The objective of this study is to evaluate the safety and efficacy of two doses of FFNS (110 mcg once daily and 110 mcg twice daily) compared to placebo as monotherapy in the treatment of adult and adolescent subjects 12 years of age and older with…
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Source
Brief title
Condition
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint for the study is the mean change from baseline in
daily major symptom score (MSS) over the entire treatment period. The MSS is
the sum of three individual symptom scores for (1) nasal congestion/stuffiness,
(2) sinus headache/pressure or facial pain/pressure, and (3) postnasal drip
that are rated by the subject using a 0 to 3 scale.
Secondary outcome
The key secondary endpoint is the first time to symptom improvement. Symptom
improvement is defined as reduction of individual symptom scores of nasal
congestion/stuffiness, sinus headache/pressure or facial pain/pressure, and
postnasal drip to * 1 for 2 consecutive 12-hour assessments.
Other secondary endpoints will include the mean change from baseline over the
entire treatment period in AM and PM MSS and daily, AM, and PM individual
symptom scores for nasal congestion/stuffiness, sinus headache/pressure or
facial pain/pressure and postnasal drip, and the percentage of subjects who
require the use of an antibiotic during the study due to the development of
fulminant bacterial rhinosinusitis.
Health outcome measures include Sino-Nasal Outcome Test -20 (SNOT-20) and daily
productivity and sleep diary questions.
Safety endpoints include adverse events, clinical laboratory tests, vital
signs, and nasal examinations.
Background summary
Acute rhinosinusitis (ARS) is a condition caused by inflammation of the nose
and the paranasal sinuses that generally lasts up to 4 weeks. Despite ARS
being a self-limiting condition, untreated or inadequately treated sinus
infection can lead to the development of complications. Uncomplicated ARS is a
subset of ARS and is distinguished from the common cold by the persistence or
the worsening of sinus inflammation after the usual period for recovery of
viral infection of the nasal cavity (i.e., 10 days). Clinically the difference
is based on the following criteria: symptoms are present at least 10 days but
less than 4 weeks beyond the onset of upper respiratory symptoms OR symptoms
worsen after 5 days from their onset. Uncomplicated ARS is further
differentiated from fulminant bacterial rhinosinusitis by the absence of severe
headache/facial/sinus pain and temperature > 38oC.
In the primary care settings, ARS is often treated empirically with antibiotics
although they are shown to provide limited benefit in the uncomplicated ARS
population. Alternatively, the use of an intranasal corticosteroid (INS) to
control symptoms of uncomplicated ARS is plausible based on clinically proven
ability to reduce inflammation and mucosal swelling. Indeed, data from recent
studies in adults and adolescents have shown that the use of INS treatment as
monotherapy or in conjunction with antibiotics provided efficacy in symptom
reductions and improved recovery rates when treating ARS. Currently, only one
INS, mometasone furoate, is approved in Canada for treating uncomplicated ARS
as monotherapy, whereas there is no INS approved in Europe for this condition.
This study is a phase IIb dose finding study and one of two pivotal studies
that will constitute the fluticasone furoate nasal spray (FFNS) global clinical
development program to support an indication for the treatment of uncomplicated
ARS by FFNS. The optimal dose in treating uncomplicated ARS will be selected
based on the results from this study and used for a subsequent confirmatory
phase III study.
Study objective
The objective of this study is to evaluate the safety and efficacy of two doses
of FFNS (110 mcg once daily and 110 mcg twice daily) compared to placebo as
monotherapy in the treatment of adult and adolescent subjects 12 years of age
and older with uncomplicated ARS.
Study design
This is a randomized, double-blind, placebo controlled, parallel group,
multi-centre, 2-week treatment study. The study includes a 2-week
post-treatment follow-up period.
Approximately 720 subjects will be randomized to one of three treatment groups
for a period of 14 days: FFNS 110 mcg QD, FFNS 110 mcg BID, and placebo nasal
spray. The randomization will be stratified by country, age (<18 years, >/=18
years), and allergic rhinitis (AR) status (Yes/No) based on documented skin
prick test or in vitro blood test results.
Subjects who have ARS symptoms for 5-8 days will attend the study clinic for
Visit 1 (screening visit) and subsequently enter 3 days of a screening period
(with a permitted window of +2 days) during which they will record symptom
scores twice daily (morning and evening) starting on the evening of Visit 1 and
with the last assessment on the morning of Visit 2. Subjects who meet symptom
requirements as well as other study entry criteria will be assigned to one of
three study treatments at Visit 2 (Day 1) and start a 2-week study treatment.
Subjects will attend the study clinic for Visits 3, 4 and 5 on Day 8 +/- 2 (end
of 1-week treatment), Day 15 + 2 (end of 2-week treatment) and Day 22 +/- 2
(1-week post-treatment follow-up), respectively. Subjects will receive a
follow-up telephone contact 7 days after Visit 5 to assess any post-treatment
adverse events.
Intervention
Treatment with fluticasone furoate or placebo.
Study burden and risks
Risk: Adverse effects of study medication.
Burden: 5 visits and 1 telephone contact in 4 weeks.
Physical examination 2x, nasal examination 5x.
Blood tests safety 2x, total volume approx. 20 ml. Pharmacogenetic blood
sample10 ml 1x (optional). Urine tests 2x. Allergy test (skin or blood) 0-1x.
Pregnancy test 3x. Questionnaire 3x. Diary (symptoms, use of study medication)
3 weeks.
Huis ter Heideweg 62
3705 LZ Zeist
Nederland
Huis ter Heideweg 62
3705 LZ Zeist
Nederland
Listed location countries
Age
Inclusion criteria
• Age >= 12 years.
• Subject has provided an informed consent to participate. An appropriately signed and dated consent must be obtained from the parents or guardian of a subject who is under the legal age of consent.
• Diagnosis of uncomplicated acute rhinosinusitis
Subject has two or more major symptoms of uncomplicated acute rhinosinusitis [nasal congestion/stuffiness, sinus headache/pressure or facial pain/pressure, and postnasal drip];
• One symptom must be sinus headache/pressure or facial pain/pressure; and
• Subject has experienced symptoms for at least 5 days and no more than 8 days prior to the screening visit (Visit 1).
Exclusion criteria
• Based on the investigator*s clinical judgement, subject has fulminant bacterial rhinosinusitis during the screening period including Visits 1 and 2.
• Acute rhinosinusitis in the past 12 weeks.
• Other sinonasal conditions in past 3 years.
• Allergic rhinitis.
• Influenza, candida-infection or ulcerations of the nose, otitis media.
• Obstructions like septumdeviation of polips.
• Antibiotica airway infections in the past 30 days.
• Use of analgecs (past 24 hours), corticosteroids (intranasal 4 weeks, others 8 weeks), other drugs infuencing nasal symptoms (detailed specification: see protocol).
• Swokers.
• Pregnancy and lactation.
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| Other | Clinicaltrials.gov; registratienummer nog niet bekend. |
| EudraCT | EUCTR2009-015014-22-NL |
| CCMO | NL30481.003.09 |