CoughEarly Phase 1NCT05955885
Effect of Over-the-counter NSAIDS on Cough Reflex Sensitivity in Patients with Upper Respiratory Tract Infections
A Early Phase 1 study testing Flurbiprofen Oral Lozenge, Difflam and Flurbiprofen 8.75 MG in people with Cough and Upper Respiratory Tract Infections, run by University of Melbourne at 1 site in Australia.
Trial summary
The goal of this mechanism of disease study is to investigate the effect of flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), on the cough hypersensitivity associated with upper respiratory tract infections (URTI). Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Cough, Upper Respiratory Tract Infections
- What is being tested?
- Flurbiprofen Oral Lozenge, Difflam and Flurbiprofen 8.75 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 101 participants
- Where
- 1 siteAustralia
- Study dates
- 1 Jul 2023to 1 Jul 2024
- Phase
- Early Phase 1
- 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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- An onset of any 2 URTI symptoms in past 3-5 days, such as a sore throat, fever, coughing, coughing up phlegm, sneezing, and runny nose;
- A current cough or urge-to-cough rated at least 5 in severity and/or ranking cough as subject's most bothersome symptom on Cold Symptoms Questionnaire (CSQ);
- A feeling of sickness interfering with their daily life, rated as at least mildly;
- A cough consistent with acute cough - i.e., cough onset with URTI and not ongoing, chronic cough;
- Written informed consent and a willingness and ability to comply with the study protocol.
Who cannot join
- A pre-existing chronic lung disease (asthma, COPD, chronic bronchitis etc), to exclude these as causes for cough;
- The use of inhaled or systemic steroids / broncho-active medication, ACE inhibitors, oral or inhaled antihistamines, opiates, gabapentin, tricyclic antidepressants (current or within the past 3 months), as these will alter airway inflammatory profiles and/ or cough sensitivity;
- A current cigarette or marijuana smoker/vaper, recreational drug user, or have given up smoking/vaping within the last 12 months, or a former smoker with greater than 20 pack-years, alter airway inflammatory profiles and/ or cough sensitivity;
- Pre-existing chronic cough (cough persisting for more than 8 weeks): unexplained chronic cough (UCC) or refractory chronic cough (RCC) associated with or without a pre-existing condition (GERD, rhinitis, etc), as we are studying acute cough;
- Prior experience of an allergic or bad reaction to capsaicin or chilli (which is rare);
- Prior experience an allergic or bad reaction to a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen;
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- Ongoing or history of stomach ulcer, impaired kidney or liver function, or heart failure;
- Pregnancy, lactation or actively trying to become pregnant;
- Currently taking other products with flurbiprofen, aspirin or other anti-inflammatory medicines;
- Evidence of COVID-19 positivity, either during the COVID Rapid Antigen Test administered on the day of assessment or have informed us that they have become positive in the 24-48 hours after the testing session (i.e., participants who were likely positive during assessment but under the detection threshold);
- Participants who cannot provide informed voluntary consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Over-the-counter Non-steroidal Anti-inflammatory Treatments on Cough Reflex Sensitivity in Subjects with Upper Respiratory Tract Infection
The goal of this mechanism of disease study is to investigate the effect of flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), on the cough hypersensitivity associated with upper respiratory tract infections (URTI).
The main questions it aims to answer are:
Read more
- Q1: Does a single treatment with an approved therapeutic dose of flurbiprofen, an NSAID that prevents the production of prostaglandins, acutely reduce objective measures of cough hypersensitivity in participants with URTI?
- Q2: Is the effect of flurbiprofen on cough hypersensitivity in URTI related to participant subjective ratings of acute cough severity?
- Q3: Is the effect of flurbiprofen on cough hypersensitivity in URTI related to the levels of prostaglandins or other inflammatory markers measurable in upper airway secretions?
