Study to Assess the Absorption and Tolerability of Intranasal Ketorolac Tromethamine and to Assess the Effects of Oxymetazoline Hydrochloride and Fluticasone Propionate on the Absorption and Tolerability of Intranasal Ketorolac Tromethamine in Participants With Allergic Rhinitis

NCT01365650 | Completed Phase 1 Results

• 1 other identifier: ROX 2007-03
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This was an open label, three way study in participants with symptomatic allergic rhinitis. The following 3 treatments were administered to each subject during dosing periods 1, 2 and 3, respectively:

• Treatment A: Single intranasal dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on Day 1 of Period 1.
• Treatment B: Single intranasal dose of oxymetazoline hydrochloride followed by a single intranasal dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) 30 minutes later on Day 1 of Period 2.
• Treatment C: Seven days of treatment with intranasal fluticasone propionate (between Periods 2 and 3) followed by a single intranasal dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on Day 1 of Period 3. Subjects remained resident in the Clinical Unit from Day 1 until the morning of Day 2 in each period and there was a washout period of 2 to 7 days between periods. A post study medical was performed within 7 days of Period 3. The objectives of this study were:
• To assess the pharmacokinetics (PK) of intranasal ketorolac in participants with symptomatic allergic rhinitis.
• To assess the effects of a single dose of intranasal oxymetazoline hydrochloride on the pharmacokinetics and tolerability of intranasal ketorolac in participants with symptomatic allergic rhinitis.
• To assess the effects of chronic administration of fluticasone propionate on the bioavailability and tolerability of intranasal ketorolac in participants with symptomatic allergic rhinitis.

Conditions

Allergic Rhinitis

Outcome Measures

Primary Outcomes (6)

• Cmax (the Maximum Observed Plasma Concentration)

  PK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.

  Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethamine

• Tmax (the Time to Maximum Concentration)

  PK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.

  Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethamine

• AUC 0-t (the Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Time Point Post-dose)

  PK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.

  Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethamine

• AUC 0-∞ (the AUC From Time Zero to Infinity, Where Possible)

  PK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.

  Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethamine

• t1/2z (the Terminal Half-life, Where Possible)

  PK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.

  Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethamine

• MRT (the Mean Residence Time)

  PK analysis by standard model was performed by a pharmacokineticist using model-independent analysis methods in 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 time, together with individual plasma concentrations of ketorolac.

  Blood samples for PK analyses were obtained at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 hours post administration of ketorolac tromethamine

Study Arms (3)

Ketorolac Tromethamine

EXPERIMENTAL

Drug: Ketorolac Tromethamine

Oxymetazoline Hydrochloride

EXPERIMENTAL

Drug: Oxymetazoline Hydrochloride

Fluticasone Propionate

EXPERIMENTAL

Drug: Fluticasone Propionate

Interventions

Ketorolac Tromethamine DRUG

Single intranasal dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on Day 1 of Period 1

Ketorolac Tromethamine

Oxymetazoline Hydrochloride DRUG

Single intranasal dose of oxymetazoline hydrochloride followed by a single intranasal dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) 30 minutes later on Day 1 of Period 2

Oxymetazoline Hydrochloride

Fluticasone Propionate DRUG

Seven days of treatment with intranasal fluticasone propionate (between Periods 2 and 3) followed by a single intranasal dose of 30 mg ketorolac tromethamine (one 15 mg spray into each nostril) on Day 1 of Period 3

Fluticasone Propionate

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female volunteers, aged between 18 and 65 years inclusive
• Participant had a history of allergic rhinitis for which treatment had been required at least 3 days out of 7 within the last 3 months. Subjects who were symptomatic of allergic rhinitis but were not currently using therapy because they had found it ineffective may have been included
• Participant was otherwise considered to exhibit general good health, in the opinion of the Investigator
• Participants may have had known medical conditions that were considered "stable" and not expected to interfere with the study outcome or to be adversely affected by their involvement in the study. This was determined by the Investigator at the time of screening by the following:
• A pre-study physical examination with no clinically significant abnormalities
• Vital signs within normal ranges or outside the normal range but not deemed clinically significant in the opinion of the Investigator
• An electrocardiogram (ECG) with no clinically significant abnormalities
• Full medical history
• Participant had bilateral patent nasal airways at screening as assessed by the Investigator
• Participant had a body mass index (BMI) between 19 and 29 kg/m2
• Female participants of child bearing potential:
• Must have had a negative urine pregnancy test prior to entry into the study
• Must not have been breast feeding
• Participant must have been able to provide written informed consent
• Participant'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

You may not qualify if:

• Any known allergy or sensitivity to ketorolac tromethamine, oxymetazoline hydrochloride, fluticasone propionate or formulation ingredients
• Any history of co-existing nasal polyps, NSAID sensitivity and asthma
• Daily use of an intranasal decongestant medication
• 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
• Use of any non-prescribed drug in the 72 hours prior to study drug administration and during the study. Paracetamol use was not allowed within the 24 hours prior to Day 1 of each period. NSAIDs were restricted for at least 3 days or 5 half-lives, whichever was longer, prior to dosing on Day 1 of Period 1, and must not have been used throughout the study. Current prescribed medications were not discontinued prior to entry into the study or during study participation, unless known to interact with ketorolac as per the product information (injectable)
• 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
• Positive serum test for human immunodeficiency virus (HIV) or hepatitis B or C at screening
• Positive serum alcohol test at screening or on entry into the study
• Positive urine drug screen for any non-prescribed drugs of abuse (DOA) at screening or on entry into the study
• Clinically significant abnormality on screening laboratory tests
• History of cocaine use
• Concurrent use of ritonavir or other potent CYP3A4 inducers or inhibitors.
• Blood donation within 30 days of beginning study participation

Sponsors & Collaborators

• Egalet Ltd: lead

Study Sites (1)

Pain and Anaesthesia Research Clinic/Royal Adelaide Hospital

Adelaide, Australia

Location

MeSH Terms

Conditions

Rhinitis, Allergic

Interventions

Ketorolac Tromethamine; Oxymetazoline; Fluticasone

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: David Bregman, M.D., Ph.D.
• Organization: Luitpold Pharmaceuticals, Inc.

dbregman@lpicrd.com

610-650-4200

Study Officials

• Lincoln Bynum, MD

  ICON Developmental Solutions

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: June 1, 2011
• First Posted: June 3, 2011
• Study Start: December 1, 2007
• Primary Completion: February 1, 2008
• Study Completion: June 1, 2008
• Last Updated: March 6, 2018
• Results First Posted: July 23, 2015

Record last verified: 2018-03

Locations

AU (1)