A Study of Flurbiprofen 8.75 mg Lozenge in Patient With Pharyngitis

Study Overview
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Brief Summary
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The purposes of this study is to demonstrate the analgesic efficacy of flurbiprofen 8.75 mg lozenge compared to its vehicle lozenge and to demonstrate the safety of the flurbiprofen lozenge throughout the course of treating sore throat due to acute pharyngitis.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Multiple-Dose Study to Determine the Efficacy, Onset, and Duration of Action of Flurbiprofen 8.75 mg Lozenge Compared to Its Vehicle Control Lozenge in Patients With Painful Pharyngitis

Conditions
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Pharyngitis

Intervention / Treatment
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* Drug: Placebo
* Drug: Flurbiprofen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has a complaint of sore throat. 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. If the patient is a female of childbearing potential, the patient must have a negative urine pregnancy. The patient has provided written informed consent prior to any study-related procedures. Exclusion Criteria: The patient has a history of an upper gastrointestinal ulcer within the past 60 days, is currently experiencing clinically significant upper gastrointestinal complaints, or is currently taking medication regularly (≥ three times in the previous week). The patient has a history of any hepatic disease or renal dysfunction. The patient has a history of chronic analgesic use (≥ three times per week over the prior four weeks). (Patients on low-dose aspirin therapy may be allowed in the study per investigator's clinical decision.)

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>Participants sucked flurbiprofen 8.75mg lozenge every 3-6 hours up to 5 lozenges a day as needed for pain for 7 days. | Drug: Flurbiprofen<br>* Participants were instructed to suck one flurbiprofen 8.75 mg lozenge during the initial two-hour clinic visit. Upon discharge, participants were instructed to use study medication lozenge every 3-6 hours as needed for pain, up to a total of 5 study lozenges in 24 hours.<br>|
| Placebo Comparator: Placebo lozenge<br>Participants sucked vehicle placebo lozenge every 3-6 hours up to 5 lozenges a day as needed for pain for 7 days. | Drug: Placebo<br>* Participants were instructed to suck one placebo lozenge during the initial two-hour clinic visit. Upon discharge, participants were instructed to use study medication lozenge every 3-6 hours as needed for pain, up to a total of 5 study lozenges in 24 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Weighted Sum of Pain Intensity Differences (SPID) in Sore Throat Pain Intensity Scale (STPIS) Over the 24 Hours Post-baseline (STPIS SPID24) | STPIS measures sore throat pain intensity on a 100-mm visual analog scale completed by participants. A mark at 0-mm indicates no pain upon swallowing and 100-mm indicates severe pain. SPID24 was calculated as the sum of the time-weighted pain intensity differences from baseline until 24 hours. The full range was -114609 (complete pain relief within 2 minutes of dosing that lasts 24 hours) to 29191 (maximum pain within 2 minutes lasting 24 hours) using the mean baseline STPIS. Participants with a last recorded time point <21 hours were considered Not Evaluable. If a participant used rescue medication, all post-rescue STPIS values in the 24-hour interval were assigned the baseline value for STPIS. Missing scores of STPIS with non-missing STPIS scores at earlier and later assessments were imputed using linear interpolation assuming the time of the missing assessment to be the nominal time since initial dose. | baseline (pre-dose), 24 hours post-dose (every 2 minutes for one hour; every 10 minutes until hour 2; every 30 minutes until hour 6; and every hour the participant was awake between hours 7-24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Weighted Sum of Pain Intensity Differences (SPID) in Sore Throat Pain Intensity Scale (STPIS) Over the 2 Hours Post-baseline (STPIS SPID2) | STPIS measures sore throat pain intensity on a 100-mm visual analog scale completed by participants. A mark at 0-mm indicates no pain upon swallowing and 100-mm indicates severe pain. SPID2 was calculated as the sum of the time-weighted pain intensity differences from baseline until 2 hours post dosing. The full range was -9405 (complete pain relief within 2 minutes of dosing that lasts 2 hours) to 2395 (maximum pain within 2 minutes lasting 2 hours) using the mean baseline STPIS. If a participant used rescue medication (acetaminophen 650mg was allowed as needed post dose), all post-rescue STPIS values in the 24-hour interval were assigned the baseline value for STPIS. Missing scores of STPIS with non-missing STPIS scores at earlier and later assessments (recorded or derived due to rescue) were imputed using linear interpolation assuming the time of the missing assessment to be the nominal time since initial dose. | baseline (pre-dose), 2 hours post-dose (every 2 minutes for one hour; every 10 minutes until hour 2) | 
| Time Weighted Summed Differences in Difficulty Swallowing Scale (DSS) During the Initial 2 Hours From Baseline | Participants were asked to evaluate his/her difficulty swallowing (dysphagia) using a 100-mm visual analog scale at Baseline and 2 hours post dose. Participants were instructed to swallow and Place a line on the scale that best characterizes how difficult it is to swallow now. A mark at 0-mm indicated no difficulty and 100-mm indicated very difficult. Data is reported as the sum of the time-weighted pain intensity differences from baseline until 2 hours post dose. The full range was -9192 (no difficulty swallowing within 10 minutes of dosing that lasts 2 hours) to 2808 (maximum difficulty swallowing within 10 minutes lasting 2 hours) using the baseline DSS value. Missing values of DSS with non-missing values at assessments before and after were calculated using linear interpolation. | baseline (pre-dose), 2 hours post-dose (every 10 minutes until hour 2) | 
| Time Weighted Summed Differences in Difficulty Swallowing Scale (DSS) During the Initial 24 Hours From Baseline | Participants were asked to evaluate his/her difficulty swallowing (dysphagia) using a 100-mm visual analog scale at Baseline and until 24 hours post dose. Participants were instructed to swallow and Place a line on the scale that best characterizes how difficult it is to swallow now. A mark at 0-mm indicated no difficulty and 100-mm indicated very difficult. Data is reported as the sum of the time-weighted pain intensity differences from baseline until 24 hours post dose. The full range was -110304 (no difficulty swallowing within 10 minutes of dosing that lasts 24 hours) to 33696 (maximum difficulty swallowing within 10 minutes lasting 24 hours) using the baseline DSS value. Missing values of DSS with non-missing values at assessments before and after were calculated using linear interpolation. | baseline (pre-dose), 24 hours post-dose (every 10 minutes until hour 2, every 30 minutes until hour 6, hourly from 7-24 hours) | 
| Time Weighted Summed Differences in Swollen Throat Scale (SwoTS) During the Initial 2 Hours From Baseline | The participant was asked to evaluate how swollen his/her throat felt using a 100-mm visual analog scale at Baseline and at 1 hour, 70 minutes, 80 minutes, 90 minutes, 100 minutes, 110 minutes, and 2 hours. The patient was instructed to swallow and Place a line on the scale that best characterizes how swollen your throat feels now. A mark at 0-mm indicated not swollen and 100-mm indicated very swollen. The full range of the sum of the time-weighted swollen throat differences from baseline until 2 hours was -9336 (throat did not feel swollen at all within 1 hour of dosing and lasted 2 hours) to 2664 (maximum swollen throat reported within 1 hour and lasting 2 hours) using the mean baseline SwoTS. | baseline (pre-dose), 2 hours post-dose (at 1 hour, 70 minutes, 80 minutes, 90 minutes, 100 minutes, 110 minutes, and 2 hours) | 
| Time Weighted Summed Differences in Swollen Throat Scale (SwoTS) During the Initial 24 Hours From Baseline | The participant was asked to evaluate how swollen his/her throat felt using a 100-mm visual analog scale at Baseline and specified timeframes until 24 hours. The patient was instructed to swallow and Place a line on the scale that best characterizes how swollen your throat feels now. A mark at 0-mm indicated not swollen and 100-mm indicated very swollen. The full range of the sum of the time-weighted swollen throat differences from baseline until 24 hours was -112032 (throat did not feel swollen at all within 1 hour of dosing and lasted 24 hours) to 31968 (maximum swollen throat reported within 1 hour and lasting 24 hours) using the mean baseline SwoTS. | baseline (pre-dose), 24 hours post-dose (1 hour, 70 minutes, 80 minutes, 90 minutes, 100 minutes, 110 minutes, 2 hours, 2½ hours, 3 hours, 3½ hours, 4 hours, 4½ hours, 5 hours, 5½ hours, and 6 hours after the first dose, hourly from 7-24 hours) | 
| Change From Baseline at 24 Hours in the Tonsillo-Pharyngitis Assessment (TPA) Scores in Participants With Baseline TPA Scores >=8 | Tonsillo-Pharyngitis Assessment, or TPA, is an index of seven clinical features of the pain-producing condition itself, pharyngeal inflammation. The clinical features concern temperature, oropharyngeal color, size of tonsils, number of enanthems, largest size of cervical lymph node, number of lymph nodes, and maximum tenderness of lymph nodes. Each variable was rated on a scale of 0-3, with 0 representing the normal value, and 3 representing severe inflammation. The seven values are added together to create the TPA, ranging from 0-21. Negative change values represent improvement of symptoms. | Baseline (pre-dose), 24 hours post-dose | 
| Practitioner's Assessment of Pharyngeal Inflammation (P.A.I.N.) Scores at 24 Hours After Initial Dose | P.A.I.N is a four step scale in which physicians rate the severity of pharyngeal inflammation: No inflammation, mild, moderate and severe inflammation. | 24 hours post-dose | 
| Investigators' Clinical Assessment (CLIN) Of Study Medication as a Treatment for Sore Throat at 24 Hours After Initial Dose | Investigators assessed the effectiveness of study medication on the patient's sore throat at 24 hours following initial dose by answering the following question: Considering the patient's response to the study medicine over the past 24 hours, how do you rate the study medicine as a treatment for sore throat? Responses were poor, fair, good, very good or excellent. | 24 hours | 
