Asthma, AllergicPhase 4MAN06NCT02953106
Effects of Intranasal Fluticasone Plus Azelastine on Airway Inflammation in Patients With Asthma & Allergic Rhinitis
A Phase 4 study testing Azelastine-Fluticasone Nasal in people with Asthma, Allergic and Rhinitis,Allergic, run by University of Dundee at 1 site in United Kingdom.
Trial summary
Single centre, double-blind, placebo controlled, adaptive design, cross-over trial. The primary objective is to assess the additive effects of using combined intranasal fluticasone propionate plus azelastine nasal spray on airway hyperresponsiveness. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asthma, Allergic, Rhinitis,Allergic, Allergy
- What is being tested?
- Azelastine-Fluticasone Nasal
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Jan 2017to 10 Sep 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female volunteers, aged 18 years and above, with persistent asthma and allergic rhinitis
- On a minimum of 200μg BDP of Inhaled corticosteroid (ICS)
- FEV1 ≥ 60 % predicted
- Positive skin prick test, or record of elevated allergen-specific IgE to at least 1 perennial allergen
- Methacholine PC20 < 8mg/ml at Visit 1
- Ability to give informed consent
Who cannot join
- Other respiratory diseases such as COPD, bronchiectasis or allergic bronchopulmonary aspergillosis (ABPA) which are considered to be significant in the opinion of the study physician Nasal polyps ≥ Grade 2
- An asthma exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month of the study commencement, or 3 months if hospital admission was required
- Any clinically significant medical condition that may endanger the health or safety of the participant. For example: Patients who have tuberculosis or any type of untreated infection or have had recent surgical operation or injury to the nose or mouth.
- Participation in another trial within 30 days before the commencement of the study
- Pregnancy or lactation
- Unable to comply with the procedures of the protocol
Show all 9Show fewer
- Unable or unwilling to consent
- Taking prohibited medications as listed in section 6.7.2 Prohibited Medications
- Hypersensitivity to the active substances or to any of the excipients of Dymista Nasal Spray.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School
Dundee, Scotland, DD1 9SY
About this study
Official title: Proof of Concept Study to Assess Downstream Effects of Using Combined Intranasal Fluticasone Propionate Plus Azelastine Nasal Spray on Asthmatic Inflammation in Patients With Persistent Asthma and Allergic Rhinitis
Single centre, double-blind, placebo controlled, adaptive design, cross-over trial. The primary objective is to assess the additive effects of using combined intranasal fluticasone propionate plus azelastine nasal spray on airway hyperresponsiveness. This is in patients with persistent asthma and allergic rhinitis, receiving inhaled steroid.
Read the detailed description
The unified allergic airway describes patients who have both asthma and allergic rhinitis. Both conditions have similar underlying pathophysiology in terms of T-helper 2 (Th2) cell activation. Patients with unified allergic airway disease have a greater burden in terms of impaired quality of life, and the presence of airway hyper-responsiveness (AHR) to methacholine is a hallmark of their underlying asthmatic inflammatory process. Targeting the Th2 allergic airway with a topical antihistamine may improve airway hyperresponsiveness.
It has previously been shown that in patients with unified allergic airway disease, using inhaled fluticasone alone (100 micrograms per day) produced a 1.2 doubling dilution (dd) shift in the provocative concentration of methacholine required to reduce forced expiratory volume (FEV1) by 20% (PC20). However when adding nasal fluticasone to the inhaled steroid, there was a 1.79 dd shift. This difference (0.58 dd, 95% CI 0.78, 1.95) was not statistically significant. However the combined treatment did result in significant improvement in rhinitis quality of life, nasal inflammation and inspiratory flow.
The investigators will repeat this previous concept, but compare intranasal fluticasone with azelastine (an antihistamine) nasal spray versus placebo nasal spray, in atopic asthmatic patients on inhaled steroid. This will be to assess effects on methacholine PC20, the primary outcome, and to assess the effects on the following secondary outcomes: Exhaled nitric oxide (FeNO), FEV1, morning peak expiratory flow (PEF), impulse oscillometry, peak nasal inspiratory flow (PNIF), nasal nitric oxide (NO), blood eosinophils, eosinophilic cationic protein (ECP), nasal symptoms, asthma control and quality of life; and rhinitis quality of life.
