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Trial registered on ANZCTR


Registration number
ACTRN12612000457842
Ethics application status
Approved
Date submitted
17/04/2012
Date registered
24/04/2012
Date last updated
4/12/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of flurbiprofen spray to reduce throat soreness in patients with upper respiratory tract infection.
Scientific title
A multi-centre, randomised, double-blinded, placebo-controlled, parallel group, multiple dose, study of the effectiveness of 8.75 mg flurbiprofen spray on the severity of throat soreness in patients with sore throat due to upper respiratory tract infection.
Secondary ID [1] 280347 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sore throat due to upper respiratory tract infection. 286307 0
Condition category
Condition code
Respiratory 286550 286550 0 0
Other respiratory disorders / diseases
Infection 286585 286585 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention: Flurbiprofen spray formulation, containing flurbiprofen 8.75 mg /540 microlitres (3 sprays aimed towards the back of the mouth equal 1 dose). Eligible participants will receive their first dose of randomised treatment in the clinic. They should not take their second dose until 6 hours later. Subsequent doses should be taken every 3-6 hours; up to a maximum of 5 doses per day. Participants will continue to take trial medication until their sore throat resolves or the end of Day 3 of study treatment, whichever occurs first.

Rescue Medication: paracetamol 500 mg tablets. Only if required, one to two tablets orally every four hours (to a maximum of eight tablets in 24 hours). Not to be take for more than three days.
Intervention code [1] 284711 0
Treatment: Drugs
Comparator / control treatment
Control: Placebo spray formulation (3 sprays aimed towards the back of the mouth equal 1 dose). Eligible participants will receive their first dose of randomised treatment (3 sprays aimed towards the back of the mouth equal 1 dose) in the clinic. They should not take their second dose until 6 hours later. Subsequent doses should be taken every 3-6 hours; up to a maximum of 5 doses per day. Participants will continue to take trial medication until their sore throat resolves or the end of Day 3 of study treatment, whichever occurs first.

Rescue Medication: paracetamol 500 mg tablets. Only if required, one to two tablets orally every four hours (to a maximum of eight tablets in 24 hours). Not to be take for more than three days.
Control group
Placebo

Outcomes
Primary outcome [1] 286981 0
Severity of throat soreness, assessed via the area under the change from baseline curve (AUC).
Throat soreness will be assessed using a 11-point ordinal scale (0-not sore, 10-very sore).
Timepoint [1] 286981 0
The 11-point ordinal scale for throat soreness will be assessed at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes (0-2 hours) after the first dose of study medication.
Secondary outcome [1] 297109 0
Throat soreness over 3 and 6 hours, assessed via the area under the change from baseline curve (AUC). Throat soreness will be assessed using a 11-point ordinal scale (0-not sore, 10-very sore).
Timepoint [1] 297109 0
The 11-point ordinal scale for throat soreness will be assessed at 120, 150, 180, 240, 300 and 360 minutes (3-6 hours) after the first dose of study medication.
Secondary outcome [2] 297111 0
Sore Throat Pain Intensity, assessed using the 100-mm VAS sore throat pain intensity scale
Timepoint [2] 297111 0
This will be assessed at 20, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 240, 300 and 360 minutes after the first dose of study medication.
Secondary outcome [3] 297112 0
Change from baseline in Sore Throat Pain Intensity, assessed using the 100-mm VAS sore throat pain intensity scale
Timepoint [3] 297112 0
At 20, 30, 45, 60, 75, 90, 105,120,135,150, 165, 180, 240, 300 and 360 minutes post first dose
Secondary outcome [4] 297113 0
Sore Throat Relief, assessed via the AUC of Total sum of pain relief ratings
Timepoint [4] 297113 0
At 2 hours, 3 hours and 6 hours post first dose
Secondary outcome [5] 297114 0
Sore Throat Relief, assessed via the total sum of pain relief ratings
Timepoint [5] 297114 0
At 20, 30, 45, 60, 75, 90, 105, 120, 150, 180, 240, 300 and 360 minutes post first dose
Secondary outcome [6] 297115 0
Difficulty swallowing over 2, 3 and 6 hours, assessed via the area under the change from baseline curve (AUC) using the 100-mm VAS difficulty swallowing scale.
Timepoint [6] 297115 0
This will be assessed at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105 and 120, 150, 180, 240, 300 and 360 minutes after the first dose of study medication. From 0 to 2, 0 to 3 and 0 to 6 hours
Secondary outcome [7] 297116 0
Change from baseline in difficulty swallowing, assessed via the 100mm VAS difficulty swallowing scale
Timepoint [7] 297116 0
At 5, 10, 15, 20, 30, 45, 60, 75, 90, 105 and 120, 150, 180, 240, 300 and 360 minutes post first dose
Secondary outcome [8] 297117 0
Swollen throat over 2, 3 and 6 hours, assessed via the area under the change from baseline curve (AUC) using the 100-mm VAS swollen throat scale.
Timepoint [8] 297117 0
This will be assessed at 30, 45, 60, 75, 90, 105,120,135,150, 165, 180, 240, 300 and 360 minutes after the first dose of study medication. From 0 to 2, 0 to 3 and 0 to 6 hours
Secondary outcome [9] 297118 0
Change from baseline in swollen throat scale, assessed via the 100mm VAS swollen throat scale
Timepoint [9] 297118 0
At 30, 45, 60, 75, 90, 105,120,135,150, 165, 180, 240, 300 and 360 minutes post first dose.
Secondary outcome [10] 297119 0
Throat Pain, assessed via the change from baseline in Throat Pain Scale (TPS) (using 4 point categorical scale)
Timepoint [10] 297119 0
At 2, 3 and 6 hours and final visit
Secondary outcome [11] 297120 0
Change from baseline in severity of throat soreness. Throat soreness will be assessed using a 11-point ordinal scale (0-not sore, 10-very sore).
Timepoint [11] 297120 0
At the end of Day 1, at 24 hours post first dose, and at the end of Days 2 and 3
Secondary outcome [12] 297121 0
Whether patient is symptom free. Freedom from symptoms is defined as the patient giving a sore throat score of 0 or 1 on the 11-point ordinal scale.
Timepoint [12] 297121 0
At the end of Day 1, at 24 hours post first dose and at the end of Days 2 and 3
Secondary outcome [13] 297122 0
Sore throat relief assessed using a 7-point categorical
scale (no relief, slight relief, mild relief, moderate relief, considerable relief, almost complete relief, complete relief)
Timepoint [13] 297122 0
At the ends of Day 1, at 24 hours post first dose, and at the end of Days 2 and 3
Secondary outcome [14] 297123 0
Change from baseline in Sore throat pain intensity using a Visual Analogue Scale (VAS).
Timepoint [14] 297123 0
At the end of Day 1, at 24 hours post first dose, and at the end of Days 2 and 3
Secondary outcome [15] 297124 0
Change from baseline in difficulty in swallowing using a Visual Analogue Scale (VAS).
Timepoint [15] 297124 0
At the end of Day 1, at 24 hours post first dose, and at the end of Days 2 and 3
Secondary outcome [16] 297125 0
Change from baseline in swollen throat using a Visual Analogue Scale (VAS).
Timepoint [16] 297125 0
At the end of Day 1, at 24 hours post first dose, and at the end of Days 2 and 3
Secondary outcome [17] 297126 0
Change in severity of throat soreness (using 11-point ordinal scale), sore throat relief (using a 7 point rating scale), difficulty swallowing, swollen throat and sore throat pain intensity using using Visual Analogue Scales (VAS).
Timepoint [17] 297126 0
From pre-spray to 2 hours post spray