| Participant Satisfaction Scores 24 Hours After Initial Dose | After 24 hours of treatment, participants rated their satisfaction with the treatment on a 7-step scale from extremely dissatisfied to extremely satisfied. | 24 hours | 
| Investigators' Clinical Assessment (CLIN) Of Study Medication as a Treatment for Sore Throat at the End of the Study (Day 7) | Investigators assessed the effectiveness of study medication on the patient's sore throat at the end of the study by answering the following question: Considering the patient's response to the study medicine over the past 7 days, how do you rate the study medicine as a treatment for sore throat? Responses were poor, fair, good, very good or excellent. | Day 7 | 
| Time Weighted Sum of Pain Intensity Differences (SPID) in Sore Throat Pain Intensity Scale Over 24 Hours Post-baseline (STPIS SPID24) For Participants With Baseline Practitioner's Assessment of Pharyngeal Inflammation (PAIN) of Moderate or Severe | STPIS measures sore throat pain intensity on a 100-mm visual analog scale completed by participants. A mark at 0-mm indicates no pain upon swallowing and 100-mm indicates severe pain. For the subgroup of patients with moderate/severe pharyngeal inflammation at baseline, SPID24 was calculated as the sum of the time weighted pain intensity differences from baseline until 24 hours. Taking inclusion criteria into account, the full range was -116196 (no pain at any post-dose time (0) - average baseline) to 27804 (maximum possible pain (100) - average baseline). Participants with their last recorded time point <21 hours were considered Not Evaluable. If a participant used rescue medication (acetaminophen 650mg was allowed as needed), all post-rescue STPIS values in the 24-hour interval were assigned the baseline value for STPIS. Missing scores of STPIS with non-missing STPIS scores at earlier and later assessments were imputed using linear interpolation. | baseline (pre-dose), 24 hours post-dose (every 2 minutes for one hour; every 10 minutes until hour 2; every 30 minutes until hour 6; and every hour the participant was awake between hours 7-24) | 
| Sore Throat Relief Rating Scale (STRRS) At 2 Hours After Initial Dose | Participants used a 6-category relief scale (no relief to complete relief) to grade the relief of his/her throat pain. The patient was instructed to swallow and: Considering how your throat felt before you took the study medicine, circle the phrase that best describes the relief of your sore throat now. | 2 hours | 
| Time Weighted Sum of Pain Intensity Differences (SPID) in Sore Throat Pain Intensity Scale (STPIS) at Each Post-Dose Time Point Until the Time Point at Which Comparison of the Arms Yielded a P-value <=0.05 | Data reported in summary form in Primary Outcome #1 are reported here at each post-dose timepoint until the comparison resulted in a P-value <=0.05 between the two treatment arms. STPIS was used to measure sore throat pain intensity using a 100-mm visual analog scale completed by participants that measures pain on swallowing (odynophagia). A mark at 0-mm indicates no pain and 100-mm indicates severe pain. The full range of the scale varies by timepoint due to the time weighting sum of SPID. The full scale at 40 minutes post dose was -3188 (complete pain relief within 2 minutes of dosing that lasts 40 minutes) to 812 (maximum pain within 2 minutes lasting 40 minutes) using the mean baseline STPIS. If a participant used rescue medication (acetaminophen 650mg was allowed as needed), all post-rescue STPIS values in the 24-hour interval were assigned the baseline value for STPIS. Missing scores of STPIS with non-missing STPIS scores at earlier and later assessments (rec | baseline (pre-dose), up to 23 hours post-dose (every 2 minutes for one hour; every 10 minutes until hour 2; every 30 minutes until hour 6; and every hour the participant was awake between hours 7-23) | 
| Kaplan-Meier Estimates for Sore Throat Pain Intensity Scale (STPIS) Time to Definite Improvement | As part of a protocol amendment, some participants defined a definite improvement level (DIL) relative to their actual pretreatment STPIS on the 100-mm visual analog scale. This was done after completing the 7 day trial. An alternative definition of STPIS time to onset of relief was the time from initial dose to the time the participant reaching DIL for at least 30 minutes. Data were censored if DIL was not achieved by 120 minutes following initial dose. Definite improvement must also occur prior to re-dosing or using rescue medication. | 2 hours | 
| Kaplan-Meier Estimates for Sore Throat Pain Intensity Scale (STPIS) Time to Definite Improvement Duration of Relief Using Participant-Defined Definite Improvement Levels (DIL) | As part of a protocol amendment, some participants defined a definite improvement level (DIL) relative to their actual pretreatment STPIS on the 100-mm visual analog scale. This was done after completing the 7 day trial. The time of first achieving DIL for 30 minutes within 6 hours (or until rescue or re-dosing) post-dosing will be determined. And the time falling below DIL within 6 hours will be determined. Duration is then defined as the time from first DIL until falling below DIL. Duration was set to zero if the STPIS score does not reach the DIL for at least 30 minutes for STPIS during the 6 hours. | 6 hours |