Trial Outcomes & Findings for Placebo-Controlled Onset-of-Action Study of Flurbiprofen Utilizing the Double-Stopwatch Method (NCT NCT01986361)
NCT ID: NCT01986361
Last Updated: 2017-09-28
Results Overview
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.
COMPLETED
PHASE3
122 participants
up to 3 hours post dose on Day 1
2017-09-28
Participant Flow
133 patients were screened and 122 enrolled. Participants were randomly assigned in a 5:1 ratio to receive either an 8.75 mg flurbiprofen lozenge or a vehicle lozenge (placebo).
Participant milestones
| Measure |
Flurbiprofen 8.75 mg Lozenge
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
Overall Study
STARTED
|
101
|
21
|
|
Overall Study
COMPLETED
|
101
|
21
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Placebo-Controlled Onset-of-Action Study of Flurbiprofen Utilizing the Double-Stopwatch Method
Baseline characteristics by cohort
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 Participants
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 Participants
A single placebo lozenge is sucked until fully dissolved.
|
Total
n=122 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
19.5 years
STANDARD_DEVIATION 2.02 • n=5 Participants
|
19.6 years
STANDARD_DEVIATION 1.36 • n=7 Participants
|
19.5 years
STANDARD_DEVIATION 1.92 • n=5 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
43 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic or Non-Latino
|
93 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
112 Participants
n=5 Participants
|
|
Primary Race
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Primary Race
Black or African American
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Primary Race
Multi-Racial
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Primary Race
White
|
94 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
113 Participants
n=5 Participants
|
|
Weight
|
154.09 pounds
STANDARD_DEVIATION 31.221 • n=5 Participants
|
154.19 pounds
STANDARD_DEVIATION 35.885 • n=7 Participants
|
154.11 pounds
STANDARD_DEVIATION 31.913 • n=5 Participants
|
|
Height
|
67.67 inches
STANDARD_DEVIATION 4.187 • n=5 Participants
|
66.90 inches
STANDARD_DEVIATION 3.697 • n=7 Participants
|
67.54 inches
STANDARD_DEVIATION 4.103 • n=5 Participants
|
|
Sore Throat Scale (STS) Score
|
7.4 units on a scale
STANDARD_DEVIATION 0.97 • n=5 Participants
|
7.3 units on a scale
STANDARD_DEVIATION 1.02 • n=7 Participants
|
7.4 units on a scale
STANDARD_DEVIATION 0.98 • n=5 Participants
|
|
Sore Throat Pain Intensity Scale (STPIS)
|
73.8 units on a scale
STANDARD_DEVIATION 9.78 • n=5 Participants
|
73.8 units on a scale
STANDARD_DEVIATION 9.64 • n=7 Participants
|
73.8 units on a scale
STANDARD_DEVIATION 9.71 • n=5 Participants
|
PRIMARY outcome
Timeframe: up to 3 hours post dose on Day 1Population: Intent to treat population
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.
Outcome measures
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 Participants
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 Participants
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
Kaplan-Meier Estimates for Time to Meaningful Pain Relief
|
42.917 minutes
Interval 36.367 to 49.383
|
NA minutes
Interval 47.567 to
Less than 50% achieved meaningful relief
|
SECONDARY outcome
Timeframe: up to 3 hours post dose on Day 1Population: Intent to treat
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.
Outcome measures
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 Participants
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 Participants
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
Kaplan-Meier Estimates for Time of First Perceived Pain Relief
|
10.867 minutes
Interval 7.633 to 14.283
|
19.317 minutes
Interval 4.783 to 30.333
|
SECONDARY outcome
Timeframe: up to 3 hours post dose on Day 1Population: Intent to treat
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.