Twenty adults 18 and up, with allergic asthma will be enrolled. They will have a run-in on 2 weeks of 200 micrograms beclometasone inhaler and then be randomised to add either intranasal fluticasone and azelastine, or placebo nasal spray to their treatment (double blind). Treatment period one will be 3-5 weeks followed by a washout of 2-4 weeks, and crossover to treatment period two for 3-5 weeks. Due to the crossover nature of this study participants will receive both treatments in random order. There will be an Interim analysis after 20 participants complete the study per protocol and the exact required sample size will be recalculated (Pocock/adaptive design).
- Conditions
- Asthma, Allergic, Rhinitis,Allergic, Allergy
- Being tested
- Azelastine-Fluticasone Nasal, Placebos
- Keywords
- Asthma, Rhinitis, Dymista, allergy
- Medical subject headings
- Asthma, Rhinitis, Allergic, Hypersensitivity, Rhinitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azelastine-Fluticasone NasalDrug
Also called Dymista
137 micrograms azelastine hydrochloride / 50 micrograms fluticasone propionate
PlacebosDrug
Placebo nasal spray
| Study group | Role | What they receive |
|---|---|---|
| Azelastine-Fluticasone Nasal | Active comparator | 137 micrograms azelastine hydrochloride / 50 micrograms fluticasone propionate per actuation. 1 squirt twice daily Receives: Drug: Azelastine-Fluticasone Nasal |
| Placebos | Placebo comparator | contains the same components as Dymista nasal spray with the exception of the active ingredients. 1 squirt twice daily. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Methacholine PC20
The provocative concentration of methacholine required to produce a 20% drop (PC20) in forced expiratory volume in 1 second (FEV1)
Measured: 3-5 weeks
Secondary outcomes (17)
Exhaled nitric oxide (FeNO)
A measurement of the amount of inflammation in the airways
Measured: 3-5 weeks
Forced expiratory volume in 1 second (FEV1)
The amount of air exhaled in the first second of a forced expiration.
Measured: 3-5 weeks
Morning peak expiratory flow (PEF)
A measurement of how quickly a patient can blow air out of their lungs
Measured: 3-5 weeks
Airway resistance at 5Hz (R5)
A measurement of the total airway resistance at the frequency of 5 Hertz
Measured: 3-5 weeks
Airway resistance at 20Hz (R20)
A measurement of the proximal airways resistance at the frequency of 20 Hertz
Measured: 3-5 weeks
Peripheral airway resistance (R5-R20)
A measurement of the peripheral airway resistance by taking the resistance at 5Hz and subtracting the resistance at 20 Hertz
Measured: 3-5 weeks
Airway Reactance (X5)
A measurement of the peripheral capacitive reactance at the frequency of 5 Hertz
Measured: 3-5 weeks
Airway Reactance area under the curve (AX)
A measurement of the reactance area between the negative reactance trend and zero.
Measured: 3-5 weeks
Domiciliary peak nasal inspiratory flow (PNIF)
A measurement of how open or blocked the nasal passages are.
Measured: 3-5 weeks
Nasal nitric oxide (NO)
A measurement of the amount of inflammation in the nasal passages.
Measured: 3-5 weeks
Blood eosinophils
A measurement of the amount of eosinophils in the blood
Measured: 3-5 weeks
Eosinophilic cationic protein (ECP)
A measurement of the amount of Eosinophilic Cationic Protein (ECP) in the blood
Measured: 3-5 weeks
Total nasal symptom score (TNS4)
A questionnaire to assess four (4) types of nasal symptoms: runny nose, blocked nose, itchy nose, and sneezing.
