Tolerability, Safety and Pharmacokinetics of Four Formulations of Ketorolac Tromethamine in Healthy Volunteers
Condition: Healthy Volunteers
Intervention: Ketorolac Tromethamine; Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl); Ketorolac Tromethamine with 5% Lidocaine HCl; 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl
Intervention description: 30 mg Ketorolac Tromethamine intranasal (IN); 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN; 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN; 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Intervention MeSH terms: Ketorolac; Ketorolac Tromethamine; Lidocaine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility 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 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