Participants will be asked to undergo cough challenge testing, complete quality of life questionnaires, and have their nasal fluid, saliva and pharyngeal secretions sampled before and after a single treatment with flurbiprofen in the form of a lozenge or spray. Participants in the comparator arms of the study will instead receive a placebo lozenge or low dose flurbiprofen spray.
Read the detailed description
People with an Upper Respiratory Tract Infection (URTI), for example the common cold, often exhibit heightened sensitivity to stimuli that cause coughing. This heightened sensitivity is thought to contribute to the short-term excessive coughing that accompanies the infection. What causes the heightened sensitivity is not known but may involve inflammation in the throat.
HYPOTHESIS: The investigators hypothesise that in URTI prostaglandins may lead to cough hypersensitivity by either a direct or indirect action on cough nerve fibre endings in the larynx, lowering their activation threshold to cough stimuli.
OVERALL AIM: This study aims to investigate this hypothesis by assessing whether a single treatment with flurbiprofen, an existing over the counter anti-inflammatory drug (NSAID) medication contained in some 'cold and flu remedies' and used to relieve sore throat in URTI, reduces heightened cough sensitivity through a reduction in throat inflammation. The investigators will recruit 120 otherwise healthy male and female adults experiencing an URTI with acute cough for laboratory assessments lasting 5-6 hours.
OBJECTIVES: The primary objective is to assess whether flurbiprofen, in commercially available lozenge or spray formulations, reduces an individual's sensitivity to a cough evoking stimulus by assessing participant responsiveness to inhaled capsaicin. Capsaicin is the naturally occurring 'hot' component of chilli peppers and commonly used to investigate the cough reflex in humans.
The secondary objectives are to assess the effect of flurbiprofen on:
- subjective measures of cough and urge-to-cough using questionnaires that assess Patient Reported Outcomes (PROs); and, B. the levels of chemical mediators of inflammation present in nasal secretions and saliva, to investigate flurbiprofen's potential mechanism of action.
METHOD: The investigators will test the hypothesis by measuring in participants their cough thresholds, subjective experiences with cough and urge-to-cough, and levels of airway prostaglandins and other inflammatory mediators, before and after a single treatment of flurbiprofen, which blocks the production of prostaglandins.
- Conditions
- Cough, Upper Respiratory Tract Infections
- Being tested
- Flurbiprofen Oral Lozenge, Difflam, Flurbiprofen 8.75 MG
- Keywords
- Cough, Cough sensitivity, Urge to cough, Respiratory tract infection, Non-steroidal anti-inflammatory drug, Mechanism of disease
- Medical subject headings
- Cough, Respiratory Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flurbiprofen Oral LozengeDrug
Also called Strepfen Intensive Lozenge - Honey and Lemon Flavour
This commercially available, over-the-counter lozenge manufactured by Reckitt Benckiser contains flurbiprofen as the active ingredient and is registered for the short-term treatment of sore throat associated with upper respiratory tract infections in people over the age of 12 years.
DifflamDrug
Also called Difflam Soothing Drops + Immune Support Honey & Lemon Flavour
This is a non-medicated, control lozenge that is the same flavour as the experimental lozenge that is marketed to help soothe dry, tickly throats while supporting the body's immune health.
Flurbiprofen 8.75 MGDrug
Also called Strepfen Intensive Oromucosal Spray; Strepsils Intensive Oromucosal Spray
This commercially available, over-the-counter spray manufactured by Reckitt Benckiser contains flurbiprofen as the active ingredient and is registered for the short-term treatment of sore throat associated with upper respiratory tract infections in people over the age of 12 years. It requires 3 actuations of the spray to deliver the full 8.75 dose. Here, a low dose control can be delivered by only performing 1 actuation of the spray.
