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

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Other
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: February 2007

Interventions

  • 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
  • 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

Arms, Groups and Cohorts

  • Experimental: Ketorolac tromethamine (Part A)
  • Experimental: Ketorolac tromethamine (Part B)

Clinical Trial Outcome Measures

Primary Measures

  • Discomfort Measurement on a Visual Analogue Scale
    • Time Frame: 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Egalet Ltd
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Cyril Clarke, BSc, MB BS, MFPM, Principal Investigator, ICON Developmental Solutions

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