Trial Outcomes & Findings for A Study of Ibuprofen 250 mg / Acetaminophen 500 mg Comparing The Antipyretic Effects in Healthy Male Volunteers (NCT NCT02761980)

NCT ID: NCT02761980

Last Updated: 2018-12-07

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

290 participants

Primary outcome timeframe

0 to 8 hours post-dose

Results posted on

2018-12-07

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.	Ibuprofen 250 mg+Acetaminophen 500 mg 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.	Ibuprofen 250 mg 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.	Acetaminophen 500 mg 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 Study STARTED	29	87	87	87
Overall Study COMPLETED	25	80	81	81
Overall Study NOT COMPLETED	4	7	6	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.	Ibuprofen 250 mg+Acetaminophen 500 mg 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.	Ibuprofen 250 mg 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.	Acetaminophen 500 mg 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 Study Adverse Event	4	6	5	6
Overall Study Withdrawal by Subject	0	1	0	0
Overall Study Other	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=29 Participants Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.	Ibuprofen 250 mg+Acetaminophen 500 mg n=87 Participants 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.	Ibuprofen 250 mg n=87 Participants 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.	Acetaminophen 500 mg n=87 Participants 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 n=290 Participants Total of all reporting groups
Age, Continuous	28.8 years STANDARD_DEVIATION 7.97 • n=5 Participants	33.4 years STANDARD_DEVIATION 10.54 • n=7 Participants	32.3 years STANDARD_DEVIATION 10.19 • n=5 Participants	32.6 years STANDARD_DEVIATION 9.99 • n=4 Participants	32.4 years STANDARD_DEVIATION 10.07 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	87 Participants n=7 Participants	87 Participants n=5 Participants	87 Participants n=4 Participants	290 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	13 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	83 Participants n=7 Participants	83 Participants n=5 Participants	84 Participants n=4 Participants	277 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants	12 Participants n=4 Participants	47 Participants n=21 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	72 Participants n=7 Participants	65 Participants n=5 Participants	69 Participants n=4 Participants	227 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants

PRIMARY outcome

Timeframe: 0 to 8 hours post-dose

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.	Ibuprofen 250 mg+Acetaminophen 500 mg n=81 Participants 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.	Ibuprofen 250 mg n=83 Participants 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.	Acetaminophen 500 mg n=82 Participants 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.
Time Weighted Sum of Temperature Difference (WSTD) From 0 to 8 Hours	9.28 degrees fahrenheit Standard Deviation 6.395	12.54 degrees fahrenheit Standard Deviation 5.519	11.09 degrees fahrenheit Standard Deviation 6.355	12.39 degrees fahrenheit Standard Deviation 6.278

SECONDARY outcome

Timeframe: 0 to 2 hours postdose, 0 to 4 hours postdose, 0 to 6 hours postdose

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.	Ibuprofen 250 mg+Acetaminophen 500 mg n=81 Participants 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.	Ibuprofen 250 mg n=83 Participants 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.	Acetaminophen 500 mg n=82 Participants 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.
Time Weighted Sum of Temperature Differences (WSTD) From Baseline Through Hours 2, 4 and 6 WSTD 0-2	-0.42 degrees fahrenheit Standard Deviation 1.827	0.48 degrees fahrenheit Standard Deviation 1.829	-0.19 degrees fahrenheit Standard Deviation 1.856	0.21 degrees fahrenheit Standard Deviation 1.732
Time Weighted Sum of Temperature Differences (WSTD) From Baseline Through Hours 2, 4 and 6 WSTD 0-4	1.79 degrees fahrenheit Standard Deviation 3.443	3.69 degrees fahrenheit Standard Deviation 3.152	2.61 degrees fahrenheit Standard Deviation 3.345	3.41 degrees fahrenheit Standard Deviation 3.173
Time Weighted Sum of Temperature Differences (WSTD) From Baseline Through Hours 2, 4 and 6 WSTD 0-6	5.26 degrees fahrenheit Standard Deviation 4.833	7.95 degrees fahrenheit Standard Deviation 4.245	6.65 degrees fahrenheit Standard Deviation 4.788	7.65 degrees fahrenheit Standard Deviation 4.604

