Study to Assess the PK of Ketorolac Tromethamine Intranasal and to Assess the Effects of a Oxymetazoline Hydrochloride on the PK of Ketorolac Tromethamine

NCT01363089 | Completed Phase 1 DMC

• 1 other identifier: ROX 2006-03
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This was an open label, two way crossover study in healthy male subjects. Two treatments were administered to each subject, one treatment per study period, in a randomized manner. Subjects remained resident in the Clinical Unit from the evening of Day 1 until the morning of Day 2 of each period and there was a washout period of at least 2 days between treatments. A post study medical examination was performed prior to discharge in Period 2. The objective of this study was to assess the effects of a single dose of intranasal oxymetazoline hydrochloride on the pharmacokinetics of intranasal ketorolac in healthy male subjects.

Conditions

Assess Pharmacokinetics of Ketorolac Tromethamine Intranasal and Assess Effects of a Oxymetazoline Hydrochloride on the PK of Ketorolac Tromethamine

Outcome Measures

Primary Outcomes (6)

• Cmax (the maximum observed plasma concentration)

  Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

  All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

• Tmax (the time to maximum concentration)

  Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

  All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

• AUC 0-t (the area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable time point post-dose

  Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

  All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

• AUCinf (the AUC from time zero to infinity, where possible

  Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

  All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

• t1/2z (the terminal half-life, where possible

  Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

  All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

• MRT (the mean residence time)

  Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

  All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

Study Arms (2)

Ketorolac tromethamine

EXPERIMENTAL

Drug: Ketorolac tromethamine

Oxymetazoline hydrochloride

EXPERIMENTAL

Drug: Oxymetazoline hydrochloride

Interventions

Ketorolac tromethamine DRUG

30 mg of intranasal ketorolac tromethamine (one 100 µL spray into each nostril of a 15%, pH 7.2 solution)

Ketorolac tromethamine

Oxymetazoline hydrochloride DRUG

Single intranasal dose of oxymetazoline hydrochloride (Afrazine®) (3 sprays of a 0.05% solution into each nostril) followed 30 minutes later by 30 mg of intranasal ketorolac tromethamine (one 100 µL spray into each nostril of a 15%, pH 7.2 solution)

Oxymetazoline hydrochloride

Eligibility Criteria

• Age: 18 Years - 62 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject was male and aged 18 to 62 years inclusive
• 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, intrauterine device or surgical sterilization plus condom or diaphragm with spermicidal agent) throughout the study period
• Subject had given signed informed consent
• Subject was within 20% of normal weight for his 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 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
• Subject had a body weight of at least 60 kg

You may not qualify if:

• Subject had had a clinically significant illness in the 4 weeks before screening
• Subject used 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 (h) prior to dosing. Use of multivitamins was 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
• Subject currently used tobacco or had a history of smoking within the past 5 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 3 months prior to dosing
• Subject had a positive human immunodeficiency virus (HIV), hepatitis B 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 3 months prior to screening
• Subject had any history of co-existing nasal polyps, NSAID sensitivity and asthma
• Subject had an allergic reaction to aspirin or other NSAIDs
• Subject currently had an upper respiratory tract infection or other respiratory tract condition that could interfere with the absorption of the nasal spray or with the assessment of AEs
• Subject had any suspicion of rhinitis medicamentosa (chronic daily use of topical decongestants)
• Subject had used a monoamine oxidase inhibitor in the 14 days prior to study entry

Sponsors & Collaborators

• Egalet Ltd: lead

Study Sites (1)

ICON Development Solutions

Manchester, United Kingdom

Location

MeSH Terms

Interventions

Ketorolac Tromethamine; Oxymetazoline

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Cyril Clarke, BSc MB BS MFPM

  ICON Development Solutions

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2011
• First Posted: June 1, 2011
• Study Start: January 1, 2007
• Primary Completion: March 1, 2007
• Study Completion: February 1, 2008
• Last Updated: February 9, 2017

Record last verified: 2017-02

Locations

GB (1)