Measured: 3-5 weeks
Asthma control questionnaire (ACQ)
A questionnaire to measure the degree of a person's asthma control
Measured: 3-5 weeks
Asthma quality of life questionnaire (AQLQ)
A questionnaire to measure the functional problems that are most troublesome to adults with asthma.
Measured: 3-5 weeks
Rhinitis quality of life questionnaire (RQLQ)
A questionnaire to measure the functional problems that are most troublesome to adults with rhinitis.
Measured: 3-5 weeks
Visual analogue scale (VAS)
a 10 cm line horizontal describing rhinitis symptoms. zero being "not bothersome" and ten being "very bothersome".
Measured: 3-5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2016 (estimated)
- Study start20 Jan 2017
- Primary completion10 Sep 2018
- Study completion10 Sep 2018
Why it stopped: The company providing study IMP was unable to supply further batches of IMP.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asthma, AllergicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brian Lipworth, MD, Principal investigator, Scottish Centre for Respiratory Reseach
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02953106
- Sponsor's protocol ID
- 2015-001093-17
- Other IDs
- 2015
- Acronym
- MAN06
- Status last verified
- Apr 2019
- First submitted
- 28 Oct 2016
- Last updated
- 8 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof of Concept Study to Assess Downstream Effects of Using Combined Intranasal Fluticasone Propionate Plus Azelastine Nasal Spray on Asthmatic Inflammation in Patients With Persistent Asthma and Allergic Rhinitis
- ClinicalTrials.gov ID
- NCT02953106
- Acronym / sponsor ID
- MAN06 / 2015-001093-17
- Conditions
- Asthma, Allergic, Rhinitis,Allergic, Allergy
- Keywords
- Asthma, Rhinitis, Dymista, allergy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The company providing study IMP was unable to supply further batches of IMP.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Study start
- 20 Jan 2017 (actual)
- Primary completion
- 10 Sep 2018 (actual)
- Study completion
- 10 Sep 2018 (actual)
- First posted
- 2 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Single centre, double-blind, placebo controlled, adaptive design, cross-over trial. The primary objective is to assess the additive effects of using combined intranasal fluticasone propionate plus azelastine nasal spray on airway hyperresponsiveness. This is in patients with persistent asthma and allergic rhinitis, receiving inhaled steroid.
Detailed description
The unified allergic airway describes patients who have both asthma and allergic rhinitis. Both conditions have similar underlying pathophysiology in terms of T-helper 2 (Th2) cell activation. Patients with unified allergic airway disease have a greater burden in terms of impaired quality of life, and the presence of airway hyper-responsiveness (AHR) to methacholine is a hallmark of their underlying asthmatic inflammatory process. Targeting the Th2 allergic airway with a topical antihistamine may improve airway hyperresponsiveness.
It has previously been shown that in patients with unified allergic airway disease, using inhaled fluticasone alone (100 micrograms per day) produced a 1.2 doubling dilution (dd) shift in the provocative concentration of methacholine required to reduce forced expiratory volume (FEV1) by 20% (PC20). However when adding nasal fluticasone to the inhaled steroid, there was a 1.79 dd shift. This difference (0.58 dd, 95% CI 0.78, 1.95) was not statistically significant. However the combined treatment did result in significant improvement in rhinitis quality of life, nasal inflammation and inspiratory flow.
The investigators will repeat this previous concept, but compare intranasal fluticasone with azelastine (an antihistamine) nasal spray versus placebo nasal spray, in atopic asthmatic patients on inhaled steroid. This will be to assess effects on methacholine PC20, the primary outcome, and to assess the effects on the following secondary outcomes: Exhaled nitric oxide (FeNO), FEV1, morning peak expiratory flow (PEF), impulse oscillometry, peak nasal inspiratory flow (PNIF), nasal nitric oxide (NO), blood eosinophils, eosinophilic cationic protein (ECP), nasal symptoms, asthma control and quality of life; and rhinitis quality of life.
