Infection
Conditions
Keywords
Fever, antipyretic, uncomplicated acute viral infection, uncomplicated acute bacterial infections
Brief summary
This single-dose trial will evaluate the efficacy of a novel ibuprofen formulation compared to placebo in patients with a fever due to an uncomplicated acute infection.
Interventions
DRUGIbuprofen
Single dose of a novel ibuprofen formulation (equal to 400mg ibuprofen)
DRUGPlacebo
Single dose of a placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects diagnosed with a fever secondary to an uncomplicated acute viral or bacterial infection. * Oral temperature measurement from 100 to 104 degrees Fahrenheit. * Onset of fever 3 days or less. * Otherwise good health.
Exclusion criteria
* Fever secondary to a chronic underlying medical condition or serious infection. * Currently taking antibiotics or antivirals. * Currently taking any medication which may interfere with the assessment of fever. * Pregnancy or breast-feeding. * Any serious medical or psychiatric disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Sum of The Temperature Differences From Baseline Through Hour 6 (STEMPD 0-6) | 0 to 6 hours | STEMPD 0-6 was defined as time-weighted sum of temperature differences over 6 hours, weighted by the time elapsed between each 2 consecutive time points. Temperature difference was defined as baseline temperature minus post-baseline temperature at each time point, where positive value indicated improvement in body temperature. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | Baseline, 0.25, 0.5, 1, 2, 4, 6, 8 hours | Change from baseline in temperature was calculated as baseline temperature minus post-baseline temperature at each time point, where positive value indicated improvement in body temperature. |
| Time to Treatment Failure | 0 to 8 hours | Median time of dropping out of the participants from the study due to lack of efficacy or use of rescue medication, whichever comes first. |
| Time-weighted Sum of The Temperature Differences From Baseline Through Hour 4 and Hour 8 (STEMPD 0-4 and STEMPD 0-8) | 0 to 4, 0 to 8 hours | STEMPD 0-4 and STEMPD 0-8 were defined as the time-weighted sum of temperature differences over 4 hours and 8 hours, weighted by the time elapsed between each 2 consecutive time points. Temperature difference was defined as baseline temperature minus post-baseline temperature at each time point, where positive value indicated improvement in body temperature. |
| Global Assessment of Study Medication as an Antipyretic | 8 hours | Global assessment of study medication was performed at the 8-hours time point or immediately before taking rescue medication (if necessary). It was scored on a 5-point categorical scale where 0=poor, 1=fair, 2=good, 3=very good, and 4=excellent. |
| Rating of Study Medication Relative to Usual Medication | 8 hours | Rating of study medication was performed at the 8-hours time point or immediately before taking rescue medication (if necessary). It was scored on a 5-point categorical scale where 0=poor, 1=fair, 2=good, 3=very good, and 4=excellent. |
| Cumulative Percentage of Participants With Treatment Failure | 0.25, 0.5, 1, 2, 4, 6, 8 hours | Percentage of participants who withdrew from the study due to lack of efficacy or received rescue medication. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Single oral dose of 2 placebo tablets matched to ibuprofen sodium 256 mg tablet. | 7 |
| Ibuprofen Sodium Single oral dose of 2 ibuprofen sodium 256 mg tablets, equivalent to 400 mg ibuprofen. | 9 |
| Total | 16 |
Baseline characteristics
| Characteristic | Placebo | Ibuprofen Sodium | Total |
|---|---|---|---|
| Age Continuous | 31.4 years STANDARD_DEVIATION 15.3 | 37.3 years STANDARD_DEVIATION 17.9 | 34.8 years STANDARD_DEVIATION 16.5 |
| Body Temperature | 100.99 Degrees Fahrenheit STANDARD_DEVIATION 0.83 | 100.58 Degrees Fahrenheit STANDARD_DEVIATION 0.66 | 100.76 Degrees Fahrenheit STANDARD_DEVIATION 0.74 |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 7 | 3 / 9 |
| serious Total, serious adverse events | 0 / 7 | 0 / 9 |
Outcome results
Primary
Time-weighted Sum of The Temperature Differences From Baseline Through Hour 6 (STEMPD 0-6)
STEMPD 0-6 was defined as time-weighted sum of temperature differences over 6 hours, weighted by the time elapsed between each 2 consecutive time points. Temperature difference was defined as baseline temperature minus post-baseline temperature at each time point, where positive value indicated improvement in body temperature.
Time frame: 0 to 6 hours
Population: Intent-to-treat (ITT) population included all randomized participants who received study medication and provided a baseline temperature assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-weighted Sum of The Temperature Differences From Baseline Through Hour 6 (STEMPD 0-6) | 3.0 Degrees Fahrenheit | Standard Deviation 6.3 |
| Ibuprofen Sodium | Time-weighted Sum of The Temperature Differences From Baseline Through Hour 6 (STEMPD 0-6) | 10.8 Degrees Fahrenheit | Standard Deviation 4.9 |
Comparison: Treatment difference (Ibuprofen sodium-Placebo) and corresponding 95 percent (%) confidence interval (CI) were calculated based on Least-squares (LS) means from the Analysis of Variance (ANOVA) model.p-value: 0.22895% CI: [-7.94, 24.6]ANOVA
Secondary
Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8
Change from baseline in temperature was calculated as baseline temperature minus post-baseline temperature at each time point, where positive value indicated improvement in body temperature.
Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 6, 8 hours
Population: ITT population included all randomized participants who received study medication and provided a baseline temperature assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 1 hour | 0.3 Degrees Fahrenheit | Standard Deviation 0.7 |
| Placebo | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 4 hours | 0.3 Degrees Fahrenheit | Standard Deviation 1.5 |
| Placebo | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 0.5 hours | 0.5 Degrees Fahrenheit | Standard Deviation 0.4 |
| Placebo | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 6 hours | 0.7 Degrees Fahrenheit | Standard Deviation 1.5 |
| Placebo | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 2 hours | 0.8 Degrees Fahrenheit | Standard Deviation 1 |
| Placebo | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 8 hours | 1.3 Degrees Fahrenheit | Standard Deviation 1.7 |
| Placebo | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 0.25 hours | 0.4 Degrees Fahrenheit | Standard Deviation 0.4 |
| Ibuprofen Sodium | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 8 hours | 1.3 Degrees Fahrenheit | Standard Deviation 1.9 |
| Ibuprofen Sodium | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 0.25 hours | 0.4 Degrees Fahrenheit | Standard Deviation 0.3 |
| Ibuprofen Sodium | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 0.5 hours | 0.7 Degrees Fahrenheit | Standard Deviation 0.4 |
| Ibuprofen Sodium | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 1 hour | 1.2 Degrees Fahrenheit | Standard Deviation 0.7 |
| Ibuprofen Sodium | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 2 hours | 1.9 Degrees Fahrenheit | Standard Deviation 0.9 |
| Ibuprofen Sodium | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 4 hours | 2.0 Degrees Fahrenheit | Standard Deviation 0.9 |
| Ibuprofen Sodium | Change From Baseline in Temperature at Hours 0.25, 0.5, 1, 2, 4, 6 and 8 | 6 hours | 2.1 Degrees Fahrenheit | Standard Deviation 1.3 |
Comparison: 0.25 hours: Treatment difference (Ibuprofen sodium-Placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.57695% CI: [-0.84, 0.54]ANOVA
Comparison: 0.5 hours: Treatment difference (Ibuprofen sodium-Placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.50295% CI: [-0.5, 0.87]ANOVA
Comparison: 1 hour: Treatment difference (Ibuprofen sodium-Placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.11695% CI: [-0.51, 3.12]ANOVA
Comparison: 2 hours: Treatment difference (Ibuprofen sodium-Placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.16195% CI: [-0.98, 4.14]ANOVA
Comparison: 4 hours: Treatment difference (Ibuprofen sodium-Placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.21595% CI: [-1.66, 5.41]ANOVA
Comparison: 6 hours: Treatment difference (Ibuprofen sodium-Placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.38895% CI: [-2.18, 4.52]ANOVA
Comparison: 8 hours: Treatment difference (Ibuprofen sodium-Placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.84995% CI: [-3.98, 4.61]ANOVA
Secondary
Cumulative Percentage of Participants With Treatment Failure
Percentage of participants who withdrew from the study due to lack of efficacy or received rescue medication.
Time frame: 0.25, 0.5, 1, 2, 4, 6, 8 hours
Population: ITT population included all randomized participants who received study medication and provided a baseline temperature assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Percentage of Participants With Treatment Failure | 2 hours | 0.0 percentage of participants |
| Placebo | Cumulative Percentage of Participants With Treatment Failure | 4 hours | 0.0 percentage of participants |
| Placebo | Cumulative Percentage of Participants With Treatment Failure | 0.25 hours | 0.0 percentage of participants |
| Placebo | Cumulative Percentage of Participants With Treatment Failure | 0.5 hours | 0.0 percentage of participants |
| Placebo | Cumulative Percentage of Participants With Treatment Failure | 1 hour | 0.0 percentage of participants |
| Placebo | Cumulative Percentage of Participants With Treatment Failure | 6 hours | 0.0 percentage of participants |
| Placebo | Cumulative Percentage of Participants With Treatment Failure | 8 hours | 0.0 percentage of participants |
| Ibuprofen Sodium | Cumulative Percentage of Participants With Treatment Failure | 6 hours | 0.0 percentage of participants |
| Ibuprofen Sodium | Cumulative Percentage of Participants With Treatment Failure | 1 hour | 0.0 percentage of participants |
| Ibuprofen Sodium | Cumulative Percentage of Participants With Treatment Failure | 4 hours | 0.0 percentage of participants |
| Ibuprofen Sodium | Cumulative Percentage of Participants With Treatment Failure | 2 hours | 0.0 percentage of participants |
| Ibuprofen Sodium | Cumulative Percentage of Participants With Treatment Failure | 0.25 hours | 0.0 percentage of participants |
| Ibuprofen Sodium | Cumulative Percentage of Participants With Treatment Failure | 8 hours | 11.1 percentage of participants |
| Ibuprofen Sodium | Cumulative Percentage of Participants With Treatment Failure | 0.5 hours | 0.0 percentage of participants |
Comparison: 8 hours: Treatment difference (Ibuprofen sodium-Placebo) and its associated CI were calculated based on Cochran-Mantel-Haenszel (CMH) adjusted proportion and the corresponding standard errors.p-value: 0.37895% CI: [-10.67, 32.89]Cochran-Mantel-Haenszel
Secondary
Global Assessment of Study Medication as an Antipyretic
Global assessment of study medication was performed at the 8-hours time point or immediately before taking rescue medication (if necessary). It was scored on a 5-point categorical scale where 0=poor, 1=fair, 2=good, 3=very good, and 4=excellent.