SECONDARY outcome

Timeframe: Baseline (pre-dose) up to 8 hours post dose

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.	Ibuprofen 250 mg+Acetaminophen 500 mg n=81 Participants 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.	Ibuprofen 250 mg n=83 Participants 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.	Acetaminophen 500 mg n=82 Participants 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.
Time to Return to Normal Body Temperature	360 minutes Interval 300.0 to 390.0	330 minutes Interval 240.0 to 360.0	390 minutes Interval 300.0 to 420.0	330 minutes Interval 270.0 to 360.0

SECONDARY outcome

Timeframe: 0 to 8 hours post dose

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.	Ibuprofen 250 mg+Acetaminophen 500 mg n=81 Participants 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.	Ibuprofen 250 mg n=83 Participants 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.	Acetaminophen 500 mg n=82 Participants 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.
Time to Rescue Medication	NA minutes Median, lower and upper limit of 95% CI was not estimable due to the low number of participants who had rescue medication.	NA minutes Median, lower and upper limit of 95% CI was not estimable due to the low number of participants who had rescue medication.	NA minutes Median, lower and upper limit of 95% CI was not estimable due to the low number of participants who had rescue medication.	NA minutes Median, lower and upper limit of 95% CI was not estimable due to the low number of participants who had rescue medication.

SECONDARY outcome

Timeframe: 6 to 8 hours postdose

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).

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.	Ibuprofen 250 mg+Acetaminophen 500 mg n=81 Participants 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.	Ibuprofen 250 mg n=83 Participants 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.	Acetaminophen 500 mg n=82 Participants 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.
Time Weighted Sum of Temperature Difference From 6 to 8 Hours	4.96 degrees fahrenheit Standard Deviation 2.228	5.69 degrees fahrenheit Standard Deviation 1.904	5.49 degrees fahrenheit Standard Deviation 2.261	5.84 degrees fahrenheit Standard Deviation 2.328

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 24 hours after discharge (up to 32 hours)

Population: Safety analysis set included all participants who received study medication.

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.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.	Ibuprofen 250 mg+Acetaminophen 500 mg n=87 Participants 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.	Ibuprofen 250 mg n=87 Participants 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.	Acetaminophen 500 mg n=87 Participants 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.
Number of Participants With Treatment Emergent Adverse Events (AEs)	1 Participants	1 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Ibuprofen 250 mg+Acetaminophen 500 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Ibuprofen 250 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Acetaminophen 500 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=29 participants at risk Participants received placebo as single oral dose tablets during the treatment duration of 8 hours. Participants were discharged after completion of study treatment.	Ibuprofen 250 mg+Acetaminophen 500 mg n=87 participants at risk 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.	Ibuprofen 250 mg n=87 participants at risk 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.	Acetaminophen 500 mg n=87 participants at risk 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.
Ear and labyrinth disorders Ear pain	3.4% 1/29 • Baseline up to 24 hours after discharge (up to 32 hours) Safety analysis set included all participants who received study medication.	0.00% 0/87 • Baseline up to 24 hours after discharge (up to 32 hours) Safety analysis set included all participants who received study medication.	0.00% 0/87 • Baseline up to 24 hours after discharge (up to 32 hours) Safety analysis set included all participants who received study medication.	0.00% 0/87 • Baseline up to 24 hours after discharge (up to 32 hours) Safety analysis set included all participants who received study medication.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/29 • Baseline up to 24 hours after discharge (up to 32 hours) Safety analysis set included all participants who received study medication.	1.1% 1/87 • Baseline up to 24 hours after discharge (up to 32 hours) Safety analysis set included all participants who received study medication.	0.00% 0/87 • Baseline up to 24 hours after discharge (up to 32 hours) Safety analysis set included all participants who received study medication.	0.00% 0/87 • Baseline up to 24 hours after discharge (up to 32 hours) Safety analysis set included all participants who received study medication.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee 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.
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