Eligibility
Key inclusion criteria
- primary diagnosis: sore throat of onset within the past 4 days due to upper respiratory tract infection (URTI).
- sore throat (greater than or equal to 6) on the Throat Soreness Scale at baseline.
- objective findings confirm the presence of tonsillopharyngitis (greater than or equal to 5 points on the expanded 21-point Tonsillopharyngitis Assessment).
- must have greater than or equal to 50 mm on the Difficulty Swallowing Scale at Baseline
- must have greater than or equal to 33 mm on the Swollen Throat Scale at Baseline.
- written informed consent.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
People with any of the following are unable to participate in the study:
1. previous history of allergy or known intolerance to the study drug or the following formulation constituents: xylitol, mannitol, carbomer 974P, sodium bicarbonate, mint, peppermint, aspartame, citric acid, silicon dioxide; or paracetamol or any excipients in the Paracetamol formulation; or aspirin or NSAID’s
2. sore throat present for more than 4 days.
3. evidence of mouth breathing or severe coughing.
4. gastric sensitivity to NSAID’s or a history of gastrointestinal bleeding or perforation, severe colitis, haemorrhagic or haematopoietic disorders related to previous NSAID therapy
5. active or history of recurrent peptic ulcer/haemorrhage or intestinal ulceration.
6. existing stomach ulcers or a history of stomach ulcers.
7. history of bronchospasm, rhinitis or urticaria associated with aspirin or NSAID’s.
8. uncontrolled asthma and those who have had an asthma attack in the last 8 weeks.
9. uncontrolled hypertension or severe heart failure.
10. systemic lupus erythmatosus or mixed connective tissue disease.
11. potential for abnormal bleeding.
12. any disease that can compromise breathing e.g. bronchopneumonia.
13. those who have:
- taken any medicated confectionary, throat pastille, spray, or any product with demulcent properties such as boiled sweets in the previous 2 hours.
- used any sore throat medication containing a local anaesthetic within the previous 4 hours.
- used any analgesic, antipyretic or cold medication (e.g. decongestant, antihistamine, antitussive or throat lozenge) within the previous 8 hours.
- used a longer acting or slow release analgesic during the previous 24 hours e.g. Piroxicam and Naproxen.
- taken antibiotics during the previous 14 days
- taken carbamezepine, phenobarbitone, phenytoin, primidone, rifampicin, St Johns Wort or other drugs that induce liver enzymes in the 14 days before enrolment into the study (i.e. before first dosing day).
14. those taking:
- NSAIDs including cyclooxygenase-2 selective inhibitors
- warfarin and other coumarins
15. any painful condition that may distract attention from sore throat pain e.g. mouth ulcers etc.
16. history of severe renal or hepatic impairment; or alcohol abuse or state that they regularly consume alcohol in excess of the recommended amounts (excessive alcohol >21 units per week for females and >28 units per week for males.).
17. are glutathione-deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
18. any painful condition that requires analgesic usage.
19. unable to refrain from smoking during their stay in the 20. women of childbearing potential, who are pregnant or lactating, seeking pregnancy or failing to take adequate contraceptive precautions, (i.e. an oral or injectable contraceptive, an approved hormonal implant or topical patch or an intrauterine device).
21. previously randomised into the study; or have participated in a clinical trial in the previous 30 days.
22. unable in the opinion of the investigator to comply fully with the study requirements, e.g. such as those who cannot comprehend or correctly use thepain rating scales.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be recruited directly by presenting to their general practitioner (GP) when seeking treatment for their sore throat. Patients will also be recruited into the trial by referrals from pharmacies local to the GP practices and by responding directly to advertising.
Patients who consent to take part in the study will be allocated a unique subject number in numerical sequence. Issue of the study drug in this sequence will ensure randomisation.
After screening, eligible patients who meet the inclusion and exclusion criteria will be randomised to 1 of 2 blinded treatments, flurbiprofen spray or placebo spray.
Reckitt Benckiser (RB Investigational Material Supply Unit (IMSU) will hold the master code for the randomisation schedule and will supply the Investigator with the randomisation code for each patient as a sealed envelope.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Matching drug supplies will be randomised by RB IMSU, according to a computer-produced randomisation schedule.

