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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01365650
• Date of registration: 01/06/2011
• Prospective Registration: No
• Primary sponsor: Egalet Ltd
• Public title: 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
• Scientific title: Open Label, Three-Way Study to Assess the Absorption and Tolerability of Intranasal Ketorolac Tromethamine and to Assess the Effects of a Single Dose of Oxymetazoline Hydrochloride and Multiple Doses of Fluticasone Propionate on the Absorption and Tolerability of Intranasal Ketorolac Tromethamine in Participants With Allergic Rhinitis
• Date of first enrolment: December 2007
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01365650
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: Lincoln Bynum, MD
• Affiliation: ICON Developmental Solutions

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- All female participants of child bearing potential and all male participants with
female partners of child bearing potential must have consented to use a medically
acceptable method of contraception (oral or implanted contraceptive hormones with
combined use of barrier contraception, condom or diaphragm with spermicidal agent,
intrauterine device, menopausal [defined as last menstrual period >12 months ago] or
surgical sterilization) throughout the study period and for a minimum of 4 weeks or 1
full menstrual cycle prior to inclusion

- 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

- Glomerular filtration rate >75 mL/minute as calculated using the Cockroft-Gault
calculation for creatinine clearance

Exclusion Criteria:

- 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

- 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

- Renal impairment or a risk for renal failure due to volume depletion.

- History of asthma or any other chronic pulmonary disorder, with the exception of
childhood asthma and asymptomatic asthma, which were assessed individually by the
Principal Investigator

- Current tobacco use or a past history of smoking > or = 5 pack-years within the last 5
years

- A history of any other clinically significant, unstable medical problem, which in the
opinion of the Investigator would have interfered with study participation

- Participation in another investigational drug study within 30 days of study entry, or
5 times the half-life of the investigational drug, whichever was longer

- Positive test for Helicobacter pylori (H. pylori) at screening



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Allergic Rhinitis

Intervention(s)

Drug: Fluticasone Propionate

Drug: Oxymetazoline Hydrochloride

Drug: Ketorolac Tromethamine

Primary Outcome(s)

MRT (the Mean Residence Time) [Time Frame: 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 0-8 (the AUC From Time Zero to Infinity, Where Possible) [Time Frame: 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]

Cmax (the Maximum Observed Plasma Concentration) [Time Frame: 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) [Time Frame: 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) [Time Frame: 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) [Time Frame: 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]

Secondary ID(s)

ROX 2007-03

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 23/07/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01365650