The aim of this study is to investigate if bidirectional delivery, by delivering more drug to the region of the sinus ostia, improves upon the efficacy of current nasal steroids in chronic rhinosinusitis.to get information about the efficacy, safety…
ID
Source
Brief title
Condition
- Upper respiratory tract disorders (excl infections)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy Parameters:
·Change from baseline to last visit (Visit 5) in Visual Analogue Scale (VAS)
overall symptom score for chronic rhinosinusitis. Change from baseline to other
timepoints will be a secondary endpoint.
·Change from baseline to each visit in the Clinician assessment of nasal
blockage on nasendoscopy using the Lund and Mackay scoring system.
·Monthly change from baseline (mean daily score over the last 7 days of run-in)
in morning and evening combined averaged symptom score for each month from
patient Diary.
·Change from baseline to each visit in the Rhinosinusitis Outcome Measure 31
(RSOM-31).
·The change from baseline in the inflammatory mucosa measured using magnetic
resonance imaging (MRI) at 12 weeks.
·Change from baseline to each visit in nasal volume and cross-sectional area
measured using acoustic rhinometry.
·Change from baseline to each visit in peak nasal inspiratory flow (PNIF)
·Use of rescue medication.
Secondary outcome
Safety Parameters:
·Adverse events
·Vital signs
·Clinical laboratory tests (hematology, clinical chemistry, urinalysis)
·Morning plasma cortisol concentration
·physical examination.
Background summary
A phase IIa, single centre, randomised, prospective, double-blind, parallel
group study. Patients will be divided into two treatment groups; one group that
will receive fluticasone propionate, the other group the placebo. The OptiNose
device is primed and positioned in one nostril and the subject blows into the
mouthpiece of the device. This exhalation against the resistance of the device
closes the soft palate due to positive pressure, so separating the nasal and
oral cavities and avoiding lung deposition which enables smaller particles to
be delivered. In addition, it establishes bi-directional airflow through the
nose. Blowing through the device triggers the breath-actuation mechanism and
releases the dose from the nasal spray. After this 12 week-study, results of
the two treatments will be compared and analysed to judge if the fluticasone
propionate and the way of admission really is a benefit for the patient.
Study objective
The aim of this study is to investigate if bidirectional delivery, by
delivering more drug to the region of the sinus ostia, improves upon the
efficacy of current nasal steroids in chronic rhinosinusitis.
to get information about the efficacy, safety and tolerability of fluticasone
propionate using the OptiNose device in subjects with chronic rhinosinusitis.
Study design
A phase IIa, single centre, randomised, prospective, double-blind, parallel
group, placebo-controlled study.
Intervention
Half of the group (20 subjects) will receive 400 micrograms twice dialy (total
daily dose of 800 micrograms) of the investigated productl (Fluticasone
Propionate) and the other half will receive placebo twice dialy .
Study burden and risks
Three risks with consequent precautions need to be highlighted:
In very rare cases (<1/10,000), hypersensitivity reactions, with respiratory
symptoms (bronchospasm) and anaphylactic reactions have been reported. These
manifestations might become very serious and even life-threatening. As a
precaution, the protocol dictates that special mention will be made to the
subject that there have been very rare reports of a severe allergic reaction to
fluticasone propionate. If any subject suddenly develops a rash, swelling
(usually of the face, lips or tongue) or difficulty with breathing, the subject
should stop using the study medication and contact the Principal Investigator
immediately. All subjects should be asked specifically if they have experienced
prior reactions to fluticasone propionate. AEs associated with nasal
administration of fluticasone propionate are presented in Table 6.
The bioavailability of and hence systemic exposure to fluticasone is expected
to be far below any levels that can give systemic side-effects and adverse
events. However, it is important that the subjects do not take any potent
P450/CYP 3A inhibitors (which can increase the fluticasone propionate plasma
concentrations several hundred fold, resulting in marked suppression of serum
cortisol concentrations). As a precaution, subjects that are receiving any
P450/CYP 3A inhibitor are to be excluded.
