Tolerability, Safety and Pharmacokinetics of Four Formulations of Ketorolac Tromethamine in Healthy Volunteers

Phase 1

Completed

Conditions: Healthy Volunteers

Interventions: Drug: Ketorolac Tromethamine with 5% Lidocaine HCl
Drug: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl)
Drug: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl
Drug: Ketorolac Tromethamine

Registration Number: NCT01355588

Lead Sponsor: Egalet Ltd

Brief Summary: This was a phase 1, double-blind, 4-way crossover study in healthy male and female volunteers. Subjects received 4 formulations of intranasal ketorolac tromethamine 30 mg. There was a wash-out period of 3-7 days between each dose. On Day 1 of each period subjects were randomised to receive either a single intranasal dose of 30 mg ketorolac tromethamine alone or single intranasal dose of 30 mg ketorolac tromethamine with 4%, 5% or 6% lidocaine hydrochloride. At the end of the study each subject had received all 4 treatments.

The primary objective of this study in healthy volunteers was to compare the safety, tolerability, and pharmacokinetics of 4 formulations of ketorolac tromethamine. A secondary objective was to monitor lidocaine hydrochloride plasma levels.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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 sterilisation) 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 range and an ECG with no clinically significant abnormalities
Subject's pre-study clinical laboratory findings were within normal range or, if outside of the normal range, not deemed clinically significant in the opinion of the Investigator
Subject had bilateral patent nasal airways at screening as assessed by the Investigator
Body weight was at least 70 kg

Exclusion Criteria

Subject had a clinically significant illness in the 4 weeks before screening
Use of prescribed medications in the 3 weeks prior to dosing or over-the-counter preparations for 7 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 history of alcohol abuse or 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 5 years
Subject was, in the opinion of the Investigator, not suitable to participate in the study
Subjects who had participated in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing
Subjects who had a positive result of HIV screen, Hepatitis B screen or Hepatitis C screen
Subjects with a serious adverse reaction or significant hypersensitivity to any drug
Subjects who has donated 500 mL or more of blood within the 3 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 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ketorolac Tromethamine with 5% Lidocaine HCl	Ketorolac Tromethamine with 5% Lidocaine HCl	-
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl)	Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl)	-
Ketorolac Tromethamine with 6% Lidocaine HCl	30 mg Ketorolac Tromethamine with 6% Lidocaine HCl	-
Ketorolac Tromethamine	Ketorolac Tromethamine	-

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax)	Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose
Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Post-dose (AUC 0-t)	Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose
Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUC 0-∞)	Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Secondary Outcome Measures

Name	Time	Method
Time to Reach Maximum Plasma Concentration (Tmax)	Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose