Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Ibuprofen 250 mg / Acetaminophen 500 mg Comparing The Antipyretic Effects in Healthy Male Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02761980
Recruitment Status : Completed
First Posted : May 4, 2016
Results First Posted : December 7, 2018
Last Update Posted : December 7, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Fever
Interventions Drug: Ibuprofen 250 mg / Acetaminophen 500 mg
Drug: Ibuprofen 250 mg
Drug: Acetaminophen 500 mg
Drug: Placebo
Enrollment 290
Recruitment Details  
Pre-assignment Details In this study, participants were administered at least 1 test dose of reference standard endotoxin (RSE) intravenously, based on their body weight before randomization, to induce pyrexia in them.
Arm/Group Title Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Hide Arm/Group Description Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment. Participants received single oral dose of a fixed dose combination of ibuprofen 250 milligram (mg) and acetaminophen 500 mg tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment. Participants received single oral dose of ibuprofen 250 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment. Participants received single oral dose of acetaminophen 500 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Period Title: Overall Study
Started 29 87 87 87
Completed 25 80 81 81
Not Completed 4 7 6 6
Reason Not Completed
Adverse Event             4             6             5             6
Withdrawal by Subject             0             1             0             0
Other             0             0             1             0
Arm/Group Title Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg Total
Hide Arm/Group Description Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment. Participants received single oral dose of a fixed dose combination of ibuprofen 250 mg and acetaminophen 500 mg tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment. Participants received single oral dose of ibuprofen 250 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment. Participants received single oral dose of acetaminophen 500 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment. Total of all reporting groups
Overall Number of Baseline Participants 29 87 87 87 290
Hide Baseline Analysis Population Description
Safety analysis set included all participants who received study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants 87 participants 87 participants 87 participants 290 participants
28.8  (7.97) 33.4  (10.54) 32.3  (10.19) 32.6  (9.99) 32.4  (10.07)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 87 participants 87 participants 87 participants 290 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
29
 100.0%
87
 100.0%
87
 100.0%
87
 100.0%
290
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 87 participants 87 participants 87 participants 290 participants
Hispanic or Latino
2
   6.9%
4
   4.6%
4
   4.6%
3
   3.4%
13
   4.5%
Not Hispanic or Latino
27
  93.1%
83
  95.4%
83
  95.4%
84
  96.6%
277
  95.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 87 participants 87 participants 87 participants 290 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   6.9%
1
   1.1%
0
   0.0%
3
   3.4%
6
   2.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
  17.2%
10
  11.5%
20
  23.0%
12
  13.8%
47
  16.2%
White
21
  72.4%
72
  82.8%
65
  74.7%
69
  79.3%
227
  78.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   3.4%
4
   4.6%
2
   2.3%
3
   3.4%
10
   3.4%
1.Primary Outcome
Title Time Weighted Sum of Temperature Difference (WSTD) From 0 to 8 Hours
Hide Description WSTD 0-8 was defined as time-weighted sum of temperature differences over 8 hours, weighted by time elapsed between each 2 consecutive time points post treatment (10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110 minutes, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5 and 8 hours). Temperature difference was defined as baseline temperature (at 0 hour) minus the post-baseline temperature at each time point up to 8 hours (10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110 minutes, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5 and 8 hours).
Time Frame 0 to 8 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent to treat (mITT) population included all randomized participants who were dosed with the study medication and RSE per procedures specified in protocol post amendment 4 and had a baseline assessment. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Hide Arm/Group Description:
Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of a fixed dose combination of ibuprofen 250 mg and acetaminophen 500 mg tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of ibuprofen 250 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of acetaminophen 500 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Overall Number of Participants Analyzed 27 81 83 82
Mean (Standard Deviation)
Unit of Measure: degrees fahrenheit
9.28  (6.395) 12.54  (5.519) 11.09  (6.355) 12.39  (6.278)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg+Acetaminophen 500 mg
Comments Treatment difference and 95 percent (%) confidence interval (CI) were based on Least Square Mean (LSM) from analysis of covariance (ANCOVA) with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 3.14
Confidence Interval (2-Sided) 95%
1.13 to 5.15
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Ibuprofen 250 mg
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.210
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
-0.52 to 2.33
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Acetaminophen 500 mg
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.280
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
-0.64 to 2.21
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 2.23
Confidence Interval (2-Sided) 95%
0.22 to 4.25
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Acetaminophen 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 2.35
Confidence Interval (2-Sided) 95%
0.33 to 4.37
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg, Acetaminophen 500 mg
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.864
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-1.54 to 1.29
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Time Weighted Sum of Temperature Differences (WSTD) From Baseline Through Hours 2, 4 and 6
Hide Description WSTD 0-2, 0-4 and 0-6 was defined as time-weighted sum of temperature differences over each specified time interval (0-2 hour, 0-4 hour and 0-6 hour), weighted by time elapsed between each 2 consecutive time points post treatment (10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110 minutes, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6 hour), within each time interval. Temperature difference was defined as baseline temperature (at 0 hour) minus the post-baseline temperature at each time point within each specified time interval: 1) 0-2 hour (20, 30, 40, 50, 60, 70, 80, 90, 100, 110 minutes) , 2) 0-4 hour (10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110 minutes, 2, 2.5, 3, 3.5, 4 hour), 3) 0-6 hour (10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110 minutes, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6 hour).
Time Frame 0 to 2 hours postdose, 0 to 4 hours postdose, 0 to 6 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants who were dosed with the study medication and RSE per procedures specified in protocol post amendment 4 and had a baseline assessment. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Hide Arm/Group Description:
Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of a fixed dose combination of ibuprofen 250 mg and acetaminophen 500 mg tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of ibuprofen 250 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of acetaminophen 500 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Overall Number of Participants Analyzed 27 81 83 82
Mean (Standard Deviation)
Unit of Measure: degrees fahrenheit
WSTD 0-2 -0.42  (1.827) 0.48  (1.829) -0.19  (1.856) 0.21  (1.732)
WSTD 0-4 1.79  (3.443) 3.69  (3.152) 2.61  (3.345) 3.41  (3.173)
WSTD 0-6 5.26  (4.833) 7.95  (4.245) 6.65  (4.788) 7.65  (4.604)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg+Acetaminophen 500 mg
Comments WSTD 0-2 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.29 to 1.51
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Ibuprofen 250 mg
Comments WSTD 0-2 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.078
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
-0.04 to 0.82
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Acetaminophen 500 mg
Comments WSTD 0-2 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.172
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
-0.13 to 0.74
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg
Comments WSTD 0-2 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.098
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
-0.10 to 1.13
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Acetaminophen 500 mg
Comments WSTD 0-2 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.054
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
-0.01 to 1.21
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg, Acetaminophen 500 mg
Comments WSTD 0-2 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.692
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.52 to 0.34
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg+Acetaminophen 500 mg
Comments WSTD 0-4 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 1.87
Confidence Interval (2-Sided) 95%
0.86 to 2.88
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Ibuprofen 250 mg
Comments WSTD 0-4 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.094
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
-0.10 to 1.33
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Acetaminophen 500 mg
Comments WSTD 0-4 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.217
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
-0.27 to 1.17
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg
Comments WSTD 0-4 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.24 to 2.27
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Acetaminophen 500 mg
Comments WSTD 0-4 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
0.40 to 2.44
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg, Acetaminophen 500 mg
Comments WSTD 0-4 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.659
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.87 to 0.55
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg+Acetaminophen 500 mg
Comments WSTD 0-6 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 2.62
Confidence Interval (2-Sided) 95%
1.16 to 4.08
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Ibuprofen 250 mg
Comments WSTD 0-6 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.135
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
-0.25 to 1.82
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Acetaminophen 500 mg
Comments WSTD 0-6 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.186
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
-0.34 to 1.74
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg
Comments WSTD 0-6 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 1.83
Confidence Interval (2-Sided) 95%
0.37 to 3.29
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, Acetaminophen 500 mg
Comments WSTD 0-6 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 1.92
Confidence Interval (2-Sided) 95%
0.45 to 3.39
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg, Acetaminophen 500 mg
Comments WSTD 0-6 hours
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.865
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-1.12 to 0.94
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to Return to Normal Body Temperature
Hide Description Time to return to normal body temperature was defined as time from initial measurement of normal body temperature (at baseline; before administration of first test dose of RSE to induce pyrexia) till the time at which normal temperature was achieved again after pyrexia. Normal body temperature was defined as the last non-missing body temperature value, assessed prior to or at the time of first RSE test dose.
Time Frame Baseline (pre-dose) up to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants who were dosed with the study medication and RSE per procedures specified in protocol post amendment 4 and had a baseline assessment. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Hide Arm/Group Description:
Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of a fixed dose combination of ibuprofen 250 mg and acetaminophen 500 mg tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of ibuprofen 250 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of acetaminophen 500 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Overall Number of Participants Analyzed 27 81 83 82
Median (95% Confidence Interval)
Unit of Measure: minutes
360
(300 to 390)
330
(240 to 360)
390
(300 to 420)
330
(270 to 360)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg+Acetaminophen 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.449
Comments Generalized log-rank test based on interval-censored survival analysis using nonparametric survival method.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Ibuprofen 250 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.142
Comments Generalized log-rank test based on interval-censored survival analysis using nonparametric survival method.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Acetaminophen 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.822
Comments Generalized log-rank test based on interval-censored survival analysis using nonparametric survival method.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.671
Comments Generalized log-rank test based on interval-censored survival analysis using nonparametric survival method.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Acetaminophen 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.514
Comments Generalized log-rank test based on interval-censored survival analysis using nonparametric survival method.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg, Acetaminophen 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.191
Comments Generalized log-rank test based on interval-censored survival analysis using nonparametric survival method.
Method Log Rank
Comments [Not Specified]
4.Secondary Outcome
Title Time to Rescue Medication
Hide Description Time to rescue medication (other than study treatment) (in minutes) was defined as time from first dosing of study medication to the time a participant first takes a rescue medication, or to the end of the study time for participants that do not take any rescue medication prior to the end of the study. The rescue medication was defined as medication received for the treatment of fever during the time period from the administration of study medication to the time of end of the study.