Although the clinical data indicate otherwise, there is a theoretical
possibility that fluticasone propionate can lead to developmental and
birth-defects. Therefore, pregnant subjects, or subjects that might become
pregnant, must be excluded.
See Table 6 Expected Adverse Events
As with other nasal sprays, unpleasant taste and smell and headache have been
reported.
As with other nasal sprays, dryness and irritation of the nose and throat, and
epistaxis have been reported.
Nasal septal perforation has also been reported following the use of intranasal
corticosteroids.
Systemic effects of some nasal corticosteroids may occur, particularly when
prescribed at high doses for prolonged periods.
Undesirable effects resulting from Flixonase Aqueous Nasal Spray (SPC).
Frequencies are defined as: very common (>1/10), common (>1/100 and <1/10),
uncommon (>1/1000 and <1/100), rare (>1/10,000 and <1/1000) and very rare
(<1/10,000) including isolated reports. Very common, common and uncommon events
were generally determined from clinical trial data. Rare and very rare events
were generally determined from spontaneous data. In assigning adverse event
frequencies, the background rates in placebo groups were not taken into
account.
South Marston Park
Wiltshire SN3 4TG
Verenigd Koninkrijk
South Marston Park
Wiltshire SN3 4TG
Verenigd Koninkrijk
Listed location countries
Age
Inclusion criteria
- Male and female subjects aged between 18 and 65 years of age.
- Subjects must have chronic rhinosinusitis which is defined as at least 12 weeks history of two or more of:
* Blockage/congestion
* Discharge: anterior/post nasal drip
* Facial pain/pressured
* Reduction or loss of smell
And either:
* Mucopurulent discharge from the middle meatus or
* Edema/mucosal obstruction primarily in the middle meatus.
- Subjects must have no clinically significant abnormal serum biochemistry, haematology and urine examination values on screening.
- Subjects must have verified airflow through both nostrils and an ability to close their soft palate.
- The subject must have the ability to create bi-directional flow using a placebo OptiNose device with a nasal outflow of >20 L/min.
- The subject must have the ability to trigger the Breath Actuation Mechanism of an OptiNose device in accordance with the Instructions For Use.
Exclusion criteria
- Subjects who have visible pedunculated polyps on nasal endoscopy.
- Subjects who have undergone surgical treatment for nasal polyps during the previous 3 months.
- Subjects with a diagnosis of cystic fibrosis.
- Subjects with other disease likely to interfere with the study parameters, evidence of any serious or unstable concurrent disease or psychological disorder.
- A hypersensitivity or contraindication to steroids or any excipients.
- Subjects who have received depot or oral steroids during the previous 3 months.
- Subjects with a requirement for more than 1000 µg beclomethasone (or equivalent) per day for the treatment of asthma.
- Subjects taking inhaled steroids who have not been on a stable dose for 3 months or more.
- Subjects who are unable to cease treatment with intranasal steroids, or intranasal sodium cromoglycate, decongestants or antihistamines at the Screening Visit.
- Subjects currently receiving leukotriene receptor antagonists, nasal atropine or ipratropium bromide, beta blockers or neuroleptics.
- Subjects who are unable to cease treatment with saline rinsing at the Screening Visit.
- Subjects using devices that dilate the nostrils to improve nasal breathing.
- Subjects being treated with ritonavir or other potent CYP3A inhibitors as listed in Appendix 2 of the protocol due to the potential for greatly increased fluticasone plasma concentrations.
- Subjects with a history of operations where metal objects were used and retained in the body or those with a pacemaker or other implants e.g. cochlear implants and artificial heart valves.
- Subjects with a history of a penetrating injury to the eye with a metal object or those who have worked with metal at high speed.
- A history of drug or alcohol abuse.
- Subjects with an inability to communicate well with the investigator (i.e. language problem,poor mental development or impaired cerebral function)
- Subjects with a cleft palate.
- Subjects who have participated in a New Chemical Entity study within the previous 16 weeks or a marketed drug study within the previous 12 weeks.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-006341-13-NL |
| CCMO | NL15630.018.07 |