| Study group | Role | What they receive |
|---|---|---|
| Flurbiprofen Oral Lozenge | Experimental | 30 participants will be asked to suck one (1) flurbiprofen 8.75 mg honey and lemon lozenge (tradename: Strepfen) until dissolved. Receives: Drug: Flurbiprofen Oral Lozenge |
| Placebo lozenge | Placebo comparator | 30 participants will be asked to suck one (1) non-medicated Difflam Soothing Drops + Immune Support Honey \& Lemon flavour lozenge until dissolved. Receives: Drug: Difflam |
| Flurbiprofen 8.75 MG | Experimental | 30 participants will be asked to perform three (3) oral actuations (2.91 mg per actuation) of flurbiprofen 8.75mg spray. Receives: Drug: Flurbiprofen 8.75 MG |
| Low dose flurbiprofen spray | Other | 30 participants will be asked to perform one (1) oral actuation of flurbiprofen 8.75 mg spray, equivalent to a 2.91mg dosage. This will serve a a low dose control as there is no placebo spray available. Receives: Drug: Flurbiprofen 8.75 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in objective measures of cough sensitivity
Participants' cough sensitivity thresholds will be measured by inhaled cough challenge testing. This involves participants inhaling single breaths of increasing concentrations of a tussigenic stimulus (capsaicin; (active component of hot chili peppers) as well as saline control to determine threshold doses that elicit an urge to cough, two coughs (C2) and five coughs (C5). The principal endpoint is measured as the change in capsaicin concentration needed to elicit cough responses and the unit of measure is micromolar.
Measured: Cough challenge testing will be performed at baseline and 3 hours after intervention.
Secondary outcomes (5)
Change in Cold Symptoms Questionnaire (CSQ) score
Participants will be asked to self-report on their cold symptom severity using the Cold Symptoms Questionnaire. Each item requires rating on a 10-point Likert scale from 1 to 10. A higher score indicates a worse outcome. The principal endpoint is measured as the change in Cold Symptoms Questionnaire score and the unit of measure is points.
Measured: Participant self-reports using the Cold Symptoms Questionnaire at baseline and every 30 min after invention until 3 hours has elapsed.
Change in levels of inflammatory markers in nasal fluid samples
Samples of nasal fluid will be taken from participants and levels of inflammatory markers such as prostaglandins will be measured using liquid chromatography-mass spectroscopy. The principle endpoint is measured as change in levels and the unit of measure is points. A higher score indicates a better outcome.
Measured: Nasal fluid samples will be taken at baseline and at 3 hours post-intervention.
Change in levels of inflammatory markers in saliva samples
Samples of saliva will be taken from participants and levels of inflammatory markers such as prostaglandins will be measured using liquid chromatography-mass spectroscopy. The principle endpoint is measured as change in levels and the unit of measure is points. A higher score indicates a better outcome.
Measured: Saliva samples will be taken at baseline and at 3 hours post-intervention.
Change in levels of inflammatory markers in pharyngeal lavage samples
Samples of pharyngeal fluid and tissue will be collected from a lavage and levels of inflammatory markers such as prostaglandins will be measured using liquid chromatography-mass spectroscopy. The principle endpoint is measured as change in levels and the unit of measure is points. A higher score indicates a better outcome.
Measured: Pharyngeal lavage samples will be taken at baseline and at 3 hours post-intervention.
Patients' Global Impression of Change score
Participants will self-report on their overall impression of whether the intervention they received resulted in any perceivable changes in their coughing/urge-to-cough. This questionnaire contains mixed items, including items that require rating of degree of change of symptoms on a 10 point Likert scale. The principal endpoint is the score for each item and the unit of measure is points.A higher score indicates a worse outocme.
