Safety and Pharmacokinetics Study of Intranasal Ketorolac in Elderly and Nonelderly Adult Healthy Subjects

• Sponsor: American Regent, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01365624
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 5
• Patients Per Site Per Month: 6

Study Details

Study Description

Brief Summary

This study had an open-label, single-dose design. All subjects received a single dose of 30 mg of intranasal ketorolac. Blood samples for determination of ketorolac plasma levels were obtained pre-dose and at specified time points over 24 hours post-dose.

The primary objective of this trial was to compare the pharmacokinetics of intranasal ketorolac between elderly and nonelderly adult subjects. The secondary objective was to evaluate the safety profile of intranasal ketorolac in elderly subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: Ketorolac tromethamine	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Safety and Pharmacokinetics Study of Intranasal Ketorolac in Elderly and Nonelderly Adult Healthy Subjects
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketorolac tromethamine	Drug: Ketorolac tromethamine; Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Plasma Concentration) [Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose]

2. Tmax (Time to Reach Maximum Plasma Concentration) [Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose]

3. AUClast (Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Time Point Post-dose [Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose]

4. AUC (Area Under the Plasma Concentration-time Profile From Time 0 to Infinity [Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose]

5. t1/2z (Terminal Half-life) [Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose]

6. MRT (Mean Residence Time) [Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• The elderly population consisted of male or female volunteers aged > of = 65 years

• The nonelderly adult population consisted of male or female volunteers aged < 65 years

• Generally good health in the opinion of the Investigator, as determined by a prestudy physical examination with no clinically significant abnormalities for age, vital signs within normal ranges or outside normal range but not deemed clinically significant for age in the opinion of the Investigator, and no clinically significant electrocardiogram (ECG) abnormalities for age

• Bilaterally patent nasal airways at screening as assessed by the Investigator

• Body mass index (BMI) 15-30 kg/m2

• Female subjects of childbearing potential must consent to use a medically acceptable method of contraception (oral or implanted contraceptive hormones, condom or diaphragm with spermicidal agent, intrauterine device, or surgical sterilization) throughout the study period

• Ability to provide written informed consent

• Prestudy clinical laboratory findings within normal ranges or if outside normal range not deemed clinically significant for age in the opinion of the Investigator

Exclusion Criteria:

• Allergy or sensitivity to ketorolac or formulation ingredients

• History of co-existing nasal polyps, NSAID sensitivity, and asthma

• Allergic reaction to aspirin or other NSAIDs

• Current upper respiratory tract infection or other respiratory tract condition that could interfere with the absorption of the nasal spray or with the assessment of AEs

• Use of any prescribed or over-the-counter (OTC) drug in the 72 h prior to entry into the study with the exception of occasional acetaminophen up to 24 h prior to entry

• Suspicion of rhinitis medicamentosa (chronic daily use of topical decongestants)

• Use of a monoamine oxidase (MAO) inhibitor in the 14 days prior to study entry

• Positive serum test for human immunodeficiency virus (HIV) or hepatitis B or C

• Positive alcohol breath test at screening or on entry into the study

• Positive urine screen for any nonprescribed drug of abuse at screening or on entry into the study

• History of cocaine use

• Blood donation within 30 days of beginning study participation

• Active peptic ulcer disease or a history of peptic ulcer disease or gastrointestinal bleeding

• Serum creatinine > 2.0 mg/dL

• Current tobacco use or a past history of smoking within 5 years of study entry

• Any other clinically significant medical problem, which in the opinion of the Investigator would interfere with study participation

• Participation within 30 days of study entry or within 5 times the half-life, whichever is longer, in another investigational drug study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seaview Research	Miami	Florida	United States	33126

Sponsors and Collaborators

• American Regent, Inc.

Investigators

• Study Chair: Lincoln Bynum, MD, ICON Developmental Solutions

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: American Regent, Inc.
• ClinicalTrials.gov Identifier: NCT01365624
• Other Study ID Numbers: ROX 2007-02
• First Posted: Jun 3, 2011
• Last Update Posted: Feb 6, 2013
• Last Verified: Jan 1, 2013

• Additional relevant MeSH terms: Ketorolac; Ketorolac Tromethamine

Study Results

Participant Flow

Recruitment Details	February 2008 through April 2008; Clinical Unit
Pre-assignment Detail	After subjects had given their informed consent, subjects were required to pass a screening visit within 3 weeks prior to study drug administration.

