Study to Determine the Tolerability, Safety and Pharmacokinetics of Ketorolac Tromethamine by Intranasal Administration in Healthy Volunteers
Condition: Healthy Volunteers
Intervention: Ketorolac tromethamine
Intervention description: Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.
Intervention MeSH terms: Ketorolac; Ketorolac Tromethamine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This was a phase 1, open label, multiple dose study in healthy male and female volunteers.
      Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for
      three days (seven doses in total). Doses were administered every eight hours.

      The objective of this study in healthy volunteers was to determine the safety, tolerability,
      and pharmacokinetics of multiple doses of intranasal ketorolac tromethamine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female volunteers, aged 18 to 60 years inclusive

          -  Female subjects of child bearing potential were to have 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 using 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 ranges 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 of at least 60 kg

        Exclusion Criteria:

          -  Subject had a clinically significant illness in the four weeks prior to 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. 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

          -  Subjects with a history of alcohol abuse or those currently drinking more than 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

          -  Subjects who had participated in any clinical study with an investigational
             drug/device within three 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 who had a serious adverse reaction or significant hypersensitivity to any
             drug

          -  Subjects having 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
             may 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 (MAOI) 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