The randomisation schedule will be checked by a statistician not involved in the analysis of the study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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 postcode(s) [1] 5246 0
5000
Recruitment postcode(s) [2] 5247 0
2031
Recruitment postcode(s) [3] 5248 0
2040
Recruitment postcode(s) [4] 5249 0
2522
Recruitment postcode(s) [5] 5250 0
2292
Recruitment postcode(s) [6] 5251 0
2010
Recruitment postcode(s) [7] 5252 0
4066
Recruitment postcode(s) [8] 5253 0
4075
Recruitment outside Australia
Country [1] 4264 0
New Zealand
State/province [1] 4264 0
Christchurch
Country [2] 4265 0
New Zealand
State/province [2] 4265 0
Auckland

Funding & Sponsors
Funding source category [1] 285120 0
Commercial sector/Industry
Name [1] 285120 0
Reckitt Benckiser Healthcare, UK Ltd
Address [1] 285120 0
Dansom Lane, Hull HU8 7DS, UK
Country [1] 285120 0
United Kingdom
Primary sponsor type
Commercial sector/Industry
Name
Novotech (Australia) Pty Limited
Address
Level 3, 235 Pyrmont Street
Pyrmont NSW 2009
Country
Australia
Secondary sponsor category [1] 283987 0
None
Name [1] 283987 0
Address [1] 283987 0
Country [1] 283987 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287139 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 287139 0
229 Greenhill Rd, Dulwich SA 5065
Ethics committee country [1] 287139 0
Australia
Date submitted for ethics approval [1] 287139 0
21/03/2012
Approval date [1] 287139 0
19/04/2012
Ethics approval number [1] 287139 0
2012-03-706
Ethics committee name [2] 287458 0
Uniting Care Health HREC
Ethics committee address [2] 287458 0
Top Floor Moorlands House, The Wesley Hospital, 451 Coronation Drive, Auchenflower, QLD 2066
Ethics committee country [2] 287458 0
Australia
Date submitted for ethics approval [2] 287458 0
23/03/2012
Approval date [2] 287458 0
04/05/2012
Ethics approval number [2] 287458 0
1209

Summary
Brief summary
The primary purpose of this study is to assess the effectiveness of a flurbiprofen spray formulation, over a period of three days, in relieving the symptoms of sore throat due to an upper respiratory tract infection. Flurbiprofen lozenges are approved by the Australian government’s health authority, the Therapeutic Goods Administration (TGA) for the relief of pain, swelling and inflammation due to severe sore throat. In this study, a spray formulation of flurbiprofen will be tested to determine if it too is effective in the relief of sore throat.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34079 0
Address 34079 0
Country 34079 0
Phone 34079 0
Fax 34079 0
Email 34079 0
Contact person for public queries
Name 17326 0
Zuhaib Baig
Address 17326 0
Reckitt Benckiser Healthcare
Dansom Lane, Hull, HU8 7DS UK
Country 17326 0
United Kingdom
Phone 17326 0
+44 (0) 1482 582675
Fax 17326 0
+44 (0) 1482 582172
Email 17326 0
Zuhaib.baig@rb.com
Contact person for scientific queries
Name 8254 0
Dr Phillip Berry
Address 8254 0
Reckitt Benckiser Healthcare
Dansom Lane, Hull, HU8 7DS UK
Country 8254 0
United Kingdom
Phone 8254 0
+44 (0) 1482 582675
Fax 8254 0
+44 (0) 1482 582172
Email 8254 0
Phillip.Berry@rb.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary