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

• Status: Completed
• Trial end date: 2007-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Egalet Ltd; Luitpold Pharmaceuticals
• Treatments: Ketorolac; Ketorolac Tromethamine; Lidocaine

Criteria

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