Outcome measures
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 Participants
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 Participants
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
Kaplan-Meier Estimates for Time to First Perceived Pain Relief That Is Confirmed By Meaningful Pain Relief
|
13.200 minutes
Interval 8.633 to 16.567
|
NA minutes
Interval 6.633 to
Less than 50% achieved meaningful relief
|
SECONDARY outcome
Timeframe: up to 3 hours post dose on Day 1Population: Intent to treat
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.
Outcome measures
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 Participants
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 Participants
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
Kaplan-Meier Estimates for Time of First Indication of Sore Throat Relief as Measured By Any Reduction in the Sore Throat Scale (STS)
|
15.000 minutes
Interval 10.0 to 15.0
|
20.000 minutes
Interval 5.0 to 30.0
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose), up to 3 hours post dose on Day 1Population: Intent to treat
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.
Outcome measures
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 Participants
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 Participants
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
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)
|
15.000 minutes
Interval 10.0 to 20.0
|
NA minutes
Interval 10.0 to
Less than 50% achieved confirmed relief
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose), up to 3 hours post dose on Day 1Population: Intent to treat
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.
Outcome measures
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 Participants
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 Participants
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 5
|
-0.4 units on a scale
Standard Deviation 0.90
|
-0.4 units on a scale
Standard Deviation 0.67
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 10
|
-0.7 units on a scale
Standard Deviation 1.14
|
-0.6 units on a scale
Standard Deviation 0.98
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 15
|
-0.9 units on a scale
Standard Deviation 1.26
|
-0.6 units on a scale
Standard Deviation 0.87
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 20
|
-1.0 units on a scale
Standard Deviation 1.30
|
-0.6 units on a scale
Standard Deviation 0.74
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 25
|
-1.3 units on a scale
Standard Deviation 1.34
|
-0.7 units on a scale
Standard Deviation 0.90
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 30
|
-1.6 units on a scale
Standard Deviation 1.41
|
-1.0 units on a scale
Standard Deviation 1.12
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 35
|
-1.8 units on a scale
Standard Deviation 1.52
|
-1.0 units on a scale
Standard Deviation 1.20
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 40
|
-2.0 units on a scale
Standard Deviation 1.50
|
-1.1 units on a scale
Standard Deviation 1.34
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 45
|
-2.2 units on a scale
Standard Deviation 1.54
|
-1.2 units on a scale
Standard Deviation 1.36
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 50
|
-2.3 units on a scale
Standard Deviation 1.59
|
-1.3 units on a scale
Standard Deviation 1.52
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 55
|
-2.4 units on a scale
Standard Deviation 1.64
|
-1.1 units on a scale
Standard Deviation 1.49
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 60
|
-2.5 units on a scale
Standard Deviation 1.69
|
-1.1 units on a scale
Standard Deviation 1.65
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 70
|
-2.6 units on a scale
Standard Deviation 1.74
|
-1.2 units on a scale
Standard Deviation 1.72
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 80
|
-2.7 units on a scale
Standard Deviation 1.85
|
-1.1 units on a scale
Standard Deviation 1.61
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 90
|
-2.7 units on a scale
Standard Deviation 1.86
|
-1.0 units on a scale
Standard Deviation 1.77
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 100
|
-2.7 units on a scale
Standard Deviation 1.87
|
-1.0 units on a scale
Standard Deviation 1.72
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 110
|
-2.7 units on a scale
Standard Deviation 1.85
|
-1.0 units on a scale
Standard Deviation 1.83
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 120
|
-2.7 units on a scale
Standard Deviation 1.91
|
-1.0 units on a scale
Standard Deviation 1.94
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 130
|
-2.6 units on a scale
Standard Deviation 1.86
|
-1.0 units on a scale
Standard Deviation 1.83
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 140
|
-2.6 units on a scale
Standard Deviation 1.95
|
-0.9 units on a scale
Standard Deviation 1.82
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 150
|
-2.5 units on a scale
Standard Deviation 1.99
|
-0.8 units on a scale
Standard Deviation 1.97
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 160
|
-2.4 units on a scale
Standard Deviation 2.01
|
-0.9 units on a scale
Standard Deviation 2.06
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 170
|
-2.3 units on a scale
Standard Deviation 2.06
|
-0.8 units on a scale
Standard Deviation 2.23
|
|
Change From Baseline at Individual Timepoints in Sore Throat Scale (STS)
Minute 180
|
-2.3 units on a scale
Standard Deviation 2.05
|
-0.8 units on a scale
Standard Deviation 2.06
|
SECONDARY outcome
Timeframe: up to 3 hours post dose on Day 1Population: Intent to treat
Defined as the percentage of participants who pressed the second stopwatch during the 3 hour evaluation period.
