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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01365650




Registration number
NCT01365650
Ethics application status
Date submitted
1/06/2011
Date registered
3/06/2011
Date last updated
6/03/2018

Titles & IDs
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
Secondary ID [1] 0 0
ROX 2007-03
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Allergic Rhinitis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Allergies
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ketorolac Tromethamine
Treatment: Drugs - Oxymetazoline Hydrochloride
Treatment: Drugs - Fluticasone Propionate

Experimental: Ketorolac Tromethamine -

Experimental: Oxymetazoline Hydrochloride -

Experimental: Fluticasone Propionate -


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

Treatment: Drugs: Oxymetazoline Hydrochloride
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: Drugs: Fluticasone Propionate
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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
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
Primary outcome [4] 0 0
AUC 0-8 (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.
Timepoint [4] 0 0
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
Primary outcome [5] 0 0
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.
Timepoint [5] 0 0
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
Primary outcome [6] 0 0
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.
Timepoint [6] 0 0
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

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Pain and Anaesthesia Research Clinic/Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
- Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Egalet Ltd
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01365650
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Lincoln Bynum, MD
Address 0 0
ICON Developmental Solutions
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications