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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Ketorolac tromethamine; Drug: Ketorolac tromethamine

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom
    • ICON Developmental Solutions

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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; 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
Experimental: Ketorolac tromethamine (Part B)	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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Egalet Ltd
• Investigators: Principal Investigator: Cyril Clarke, BSc, MB BS, MFPM, ICON Developmental Solutions

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: May 27, 2011
• First Submitted That Met QC Criteria: May 27, 2011
• First Posted (Estimate): June 1, 2011

Study Record Updates

• Last Update Posted (Actual): March 6, 2018
• Last Update Submitted That Met QC Criteria: March 2, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: ROX 2006-01