Outcome measures
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 Participants
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 Participants
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
Percentage of Participants With Meaningful Pain Relief
|
78.2 percentage of participants
Interval 70.2 to 86.3
|
47.6 percentage of participants
Interval 26.3 to 69.0
|
SECONDARY outcome
Timeframe: up to 3 hours post dose on Day 1Population: Intent to treat
Defined as the percentage of participants who pressed the first stopwatch during the 3 hour evaluation period.
Outcome measures
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 Participants
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 Participants
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
Percentage of Participants With Perceived Pain Relief
|
97.0 percentage of participants
Interval 93.7 to 100.0
|
76.2 percentage of participants
Interval 58.0 to 94.4
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose), up to 3 hours post dose on Day 1Population: Intent to treat
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.
Outcome measures
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 Participants
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 Participants
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
Time Weighted Sum of Pain Intensity Differences (SPID) in Sore Throat Scale (STS) Over the 3 Hours Post-baseline (STS SPID3)
|
-403.9 units on a scale
Interval -457.3 to -350.5
|
-166.4 units on a scale
Interval -286.8 to -46.0
|
Adverse Events
Flurbiprofen 8.75 mg Lozenge
Placebo Lozenge
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Flurbiprofen 8.75 mg Lozenge
n=101 participants at risk
A single flurbiprofen lozenge is sucked until fully dissolved.
|
Placebo Lozenge
n=21 participants at risk
A single placebo lozenge is sucked until fully dissolved.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.99%
1/101 • up to 20 hours post dose
|
0.00%
0/21 • up to 20 hours post dose
|
|
Gastrointestinal disorders
Diarrhoea
|
0.99%
1/101 • up to 20 hours post dose
|
0.00%
0/21 • up to 20 hours post dose
|
|
Gastrointestinal disorders
Nausea
|
2.0%
2/101 • up to 20 hours post dose
|
0.00%
0/21 • up to 20 hours post dose
|
|
Nervous system disorders
Dizziness
|
0.99%
1/101 • up to 20 hours post dose
|
0.00%
0/21 • up to 20 hours post dose
|
|
Nervous system disorders
Headache
|
0.99%
1/101 • up to 20 hours post dose
|
4.8%
1/21 • up to 20 hours post dose
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.99%
1/101 • up to 20 hours post dose
|
0.00%
0/21 • up to 20 hours post dose
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.99%
1/101 • up to 20 hours post dose
|
0.00%
0/21 • up to 20 hours post dose
|
|
Respiratory, thoracic and mediastinal disorders
Tonsillar hypertrophy
|
0.99%
1/101 • up to 20 hours post dose
|
0.00%
0/21 • up to 20 hours post dose
|
|
General disorders
Pyrexia
|
2.0%
2/101 • up to 20 hours post dose
|
0.00%
0/21 • up to 20 hours post dose
|
|
Infections and infestations
Conjunctivitis infective
|
0.99%
1/101 • up to 20 hours post dose
|
0.00%
0/21 • up to 20 hours post dose
|
|
Infections and infestations
Laryngitis
|
0.99%
1/101 • up to 20 hours post dose
|
0.00%
0/21 • up to 20 hours post dose
|
Additional Information
Gail Solomon, Director, Clinical Development
Reckitt Benckiser Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER