Study of the Tolerability of Ketorolac Tromethamine Following Intranasal Administration in Healthy Volunteers

Study Overview
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Brief Summary
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This was a Phase 1, double blind, two part study in healthy male and female volunteers. Each subject participated in only one part of the study. In Part A subjects received one dose of 15 mg ketorolac tromethamine with a lidocaine hydrochloride free formulation in one nostril and one dose of 15 mg ketorolac tromethamine containing 6% lidocaine hydrochloride in the other nostril, in a randomized manner. In Part B subjects were randomized to receive a single intranasal dose of 15 mg ketorolac tromethamine containing 0% lidocaine hydrochloride into one nostril and either placebo or a single intranasal dose of 15 mg ketorolac tromethamine containing 0%, 4% or 6% lidocaine hydrochloride into the other nostril. During the study, subjects remained resident from the morning of Day 1 until the afternoon of Day 1, when a post-study medical was performed prior to discharge. The objective of this study was to compare the tolerability of formulations of ketorolac tromethamine with differing concentrations of lidocaine hydrochloride (0% and 6% in Part A and 0%, 4%, 6% and placebo in Part B) following intranasal administration to healthy volunteers.

Official Title
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A Phase 1, Double-Blind, Study of the Tolerability of Formulations of Ketorolac Tromethamine Following Intranasal Administration in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Ketorolac tromethamine
* Drug: Ketorolac tromethamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female volunteers, aged 18 to 60 years inclusive Female subjects of child bearing potential must have had a negative urine pregnancy test prior to entry into the study and must not have been breast feeding All female subjects of child bearing potential and all male subjects with female partners of child bearing potential must have consented 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 Subject had given signed informed consent Subject was within 20% of normal weight for his/her height and body build according to the table of Desirable Weights for Men and Women (Metropolitan Life Insurance Co. 1999) Subject's medical history was considered normal, with no clinically significant abnormalities Subject was considered to be in good health in the opinion of the Investigator, as determined by a pre-study physical examination with no clinically significant abnormalities, vital signs within normal ranges and an electrocardiogram (ECG) with no clinically significant abnormalities Subject's pre-study clinical laboratory findings were within the normal range or if outside of the normal range were not deemed clinically significant in the opinion of the Investigator Subject had bilateral patent nasal airways at screening and Day 1 as assessed by the Investigator Body weight of at least 60 kg Exclusion Criteria: Subject had had a clinically significant illness in the four weeks before screening Use of prescribed medications in the three weeks prior to dosing or over-the-counter preparations for seven days prior to dosing, except paracetamol which was allowed up to 48 hours prior to dosing. However, use of multivitamins and oral contraceptives were permitted Subject had a significant history of drug/solvent abuse, or a positive drugs of abuse test at screening Subject had a history of alcohol abuse or currently drank in excess of 28 units per week (males) or 21 units per week (females) Current tobacco use or a history of smoking within the past five years Subject was in the opinion of the Investigator not suitable to participate in the study Subject had participated in any clinical study with an investigational drug/device within three months prior to dosing Subject had a positive result of human immunodeficiency virus (HIV) screen, Hepatitis B screen or Hepatitis C screen Subject had had a serious adverse reaction or significant hypersensitivity to any drug Subject had donated 500 mL or more of blood within the three months prior to screening Any 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 have interfered with the absorption of the nasal spray or with the assessment of adverse events (AEs) Any suspicion of rhinitis medicamentosa (chronic daily use of topical decongestants) Use of a monoamine oxidase inhibitor in the 14 days prior to study entry Active peptic ulcer disease, gastrointestinal bleeding or perforation, or a history of peptic ulcer disease or gastrointestinal bleeding Anemia due to unexplained or known gastrointestinal bleeding History of asthma or any other chronic pulmonary disorder Renal impairment or a risk of renal failure due to volume depletion Known sensitivity to lidocaine hydrochloride Previous history of nasal surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketorolac tromethamine (Part A)<br> | Drug: Ketorolac tromethamine<br>* One dose of 15 mg ketorolac tromethamine with a lidocaine hydrochloride free formulation in one nostril and one dose of 15 mg ketorolac tromethamine containing 6% lidocaine hydrochloride in the other nostril<br>|
| Experimental: Ketorolac tromethamine (Part B)<br> | Drug: Ketorolac tromethamine<br>* One dose of 15 mg ketorolac tromethamine containing 0% lidocaine hydrochloride into one nostril and either placebo or a single intranasal dose of 15 mg Ketorolac tromethamine containing 0%, 4% or 6% lidocaine hydrochloride into the other nostril<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Discomfort Measurement on a Visual Analogue Scale | Following administration of each treatment, subjects completed a visual analogue scale (VAS) (ranging from no discomfort to severe discomfort) at 1, 5, 10 and 15 minutes post-dose. If after the 15 minute VAS assessment discomfort was still present the subject was asked to complete further VAS assessments, at 5 minute intervals, until the discomfort had dissipated. | 15 minutes post-dose |