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

Primary Purpose

Acute Pharyngitis, Sore Throat

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
flurbiprofen
placebo
Sponsored by
Reckitt Benckiser LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Pharyngitis focused on measuring Pharyngitis, Sore Throat, acute upper respiratory tract infection (URTI)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Connecticut - Student Health Services

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

flurbiprofen 8.75 mg lozenge

Placebo lozenge

Arm Description

A single flurbiprofen lozenge is sucked until fully dissolved.

A single placebo lozenge is sucked until fully dissolved.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
Percentage of Participants With Meaningful Pain Relief
Defined as the percentage of participants who pressed the second stopwatch during the 3 hour evaluation period.
Percentage of Participants With Perceived Pain Relief
Defined as the percentage of participants who pressed the first stopwatch during the 3 hour evaluation period.
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.

Full Information

First Posted
October 22, 2013
Last Updated
August 30, 2017
Sponsor
Reckitt Benckiser LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01986361
Brief Title
Placebo-Controlled Onset-of-Action Study of Flurbiprofen Utilizing the Double-Stopwatch Method
Official Title
A Single-Dose, Randomized, Double-Blind, Placebo-Controlled Onset-of-Action Study Utilizing the Double-Stopwatch Method
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Reckitt Benckiser LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Pharyngitis, Sore Throat
Keywords
Pharyngitis, Sore Throat, acute upper respiratory tract infection (URTI)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
122 (Actual)

8. Arms, Groups, and Interventions

Arm Title
flurbiprofen 8.75 mg lozenge
Arm Type
Experimental
Arm Description
A single flurbiprofen lozenge is sucked until fully dissolved.
Arm Title
Placebo lozenge
Arm Type
Placebo Comparator
Arm Description
A single placebo lozenge is sucked until fully dissolved.
Intervention Type
Drug
Intervention Name(s)
flurbiprofen
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Kaplan-Meier Estimates for Time to Meaningful Pain Relief
Description
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.
Time Frame
up to 3 hours post dose on Day 1
Secondary Outcome Measure Information:
Title
Kaplan-Meier Estimates for Time of First Perceived Pain Relief
Description
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.
Time Frame
up to 3 hours post dose on Day 1
Title
Kaplan-Meier Estimates for Time to First Perceived Pain Relief That Is Confirmed By Meaningful Pain Relief
Description
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.
Time Frame
up to 3 hours post dose on Day 1
Title
Kaplan-Meier Estimates for Time of First Indication of Sore Throat Relief as Measured By Any Reduction in the Sore Throat Scale (STS)
Description
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.
Time Frame
up to 3 hours post dose on Day 1
Title
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)
Description
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.
Time Frame
Baseline (Day 1, pre-dose), up to 3 hours post dose on Day 1
Title
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Description
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.
Time Frame
Baseline (Day 1, pre-dose), up to 3 hours post dose on Day 1
Title
Percentage of Participants With Meaningful Pain Relief
Description
Defined as the percentage of participants who pressed the second stopwatch during the 3 hour evaluation period.
Time Frame
up to 3 hours post dose on Day 1
Title
Percentage of Participants With Perceived Pain Relief
Description
Defined as the percentage of participants who pressed the first stopwatch during the 3 hour evaluation period.
Time Frame
up to 3 hours post dose on Day 1
Title
Time Weighted Sum of Pain Intensity Differences (SPID) in Sore Throat Scale (STS) Over the 3 Hours Post-baseline (STS SPID3)
Description
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.
Time Frame
Baseline (Day 1, pre-dose), up to 3 hours post dose on Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Shea, BS
Organizational Affiliation
Reckitt Benckiser Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Connecticut - Student Health Services
City
Storrs
State/Province
Connecticut
ZIP/Postal Code
06269-4011
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29381110
Citation
Schachtel B, Shephard A, Schachtel E, Lorton MB, Shea T, Aspley S. Qualities of Sore Throat Index (QuaSTI): measuring descriptors of sore throat in a randomized, placebo-controlled trial. Pain Manag. 2018 Mar;8(2):85-94. doi: 10.2217/pmt-2017-0041. Epub 2018 Jan 30.
Results Reference
derived

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

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