Time Frame 0 to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants who were dosed with the study medication and RSE per procedures specified in protocol post amendment 4 and had a baseline assessment. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Hide Arm/Group Description:
Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of a fixed dose combination of ibuprofen 250 mg and acetaminophen 500 mg tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of ibuprofen 250 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of acetaminophen 500 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Overall Number of Participants Analyzed 27 81 83 82
Median (95% Confidence Interval)
Unit of Measure: minutes
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median, lower and upper limit of 95% CI was not estimable due to the low number of participants who had rescue medication.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Ibuprofen 250 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.997
Comments P-value, hazard ratio (HR) and corresponding 95% CI were calculated based on the proportional hazards (PH) model with treatment term in the model.
Method hazard ratio
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.998
Comments P-value, HR and corresponding 95% CI were calculated based on the PH model with treatment term in the model.
Method Hazard Ratio
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg, Acetaminophen 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.997
Comments P-value, HR and corresponding 95% CI were calculated based on the PH model with treatment term in the model.
Method Hazard Ratio
Comments [Not Specified]
5.Secondary Outcome
Title Time Weighted Sum of Temperature Difference From 6 to 8 Hours
Hide Description WSTD 6-8 was defined as time-weighted sum of temperature differences between 6 to 8 hours post-dose, weighted by time elapsed between each 2 consecutive time points within 6 to 8 hours (6.5, 7, 7.5 and 8 hours). Temperature difference was defined as temperature at 6 hours minus the temperature at specified time points (6.5, 7, 7.5 and 8 hours).
Time Frame 6 to 8 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants who were dosed with the study medication and RSE per procedures specified in protocol post amendment 4 and had a baseline assessment. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Hide Arm/Group Description:
Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of a fixed dose combination of ibuprofen 250 mg and acetaminophen 500 mg tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of ibuprofen 250 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of acetaminophen 500 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Overall Number of Participants Analyzed 27 81 83 82
Mean (Standard Deviation)
Unit of Measure: degrees fahrenheit
4.96  (2.228) 5.69  (1.904) 5.49  (2.261) 5.84  (2.328)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg+Acetaminophen 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.101
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
-0.13 to 1.48
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Ibuprofen 250 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.582
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-0.41 to 0.73
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg+Acetaminophen 500 mg, Acetaminophen 500 mg
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.614
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
-0.43 to 0.72
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Ibuprofen 250 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.212
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
-0.29 to 1.32
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Acetaminophen 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.202
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
-0.28 to 1.34
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ibuprofen 250 mg, Acetaminophen 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Treatment difference and 95 % CI were based on LSM from ANCOVA with treatment, and covariates time from the first RSE full dose to randomization, and baseline temperature.
Statistical Test of Hypothesis P-Value 0.965
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.58 to 0.55
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title Number of Participants With Treatment Emergent Adverse Events (AEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to 24 hours after discharge (up to 32 hours) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
Time Frame Baseline up to 24 hours after discharge (up to 32 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received study medication.
Arm/Group Title Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Hide Arm/Group Description:
Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of a fixed dose combination of ibuprofen 250 mg and acetaminophen 500 mg tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of ibuprofen 250 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Participants received single oral dose of acetaminophen 500 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
Overall Number of Participants Analyzed 29 87 87 87
Measure Type: Count of Participants
Unit of Measure: Participants
1
   3.4%
1
   1.1%
0
   0.0%
0
   0.0%
Time Frame Baseline up to 24 hours after discharge (up to 32 hours)
Adverse Event Reporting Description Safety analysis set included all participants who received study medication.
 
Arm/Group Title Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Hide Arm/Group Description Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment. Participants received single oral dose of a fixed dose combination of ibuprofen 250 mg and acetaminophen 500 mg tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment. Participants received single oral dose of ibuprofen 250 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment. Participants received single oral dose of acetaminophen 500 mg tablet during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.
All-Cause Mortality
Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)   0/87 (0.00%)   0/87 (0.00%)   0/87 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)   0/87 (0.00%)   0/87 (0.00%)   0/87 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Ibuprofen 250 mg+Acetaminophen 500 mg Ibuprofen 250 mg Acetaminophen 500 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/29 (3.45%)   1/87 (1.15%)   0/87 (0.00%)   0/87 (0.00%) 
Ear and labyrinth disorders         
Ear pain * 1  1/29 (3.45%)  0/87 (0.00%)  0/87 (0.00%)  0/87 (0.00%) 
Skin and subcutaneous tissue disorders         
Rash macular * 1  0/29 (0.00%)  1/87 (1.15%)  0/87 (0.00%)  0/87 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02761980     History of Changes
Other Study ID Numbers: B5061002
GEMINI IF ( Other Identifier: Alias Study Number )
First Submitted: May 2, 2016
First Posted: May 4, 2016
Results First Submitted: November 8, 2018
Results First Posted: December 7, 2018
Last Update Posted: December 7, 2018