Study of the Tolerability of Ketorolac Tromethamine Following Intranasal Administration in Healthy Volunteers
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ketorolac tromethamine (Part A)
|
Drug: Ketorolac tromethamine
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
|
| Experimental: Ketorolac tromethamine (Part B)
|
Drug: Ketorolac tromethamine
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
|
Outcome Measures
Primary Outcome Measures
- Discomfort Measurement on a Visual Analogue Scale [15 minutes post-dose]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female volunteers, aged 18 to 60 years inclusive
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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
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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
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Subject had given signed informed consent
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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.
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Subject's medical history was considered normal, with no clinically significant abnormalities
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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
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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
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Subject had bilateral patent nasal airways at screening and Day 1 as assessed by the Investigator
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Body weight of at least 60 kg
Exclusion Criteria:
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Subject had had a clinically significant illness in the four weeks before screening
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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
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Subject had a significant history of drug/solvent abuse, or a positive drugs of abuse test at screening
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Subject had a history of alcohol abuse or currently drank in excess of 28 units per week (males) or 21 units per week (females)
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Current tobacco use or a history of smoking within the past five years
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Subject was in the opinion of the Investigator not suitable to participate in the study
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Subject had participated in any clinical study with an investigational drug/device within three months prior to dosing
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Subject had a positive result of human immunodeficiency virus (HIV) screen, Hepatitis B screen or Hepatitis C screen
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Subject had had a serious adverse reaction or significant hypersensitivity to any drug
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Subject had donated 500 mL or more of blood within the three months prior to screening
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Any history of co-existing nasal polyps, NSAID sensitivity and asthma
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Allergic reaction to aspirin or other NSAIDs
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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)
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Any suspicion of rhinitis medicamentosa (chronic daily use of topical decongestants)
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Use of a monoamine oxidase inhibitor in the 14 days prior to study entry
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Active peptic ulcer disease, gastrointestinal bleeding or perforation, or a history of peptic ulcer disease or gastrointestinal bleeding
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Anemia due to unexplained or known gastrointestinal bleeding
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History of asthma or any other chronic pulmonary disorder
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Renal impairment or a risk of renal failure due to volume depletion
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Known sensitivity to lidocaine hydrochloride
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Previous history of nasal surgery
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ICON Developmental Solutions | Manchester | United Kingdom |
Sponsors and Collaborators
- Egalet Ltd
Investigators
- Principal Investigator: Cyril Clarke, BSc, MB BS, MFPM, ICON Developmental Solutions
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ROX 2006-01