Healthy Subjects
Conditions
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.
Interventions
DRUGKetorolac tromethamine
Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)
Sponsors
American Regent, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
United States
Participant flow
Recruitment details
February 2008 through April 2008; Clinical Unit
Pre-assignment details
After subjects had given their informed consent, subjects were required to pass a screening visit within 3 weeks prior to study drug administration.
Participants by arm
| Arm | Count |
|---|---|
| Ketorolac Tromethamine (Elderly Adults ≥ 65) Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril) | 15 |
| Ketorolac Tromethamine (Nonelderly Adults < 65) Ketorolac tromethamine : Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril) | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Ketorolac Tromethamine (Nonelderly Adults < 65) | Ketorolac Tromethamine (Elderly Adults ≥ 65) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 15 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 0 Participants | 15 Participants |
| Age Continuous | 44.2 years STANDARD_DEVIATION 10.3 | 71.9 years STANDARD_DEVIATION 5.9 | 58.1 years STANDARD_DEVIATION 16.3 |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 14 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
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
Population: Two subjects had abnormally low plasma ketorolac concentration-time profiles that were inconsistent with the rest of the elderly population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Tromethamine (Elderly Adults ≥ 65) | AUC (Area Under the Plasma Concentration-time Profile From Time 0 to Infinity | 8794.8 ng*hours/mL | Standard Deviation 4129.4 |
| Ketorolac Tromethamine (Nonelderly Adults < 65) | AUC (Area Under the Plasma Concentration-time Profile From Time 0 to Infinity | 6890.8 ng*hours/mL | Standard Deviation 3448.5 |
Primary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Tromethamine (Elderly Adults ≥ 65) | AUClast (Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Time Point Post-dose | 7323.5 ng*hours/mL | Standard Deviation 4633.1 |
| Ketorolac Tromethamine (Nonelderly Adults < 65) | AUClast (Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Time Point Post-dose | 6536.5 ng*hours/mL | Standard Deviation 3361.8 |
Primary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Tromethamine (Elderly Adults ≥ 65) | Cmax (Maximum Plasma Concentration) | 1782.286 ng/mL | Standard Deviation 1184.843 |
| Ketorolac Tromethamine (Nonelderly Adults < 65) | Cmax (Maximum Plasma Concentration) | 1840.111 ng/mL | Standard Deviation 995.93 |
Primary
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
Population: Two subjects had abnormally low plasma ketorolac concentration-time profiles that were inconsistent with the rest of the elderly population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Tromethamine (Elderly Adults ≥ 65) | MRT (Mean Residence Time) | 6.024 hours | Standard Deviation 1.496 |
| Ketorolac Tromethamine (Nonelderly Adults < 65) | MRT (Mean Residence Time) | 4.441 hours | Standard Deviation 1.06 |
Primary
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
Population: Two subjects had abnormally low plasma ketorolac concentration-time profiles that were inconsistent with the rest of the elderly population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Tromethamine (Elderly Adults ≥ 65) | t1/2z (Terminal Half-life) | 4.521 hours | Standard Deviation 1.142 |
| Ketorolac Tromethamine (Nonelderly Adults < 65) | t1/2z (Terminal Half-life) | 3.313 hours | Standard Deviation 0.961 |
Primary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketorolac Tromethamine (Elderly Adults ≥ 65) | Tmax (Time to Reach Maximum Plasma Concentration) | 0.750 hours |
| Ketorolac Tromethamine (Nonelderly Adults < 65) | Tmax (Time to Reach Maximum Plasma Concentration) | 0.750 hours |