Time frame: 8 hours
Population: ITT population included all randomized participants who received study medication and provided a baseline temperature assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Global Assessment of Study Medication as an Antipyretic | 1.8 units on a scale | Standard Deviation 1.5 |
| Ibuprofen Sodium | Global Assessment of Study Medication as an Antipyretic | 2.5 units on a scale | Standard Deviation 1.1 |
Comparison: Treatment difference (Ibuprofen sodium-Placebo) and the associated CI were calculated based on the weighted Gamma statistic.p-value: 0.32495% CI: [-0.3, 1.27]Cochran-Mantel-Haenszel
Secondary
Rating of Study Medication Relative to Usual Medication
Rating of study medication was performed at the 8-hours time point or immediately before taking rescue medication (if necessary). It was scored on a 5-point categorical scale where 0=poor, 1=fair, 2=good, 3=very good, and 4=excellent.
Time frame: 8 hours
Population: ITT population included all randomized participants who received study medication and provided a baseline temperature assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Rating of Study Medication Relative to Usual Medication | 1.5 units on a scale | Standard Deviation 1.4 |
| Ibuprofen Sodium | Rating of Study Medication Relative to Usual Medication | 2.4 units on a scale | Standard Deviation 1.1 |
Comparison: Treatment difference (Ibuprofen sodium-Placebo) and the associated CI were calculated based on the weighted Gamma statistic.p-value: 0.2195% CI: [-0.12, 1.18]Cochran-Mantel-Haenszel
Secondary
Time to Treatment Failure
Median time of dropping out of the participants from the study due to lack of efficacy or use of rescue medication, whichever comes first.
Time frame: 0 to 8 hours
Population: ITT population included all randomized participants who received study medication and provided a baseline temperature assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Treatment Failure | NA hours |
| Ibuprofen Sodium | Time to Treatment Failure | NA hours |
Secondary
Time-weighted Sum of The Temperature Differences From Baseline Through Hour 4 and Hour 8 (STEMPD 0-4 and STEMPD 0-8)
STEMPD 0-4 and STEMPD 0-8 were defined as the time-weighted sum of temperature differences over 4 hours and 8 hours, weighted by the time elapsed between each 2 consecutive time points. Temperature difference was defined as baseline temperature minus post-baseline temperature at each time point, where positive value indicated improvement in body temperature.
Time frame: 0 to 4, 0 to 8 hours
Population: ITT population included all randomized participants who received study medication and provided a baseline temperature assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time-weighted Sum of The Temperature Differences From Baseline Through Hour 4 and Hour 8 (STEMPD 0-4 and STEMPD 0-8) | STEMPD 0-4 | 1.7 Degrees Fahrenheit | Standard Deviation 3.9 |
| Placebo | Time-weighted Sum of The Temperature Differences From Baseline Through Hour 4 and Hour 8 (STEMPD 0-4 and STEMPD 0-8) | STEMPD 0-8 | 5.7 Degrees Fahrenheit | Standard Deviation 9.4 |
| Ibuprofen Sodium | Time-weighted Sum of The Temperature Differences From Baseline Through Hour 4 and Hour 8 (STEMPD 0-4 and STEMPD 0-8) | STEMPD 0-4 | 6.7 Degrees Fahrenheit | Standard Deviation 2.9 |
| Ibuprofen Sodium | Time-weighted Sum of The Temperature Differences From Baseline Through Hour 4 and Hour 8 (STEMPD 0-4 and STEMPD 0-8) | STEMPD 0-8 | 13.4 Degrees Fahrenheit | Standard Deviation 7.3 |
Comparison: STEMPD 0-4: Treatment difference (Ibuprofen sodium-Placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.17195% CI: [-3.99, 15.97]ANOVA
Comparison: STEMPD 0-8: Treatment difference (Ibuprofen sodium-Placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.35495% CI: [-14.78, 32.69]ANOVA