Tromethamine Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl) Ketorolac Tromethamine With 5% Lidocaine HCl Ketorolac Tromethamine With 6% Lidocaine HCl
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/16 (68.75%)   9/16 (56.25%)   9/16 (56.25%)   8/16 (50.00%) 
General disorders         
Fatigue * 1  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%) 
Infections and infestations         
Nasopharyngitis * 1  1/16 (6.25%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%) 
Rhinitis * 1  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%) 
Musculoskeletal and connective tissue disorders         
Musculoskeletal chest pain * 1  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%) 
Nervous system disorders         
Headache * 1  1/16 (6.25%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%) 
Psychiatric disorders         
Nervousness * 1  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%) 
Reproductive system and breast disorders         
Dysmenorrhea * 1  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Epistaxis * 1  2/16 (12.50%)  1/16 (6.25%)  1/16 (6.25%)  1/16 (6.25%) 
Nasal discomfort * 1  6/16 (37.50%)  6/16 (37.50%)  6/16 (37.50%)  6/16 (37.50%) 
Nasal oedema * 1  9/16 (56.25%)  3/16 (18.75%)  6/16 (37.50%)  3/16 (18.75%) 
Nasal septum ulceration * 1  1/16 (6.25%)  2/16 (12.50%)  0/16 (0.00%)  0/16 (0.00%) 
Pharyngolaryngeal pain * 1  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Rhinorrhea * 1  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%) 
Vascular disorders         
Hematoma * 1  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%) 
Hot flush * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 8.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: David Bregman, M.D., Ph.D.
Organization: Luitpold Pharmaceuticals, Inc.
Phone: 610-650-4200 ext 828
Responsible Party: Egalet Ltd
ClinicalTrials.gov Identifier: NCT01355588     History of Changes
Other Study ID Numbers: ROX 2005-02
First Submitted: May 16, 2011
First Posted: May 18, 2011
Results First Submitted: November 16, 2012
Results First Posted: May 3, 2013
Last Update Posted: March 16, 2017