Twenty adults 18 and up, with allergic asthma will be enrolled. They will have a run-in on 2 weeks of 200 micrograms beclometasone inhaler and then be randomised to add either intranasal fluticasone and azelastine, or placebo nasal spray to their treatment (double blind). Treatment period one will be 3-5 weeks followed by a washout of 2-4 weeks, and crossover to treatment period two for 3-5 weeks. Due to the crossover nature of this study participants will receive both treatments in random order. There will be an Interim analysis after 20 participants complete the study per protocol and the exact required sample size will be recalculated (Pocock/adaptive design).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azelastine-Fluticasone Nasal | Active comparator | Drug: Azelastine-Fluticasone Nasal137 micrograms azelastine hydrochloride / 50 micrograms fluticasone propionate per actuation. 1 squirt twice daily |
| Placebos | Placebo comparator | Drug: Placeboscontains the same components as Dymista nasal spray with the exception of the active ingredients. 1 squirt twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female volunteers, aged 18 years and above, with persistent asthma and allergic rhinitis
- On a minimum of 200μg BDP of Inhaled corticosteroid (ICS)
- FEV1 ≥ 60 % predicted
- Positive skin prick test, or record of elevated allergen-specific IgE to at least 1 perennial allergen
- Methacholine PC20 < 8mg/ml at Visit 1
Key exclusion criteria (9 listed)
- Other respiratory diseases such as COPD, bronchiectasis or allergic bronchopulmonary aspergillosis (ABPA) which are considered to be significant in the opinion of the study physician Nasal polyps ≥ Grade 2
- An asthma exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month of the study commencement, or 3 months if hospital admission was required
- Any clinically significant medical condition that may endanger the health or safety of the participant. For example: Patients who have tuberculosis or any type of untreated infection or have had recent surgical operation or injury to the nose or mouth.
- Participation in another trial within 30 days before the commencement of the study
- Pregnancy or lactation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azelastine-Fluticasone NasalAlso: Dymista137 micrograms azelastine hydrochloride / 50 micrograms fluticasone propionate | Drug | Azelastine-Fluticasone Nasal |
| PlacebosPlacebo nasal spray | Drug | Placebos |
Primary outcome
Methacholine PC20
Time frame: 3-5 weeks
The provocative concentration of methacholine required to produce a 20% drop (PC20) in forced expiratory volume in 1 second (FEV1)
17 secondary outcomes
Exhaled nitric oxide (FeNO)
Time frame: 3-5 weeks
Forced expiratory volume in 1 second (FEV1)
Time frame: 3-5 weeks
Morning peak expiratory flow (PEF)
Time frame: 3-5 weeks
Airway resistance at 5Hz (R5)
Time frame: 3-5 weeks
Airway resistance at 20Hz (R20)
Time frame: 3-5 weeks
Peripheral airway resistance (R5-R20)
Time frame: 3-5 weeks
Airway Reactance (X5)
Time frame: 3-5 weeks
Airway Reactance area under the curve (AX)
Time frame: 3-5 weeks
Domiciliary peak nasal inspiratory flow (PNIF)
Time frame: 3-5 weeks
Nasal nitric oxide (NO)
Time frame: 3-5 weeks
Blood eosinophils
Time frame: 3-5 weeks
Eosinophilic cationic protein (ECP)
Time frame: 3-5 weeks
Total nasal symptom score (TNS4)
Time frame: 3-5 weeks
Asthma control questionnaire (ACQ)
Time frame: 3-5 weeks
Asthma quality of life questionnaire (AQLQ)
Time frame: 3-5 weeks
Rhinitis quality of life questionnaire (RQLQ)
Time frame: 3-5 weeks
Visual analogue scale (VAS)
Time frame: 3-5 weeks
Results and safety
The study was stopped early (reason given: The company providing study IMP was unable to supply further batches of IMP.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian Lipworth, MD principal investigator
Scottish Centre for Respiratory Reseach
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azelastine-Fluticasone Nasal in people with Asthma, Allergic and Rhinitis,Allergic, run by University of Dundee at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The company providing study IMP was unable to supply further batches of IMP.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Methacholine PC20 (time frame: 3-5 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2019.