Placebo-Controlled Onset-of-Action Study of Flurbiprofen Utilizing the Double-Stopwatch Method

Study Overview
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Brief Summary
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The study's purpose is to demonstrate the onset of action, i.e., time to meaningful pain relief in patients with pharyngitis, of flurbiprofen 8.75 mg lozenge using the Double-Stopwatch Method (DSW).

Official Title
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A Single-Dose, Randomized, Double-Blind, Placebo-Controlled Onset-of-Action Study Utilizing the Double-Stopwatch Method

Conditions
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Acute Pharyngitis, Sore Throat

Intervention / Treatment
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* Drug: flurbiprofen
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary diagnosis: pharyngitis confirmed by a Tonsillo-Pharyngitis Assessment ≥ 5 Complaint of sore throat with an onset ≤ 4 days prior to randomization Have at least one symptom of upper respiratory tract infection (URTI) on the URTI Questionnaire (e.g., sore throat, runny nose, cough, fever) Have moderate or severe sore throat pain on the Throat Pain Scale Have a baseline Sore Throat Scale (STS) ≥ 6 If the patient is a female of childbearing potential, she has been using effective contraception since the last date of menses and is not breast-feeding or lactating. She is also willing to take adequate contraceptive precautions through 24 hours after the completion of the study. If the patient is a female of childbearing potential, the patient must have a negative urine pregnancy test (UPT) result (indicating not pregnant) obtained on the day of scheduled randomization, prior to the designated time of randomization The patient is willing to remain at the study centre for 3 hours after receiving the dose of study medication During the 3-hour evaluation of the study medication lozenge at the site, the patient is willing to take nothing by mouth (e.g., no smoking, food, candy, lozenges, chewing gum, liquids). Exclusion Criteria: Known allergy and/or hypersensitivity to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), or any other inactive ingredients such as honey, lemon flavor, menthol, or sucrose. History of an upper gastrointestinal ulcer within the past 60 days, current clinically significant upper gastrointestinal complaints, or current regular use (≥ 3 times in the previous week) of any medication for upper gastrointestinal symptoms, including antacids, H2 blockers, proton pump inhibitors or sucralfate History of any hepatic disease or renal dysfunction Other severe acute or chronic medical condition that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study. History of chronic analgesic use (≥ 3 times per week over the prior 4 weeks) Use of an antibiotic for an acute disease within the previous 24 hours before randomization. (Chronic antibiotic use, such as for acne, is acceptable.) Use of any quinolone antibiotic such as ciprofloxacin or nalidixic acid within the past week or concurrently is specifically prohibited. Use of mifepristone in the 12 days prior to the screening visit Use of inhaled therapy (e.g., inhaled steroids or β-agonists, such as Ventolin) on an acute basis for disease exacerbation in the week prior to the screening visit Use of any immediate release analgesic within 4 hours preceding administration of the study medication. Use of any sustained release analgesic within 12 hours preceding administration of the study medication. Use of any cold medication (i.e. decongestants, antihistamines, expectorants, antitussives) within 4 hours preceding administration of the dose of study medication. Use of any throat lozenge, throat spray, cough drop, or menthol-containing product within 2 hours preceding administration of the study medication Consumption of any caffeine-containing beverage (e.g., coffee, tea, hot chocolate, caffeinated soft drinks) within 5 minutes preceding administration of the study medication. Any evidence of mouth-breathing (which could worsen sore throat pain). Coughing that causes throat discomfort or any active physical disease (such as bronchopneumonia) which could compromise respiratory function and worsen a sore throat Unable in the opinion of the Investigator to comply fully with the study requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: flurbiprofen 8.75 mg lozenge<br>A single flurbiprofen lozenge is sucked until fully dissolved. | Drug: flurbiprofen<br>* A single flurbiprofen 8.75 mg lozenge which also contains 1 mg of menthol in its vehicle base for flavour and taste purposes (blinding). Lozenge is sucked until dissolved, and not chewed, bit or swallowed.<br>|
| Placebo Comparator: Placebo lozenge<br>A single placebo lozenge is sucked until fully dissolved. | Drug: placebo<br>* A single placebo lozenge which also contains 1 mg of menthol in its vehicle base for flavour and taste purposes (blinding). Lozenge is sucked until dissolved, and not chewed, bit or swallowed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Estimates for Time to Meaningful Pain Relief | Time to meaningful pain relief is a patient-reported outcome (PRO) captured as part of the double stopwatch method. Participants depress the second stop watch when they experience what they perceive as meaningful pain relief. Instructions to participants are: Stop the second stopwatch when the sore throat pain relief is meaningful to you. This does not mean you feel completely better, although you might, but when you feel relief of throat pain that is meaningful to you. Participants who did not have perceived pain relief were censored at 3 hours. | up to 3 hours post dose on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Estimates for Time of First Perceived Pain Relief | Time to first perceived pain relief is a patient-reported outcome (PRO) captured as part of the double stopwatch method. Participants depress the first stop watch when they experience any pain relief, termed perceived pain relief. Instructions to participants are: Stop the first stopwatch when you first feel any sore throat pain relief whatsoever. This does not mean you feel completely better, although you might, but when you first feel any relief of the throat pain you have now. Participants who did not have perceived pain relief were censored at 3 hours. | up to 3 hours post dose on Day 1 | 
| Kaplan-Meier Estimates for Time to First Perceived Pain Relief That Is Confirmed By Meaningful Pain Relief | Time to first perceived pain relief on the first stopwatch that was confirmed by meaningful pain relief on the second stopwatch. Participants who had no meaningful pain relief within 3 hours from baseline were censored to 3 hours. | up to 3 hours post dose on Day 1 | 
| Kaplan-Meier Estimates for Time of First Indication of Sore Throat Relief as Measured By Any Reduction in the Sore Throat Scale (STS) | Time to first indication of sore throat relief, defined as any reduction or decrease in STS observed during the 3 hours post dose. Participants who did not have any reduction in STS from baseline within 3 hours were censored to 3 hours. The participant was asked to evaluate his/her sore throat when swallowing using a vertical 0-10 Likert scale, where 0=not sore and 10=very sore. The participant was instructed: Circle the number that shows how sore your throat is now when you swallow. The STS was obtained at baseline, every 5 minutes after treatment during the first hour and every 10 minutes during the second and third hours. | up to 3 hours post dose on Day 1 | 
| Kaplan-Meier Estimates for Time of First Perceived Pain Reduction on the Sore Throat Scale (STS) Which is Followed by ≥ 20% Pain Reduction on the Sore Throat Pain Intensity Scale (STPIS) | Time to pain reduction on the STS (defined as any reduction or decrease observed during the 3 hours post dose) for participants whose improvement was confirmed by a >=20% reduction in pain on the STPIS. STS: The participant was asked to evaluate his/her sore throat when swallowing using a vertical 0-10 Likert scale, where 0=not sore and 10=very sore. The participant was instructed: Circle the number that shows how sore your throat is now when you swallow. The STS was obtained at baseline, every 5 minutes after treatment during the first hour and every 10 minutes during the second and third hours. STPIS: The participant was instructed to swallow and: Place a line on the Sore Throat Scale that best characterizes the severity of your sore throat now: 0mm=no pain and 100mm=severe pain. The STPIS was obtained at baseline, after the participant depressed the second stopwatch, and at 1, 2, and 3 hours postdose. | Baseline (Day 1, pre-dose), up to 3 hours post dose on Day 1 | 
| Change From Baseline at Individual Timepoints in Sore Throat Scale (STS) | The participant was asked to evaluate his/her sore throat when swallowing using a vertical 0-10 Likert scale, where 0=not sore and 10=very sore. The participant was instructed: Circle the number that shows how sore your throat is now when you swallow. The STS was obtained at baseline, every 5 minutes after treatment during the first hour and every 10 minutes during the second and third hours. | Baseline (Day 1, pre-dose), up to 3 hours post dose on Day 1 | 
| Percentage of Participants With Meaningful Pain Relief | Defined as the percentage of participants who pressed the second stopwatch during the 3 hour evaluation period. | up to 3 hours post dose on Day 1 | 
| Percentage of Participants With Perceived Pain Relief | Defined as the percentage of participants who pressed the first stopwatch during the 3 hour evaluation period. | up to 3 hours post dose on Day 1 | 
| Time Weighted Sum of Pain Intensity Differences (SPID) in Sore Throat Scale (STS) Over the 3 Hours Post-baseline (STS SPID3) | The participant was asked to evaluate his/her sore throat when swallowing using a vertical 0-10 Likert scale, where 0=not sore and 10=very sore. The participant was instructed: Circle the number that shows how sore your throat is now when you swallow. STS was obtained at baseline, every 5 minutes after treatment during the first hour and every 10 minutes during the second and third hours, for a total of 24 post-dose measurements. The time-weighted SPID combines relief magnitude (PID = change from baseline) as weighted by duration interval between ratings. SPID3 refers to measurements taken up to 3 hours post-baseline, and has a full range of -1332 (complete pain relief within 5 minutes of dosing that lasts for 3 hours) to 468 (drug escalates level of pain to a score of 10 and the pain stays at that level for 3 hours) using the mean baseline STS value 7.4 for this study. | Baseline (Day 1, pre-dose), up to 3 hours post dose on Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharyngitis, Sore Throat, acute upper respiratory tract infection (URTI)