Measured: Participants self-report using the Patients' Global Impression of Change score at 3 hours post-intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2023
- Study start1 Jul 2023
- Primary completion1 Jul 2024
- Study completion1 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for CoughStudies 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 120 participants will be randomised into four study arms, i.e. treatment with: 1. flurbiprofen lozenge 2. placebo lozenge 3. flurbiprofen spray 4. low dose flurbiprofen spray Regardless of which arm they are assigned to, each participant will undergo cough challenge testing to test cough sensitivity, fill out quality of life questionnaires, and have their nasal fluid, saliva and pharyngeal fluid sampled for inflammatory markers before and after the intervention.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Melbourne
- Sponsor type
- University, hospital or other
- Collaborators
- Reckitt Benckiser LLC
- Responsible party
- Principal investigator, Stuart Mazzone, University of Melbourne
- Investigators
- Stuart Mazzone, PhD, Principal investigator, University of Melbourne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05955885
- Sponsor's protocol ID
- 25925
- Status last verified
- Dec 2024
- First submitted
- 11 Jul 2023
- Last updated
- 6 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mazzone SB, Farrell MJ. Heterogeneity of cough neurobiology: Clinical implications. Pulm Pharmacol Ther. 2019 Apr;55:62-66. doi: 10.1016/j.pupt.2019.02.002. Epub 2019 Feb 11.
PubMed 30763726Farrell MJ, Mazzone SB. Are neural pathways processing airway inputs sensitized in patients with cough hypersensitivity? Pulm Pharmacol Ther. 2019 Aug;57:101806. doi: 10.1016/j.pupt.2019.101806. Epub 2019 May 15.
PubMed 31100512Dicpinigaitis PV. Effect of viral upper respiratory tract infection on cough reflex sensitivity. J Thorac Dis. 2014 Oct;6(Suppl 7):S708-11. doi: 10.3978/j.issn.2072-1439.2013.12.02.
PubMed 25383204Driessen AK, McGovern AE, Narula M, Yang SK, Keller JA, Farrell MJ, Mazzone SB. Central mechanisms of airway sensation and cough hypersensitivity. Pulm Pharmacol Ther. 2017 Dec;47:9-15. doi: 10.1016/j.pupt.2017.01.010. Epub 2017 Jan 27.
PubMed 28137663Renner B, Mueller CA, Shephard A. Environmental and non-infectious factors in the aetiology of pharyngitis (sore throat). Inflamm Res. 2012 Oct;61(10):1041-52. doi: 10.1007/s00011-012-0540-9. Epub 2012 Aug 14.
PubMed 22890476Lambkin-Williams R, Mann A, Shephard A. Inhibition of viral and bacterial trigger-stimulated prostaglandin E2 by a throat lozenge containing flurbiprofen: An in vitro study using a human respiratory epithelial cell line. SAGE Open Med. 2020 Sep 24;8:2050312120960568. doi: 10.1177/2050312120960568. eCollection 2020.
PubMed 33029351Schachtel BP, Homan HD, Gibb IA, Christian J. Demonstration of dose response of flurbiprofen lozenges with the sore throat pain model. Clin Pharmacol Ther. 2002 May;71(5):375-80. doi: 10.1067/mcp.2002.124079.
PubMed 12011823Schachtel B, Aspley S, Shephard A, Shea T, Smith G, Sanner K, Savino L, Rezuke J, Schachtel E. Onset of action of a lozenge containing flurbiprofen 8.75 mg: a randomized, double-blind, placebo-controlled trial with a new method for measuring onset of analgesic activity. Pain. 2014 Feb;155(2):422-428. doi: 10.1016/j.pain.2013.11.001. Epub 2013 Nov 12.
PubMed 24231654
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Over-the-counter Non-steroidal Anti-inflammatory Treatments on Cough Reflex Sensitivity in Subjects with Upper Respiratory Tract Infection
- ClinicalTrials.gov ID
- NCT05955885
- Acronym / sponsor ID
- 25925
- Conditions
- Cough, Upper Respiratory Tract Infections
- Keywords
- Cough, Cough sensitivity, Urge to cough, Respiratory tract infection, Non-steroidal anti-inflammatory drug, Mechanism of disease
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- University of MelbourneUniversity, hospital or other
- Collaborators
- Reckitt Benckiser LLC
- Study start
- 1 Jul 2023 (actual)
- Primary completion
- 1 Jul 2024 (actual)
- Study completion
- 1 Jul 2024 (actual)
- First posted
- 21 Jul 2023 (actual)
- 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.
The goal of this mechanism of disease study is to investigate the effect of flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), on the cough hypersensitivity associated with upper respiratory tract infections (URTI).
The main questions it aims to answer are:
- Q1: Does a single treatment with an approved therapeutic dose of flurbiprofen, an NSAID that prevents the production of prostaglandins, acutely reduce objective measures of cough hypersensitivity in participants with URTI?
- Q2: Is the effect of flurbiprofen on cough hypersensitivity in URTI related to participant subjective ratings of acute cough severity?
- Q3: Is the effect of flurbiprofen on cough hypersensitivity in URTI related to the levels of prostaglandins or other inflammatory markers measurable in upper airway secretions?
Participants will be asked to undergo cough challenge testing, complete quality of life questionnaires, and have their nasal fluid, saliva and pharyngeal secretions sampled before and after a single treatment with flurbiprofen in the form of a lozenge or spray. Participants in the comparator arms of the study will instead receive a placebo lozenge or low dose flurbiprofen spray.
Detailed description
People with an Upper Respiratory Tract Infection (URTI), for example the common cold, often exhibit heightened sensitivity to stimuli that cause coughing. This heightened sensitivity is thought to contribute to the short-term excessive coughing that accompanies the infection. What causes the heightened sensitivity is not known but may involve inflammation in the throat.
HYPOTHESIS: The investigators hypothesise that in URTI prostaglandins may lead to cough hypersensitivity by either a direct or indirect action on cough nerve fibre endings in the larynx, lowering their activation threshold to cough stimuli.
OVERALL AIM: This study aims to investigate this hypothesis by assessing whether a single treatment with flurbiprofen, an existing over the counter anti-inflammatory drug (NSAID) medication contained in some 'cold and flu remedies' and used to relieve sore throat in URTI, reduces heightened cough sensitivity through a reduction in throat inflammation. The investigators will recruit 120 otherwise healthy male and female adults experiencing an URTI with acute cough for laboratory assessments lasting 5-6 hours.
OBJECTIVES: The primary objective is to assess whether flurbiprofen, in commercially available lozenge or spray formulations, reduces an individual's sensitivity to a cough evoking stimulus by assessing participant responsiveness to inhaled capsaicin. Capsaicin is the naturally occurring 'hot' component of chilli peppers and commonly used to investigate the cough reflex in humans.
The secondary objectives are to assess the effect of flurbiprofen on:
- subjective measures of cough and urge-to-cough using questionnaires that assess Patient Reported Outcomes (PROs); and, B. the levels of chemical mediators of inflammation present in nasal secretions and saliva, to investigate flurbiprofen's potential mechanism of action.
METHOD: The investigators will test the hypothesis by measuring in participants their cough thresholds, subjective experiences with cough and urge-to-cough, and levels of airway prostaglandins and other inflammatory mediators, before and after a single treatment of flurbiprofen, which blocks the production of prostaglandins.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
- Model description
- 120 participants will be randomised into four study arms, i.e. treatment with: 1. flurbiprofen lozenge 2. placebo lozenge 3. flurbiprofen spray 4. low dose flurbiprofen spray Regardless of which arm they are assigned to, each participant will undergo cough challenge testing to test cough sensitivity, fill out quality of life questionnaires, and have their nasal fluid, saliva and pharyngeal fluid sampled for inflammatory markers before and after the intervention.
| Arm | Type | Receives |
|---|---|---|
| Flurbiprofen Oral Lozenge | Experimental | Drug: Flurbiprofen Oral Lozenge30 participants will be asked to suck one (1) flurbiprofen 8.75 mg honey and lemon lozenge (tradename: Strepfen) until dissolved. |
| Placebo lozenge | Placebo comparator | Drug: Difflam30 participants will be asked to suck one (1) non-medicated Difflam Soothing Drops + Immune Support Honey \& Lemon flavour lozenge until dissolved. |
| Flurbiprofen 8.75 MG | Experimental | Drug: Flurbiprofen 8.75 MG30 participants will be asked to perform three (3) oral actuations (2.91 mg per actuation) of flurbiprofen 8.75mg spray. |
| Low dose flurbiprofen spray | Other | Drug: Flurbiprofen 8.75 MG30 participants will be asked to perform one (1) oral actuation of flurbiprofen 8.75 mg spray, equivalent to a 2.91mg dosage. This will serve a a low dose control as there is no placebo spray available. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- An onset of any 2 URTI symptoms in past 3-5 days, such as a sore throat, fever, coughing, coughing up phlegm, sneezing, and runny nose;
- A current cough or urge-to-cough rated at least 5 in severity and/or ranking cough as subject's most bothersome symptom on Cold Symptoms Questionnaire (CSQ);
- A feeling of sickness interfering with their daily life, rated as at least mildly;
- A cough consistent with acute cough - i.e., cough onset with URTI and not ongoing, chronic cough;
- Written informed consent and a willingness and ability to comply with the study protocol.
Key exclusion criteria (11 listed)
- A pre-existing chronic lung disease (asthma, COPD, chronic bronchitis etc), to exclude these as causes for cough;
- The use of inhaled or systemic steroids / broncho-active medication, ACE inhibitors, oral or inhaled antihistamines, opiates, gabapentin, tricyclic antidepressants (current or within the past 3 months), as these will alter airway inflammatory profiles and/ or cough sensitivity;
- A current cigarette or marijuana smoker/vaper, recreational drug user, or have given up smoking/vaping within the last 12 months, or a former smoker with greater than 20 pack-years, alter airway inflammatory profiles and/ or cough sensitivity;
- Pre-existing chronic cough (cough persisting for more than 8 weeks): unexplained chronic cough (UCC) or refractory chronic cough (RCC) associated with or without a pre-existing condition (GERD, rhinitis, etc), as we are studying acute cough;
- Prior experience of an allergic or bad reaction to capsaicin or chilli (which is rare);
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 |
|---|---|---|
| Flurbiprofen Oral LozengeAlso: Strepfen Intensive Lozenge - Honey and Lemon FlavourThis commercially available, over-the-counter lozenge manufactured by Reckitt Benckiser contains flurbiprofen as the active ingredient and is registered for the short-term treatment of sore throat associated with upper respiratory tract infections in people over the age of 12 years. | Drug | Flurbiprofen Oral Lozenge |
| DifflamAlso: Difflam Soothing Drops + Immune Support Honey & Lemon FlavourThis is a non-medicated, control lozenge that is the same flavour as the experimental lozenge that is marketed to help soothe dry, tickly throats while supporting the body's immune health. | Drug | Placebo lozenge |
| Flurbiprofen 8.75 MGAlso: Strepfen Intensive Oromucosal Spray; Strepsils Intensive Oromucosal SprayThis commercially available, over-the-counter spray manufactured by Reckitt Benckiser contains flurbiprofen as the active ingredient and is registered for the short-term treatment of sore throat associated with upper respiratory tract infections in people over the age of 12 years. It requires 3 actuations of the spray to deliver the full 8.75 dose. Here, a low dose control can be delivered by only performing 1 actuation of the spray. | Drug | Flurbiprofen 8.75 MG, Low dose flurbiprofen spray |
Primary outcome
Change in objective measures of cough sensitivity
Time frame: Cough challenge testing will be performed at baseline and 3 hours after intervention.
Participants' cough sensitivity thresholds will be measured by inhaled cough challenge testing. This involves participants inhaling single breaths of increasing concentrations of a tussigenic stimulus (capsaicin; (active component of hot chili peppers) as well as saline control to determine threshold doses that elicit an urge to cough, two coughs (C2) and five coughs (C5). The principal endpoint is measured as the change in capsaicin concentration needed to elicit cough responses and the unit of measure is micromolar.
5 secondary outcomes
Change in Cold Symptoms Questionnaire (CSQ) score
Time frame: Participant self-reports using the Cold Symptoms Questionnaire at baseline and every 30 min after invention until 3 hours has elapsed.
Change in levels of inflammatory markers in nasal fluid samples
Time frame: Nasal fluid samples will be taken at baseline and at 3 hours post-intervention.
Change in levels of inflammatory markers in saliva samples
Time frame: Saliva samples will be taken at baseline and at 3 hours post-intervention.
Change in levels of inflammatory markers in pharyngeal lavage samples
Time frame: Pharyngeal lavage samples will be taken at baseline and at 3 hours post-intervention.
Patients' Global Impression of Change score
Time frame: Participants self-report using the Patients' Global Impression of Change score at 3 hours post-intervention.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2024.
- Background: PubMed 30763726Mazzone SB, Farrell MJ. Heterogeneity of cough neurobiology: Clinical implications. Pulm Pharmacol Ther. 2019 Apr;55:62-66. doi: 10.1016/j.pupt.2019.02.002. Epub 2019 Feb 11.
- Background: PubMed 31100512Farrell MJ, Mazzone SB. Are neural pathways processing airway inputs sensitized in patients with cough hypersensitivity? Pulm Pharmacol Ther. 2019 Aug;57:101806. doi: 10.1016/j.pupt.2019.101806. Epub 2019 May 15.
- Background: PubMed 25383204Dicpinigaitis PV. Effect of viral upper respiratory tract infection on cough reflex sensitivity. J Thorac Dis. 2014 Oct;6(Suppl 7):S708-11. doi: 10.3978/j.issn.2072-1439.2013.12.02.
- Background: PubMed 28137663Driessen AK, McGovern AE, Narula M, Yang SK, Keller JA, Farrell MJ, Mazzone SB. Central mechanisms of airway sensation and cough hypersensitivity. Pulm Pharmacol Ther. 2017 Dec;47:9-15. doi: 10.1016/j.pupt.2017.01.010. Epub 2017 Jan 27.
- Background: PubMed 22890476Renner B, Mueller CA, Shephard A. Environmental and non-infectious factors in the aetiology of pharyngitis (sore throat). Inflamm Res. 2012 Oct;61(10):1041-52. doi: 10.1007/s00011-012-0540-9. Epub 2012 Aug 14.
- Background: PubMed 33029351Lambkin-Williams R, Mann A, Shephard A. Inhibition of viral and bacterial trigger-stimulated prostaglandin E2 by a throat lozenge containing flurbiprofen: An in vitro study using a human respiratory epithelial cell line. SAGE Open Med. 2020 Sep 24;8:2050312120960568. doi: 10.1177/2050312120960568. eCollection 2020.
- Background: PubMed 12011823Schachtel BP, Homan HD, Gibb IA, Christian J. Demonstration of dose response of flurbiprofen lozenges with the sore throat pain model. Clin Pharmacol Ther. 2002 May;71(5):375-80. doi: 10.1067/mcp.2002.124079.
- Background: PubMed 24231654Schachtel B, Aspley S, Shephard A, Shea T, Smith G, Sanner K, Savino L, Rezuke J, Schachtel E. Onset of action of a lozenge containing flurbiprofen 8.75 mg: a randomized, double-blind, placebo-controlled trial with a new method for measuring onset of analgesic activity. Pain. 2014 Feb;155(2):422-428. doi: 10.1016/j.pain.2013.11.001. Epub 2013 Nov 12.
- 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.
Stuart Mazzone, PhD principal investigator
University of Melbourne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Flurbiprofen Oral Lozenge, Difflam and Flurbiprofen 8.75 MG in people with Cough and Upper Respiratory Tract Infections, run by University of Melbourne at 1 site in Australia.
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 5 inclusion and 11 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: finished, as of the sponsor's last update on 6 Dec 2024. 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 Australia. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in objective measures of cough sensitivity (time frame: Cough challenge testing will be performed at baseline and 3 hours after intervention.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05955885, which also lists 8 linked publications.
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 6 Dec 2024.