Arm/Group Title	Ketorolac Tromethamine (Elderly Adults ≥ 65)	Ketorolac Tromethamine (Nonelderly Adults < 65)
Arm/Group Description	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)
Period Title: Overall Study
STARTED	15	15
COMPLETED	15	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ketorolac Tromethamine (Elderly Adults ≥ 65)	Ketorolac Tromethamine (Nonelderly Adults < 65)	Total
Arm/Group Description	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)	Total of all reporting groups
Overall Participants	15	15	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	15 100%	15 50%
>=65 years	15 100%	0 0%	15 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.9 (5.9)	44.2 (10.3)	58.1 (16.3)
Sex: Female, Male (Count of Participants)
Female	8 53.3%	6 40%	14 46.7%
Male	7 46.7%	9 60%	16 53.3%
Region of Enrollment (participants) [Number]
United States	15 100%	15 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Cmax (Maximum Plasma Concentration)
Time Frame	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketorolac Tromethamine (Elderly Adults ≥ 65)	Ketorolac Tromethamine (Nonelderly Adults < 65)
Arm/Group Description	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)
Measure Participants	15	15
Mean (Standard Deviation) [ng/mL]	1782.286 (1184.843)	1840.111 (995.930)

2. Primary Outcome

Title	Tmax (Time to Reach Maximum Plasma Concentration)
Time Frame	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketorolac Tromethamine (Elderly Adults ≥ 65)	Ketorolac Tromethamine (Nonelderly Adults < 65)
Arm/Group Description	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)
Measure Participants	15	15
Median (Full Range) [hours]	0.750	0.750

3. Primary Outcome

Title	AUClast (Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Time Point Post-dose
Time Frame	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketorolac Tromethamine (Elderly Adults ≥ 65)	Ketorolac Tromethamine (Nonelderly Adults < 65)
Arm/Group Description	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)
Measure Participants	15	15
Mean (Standard Deviation) [ng*hours/mL]	7323.5 (4633.1)	6536.5 (3361.8)

4. Primary Outcome

Title	AUC (Area Under the Plasma Concentration-time Profile From Time 0 to Infinity
Time Frame	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Two subjects had abnormally low plasma ketorolac concentration-time profiles that were inconsistent with the rest of the elderly population.

Arm/Group Title	Ketorolac Tromethamine (Elderly Adults ≥ 65)	Ketorolac Tromethamine (Nonelderly Adults < 65)
Arm/Group Description	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)
Measure Participants	13	15
Mean (Standard Deviation) [ng*hours/mL]	8794.8 (4129.4)	6890.8 (3448.5)

5. Primary Outcome

Title	t1/2z (Terminal Half-life)
Time Frame	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Two subjects had abnormally low plasma ketorolac concentration-time profiles that were inconsistent with the rest of the elderly population.

Arm/Group Title	Ketorolac Tromethamine (Elderly Adults ≥ 65)	Ketorolac Tromethamine (Nonelderly Adults < 65)
Arm/Group Description	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)
Measure Participants	13	15
Mean (Standard Deviation) [hours]	4.521 (1.142)	3.313 (0.961)

6. Primary Outcome

Title	MRT (Mean Residence Time)
Time Frame	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Two subjects had abnormally low plasma ketorolac concentration-time profiles that were inconsistent with the rest of the elderly population.

Arm/Group Title	Ketorolac Tromethamine (Elderly Adults ≥ 65)	Ketorolac Tromethamine (Nonelderly Adults < 65)
Arm/Group Description	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)
Measure Participants	13	15
Mean (Standard Deviation) [hours]	6.024 (1.496)	4.441 (1.060)

Adverse Events

Time Frame	1 month and 1 week
Arm/Group Title	Ketorolac Tromethamine (Elderly Adults ≥ 65)		Ketorolac Tromethamine (Nonelderly Adults < 65)
Arm/Group Description	Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)		Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)
All Cause Mortality
	Ketorolac Tromethamine (Elderly Adults ≥ 65)		Ketorolac Tromethamine (Nonelderly Adults < 65)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ketorolac Tromethamine (Elderly Adults ≥ 65)		Ketorolac Tromethamine (Nonelderly Adults < 65)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Ketorolac Tromethamine (Elderly Adults ≥ 65)		Ketorolac Tromethamine (Nonelderly Adults < 65)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/15 (6.7%)		1/15 (6.7%)
Infections and infestations
Hordeolum	1/15 (6.7%)	1	0/15 (0%)	0
Nervous system disorders
Headache	0/15 (0%)	0	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

More Information

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.