PMID- 34304913
OWN - NLM
STAT- MEDLINE
DCOM- 20211124
LR  - 20220531
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 43
IP  - 7
DP  - 2021 Jul
TI  - Efficacy of a Fixed-Dose Combination of Ibuprofen and Acetaminophen Compared With 
      Individual Monocomponents in Adult Male Subjects With Endotoxin-Induced Fever: A 
      Randomized Controlled Trial.
PG  - 1213-1227
LID - S0149-2918(21)00219-8 [pii]
LID - 10.1016/j.clinthera.2021.05.004 [doi]
AB  - PURPOSE: This study evaluated antipyretic efficacy and onset of a novel 
      fixed-dose combination (FDC) of ibuprofen (IBU; 250 mg) and acetaminophen (APAP; 
      500 mg) compared with placebo and IBU or APAP monocomponents. MET: This 
      single-center, randomized, double-blind, placebo-controlled, full-factorial study 
      was conducted in healthy males aged 18 to 55 years with pyrexia induced by 
      intravenous administration of reference standard endotoxin (RSE). After 
      attainment of an oral temperature >/=38.1 degrees C, subjects were randomized 3:3:3:1 to a 
      double-blind single oral dose of FDC IBU/APAP 250 mg/500 mg, APAP 500 mg, IBU 250 
      mg, or placebo. Oral temperature was measured every 10 minutes for 2 hours, then 
      every 30 minutes until 8 hours postdose. Time-weighted sum of temperature 
      differences from baseline to 8 hours (WSTD(0-8)) after study medication 
      administration was the primary efficacy end point. Secondary end points included 
      WSTD scores from 0 to 2 hours, 0 to 4 hours, 0 to 6 hours, and 6 to 8 hours; time 
      to return to "normal" temperature; time to rescue medication use; and global drug 
      evaluation. Safety was assessed via adverse events (AEs). FINDINGS: Two hundred 
      ninety subjects were randomized; 273 were included in the primary efficacy 
      analysis. WSTD(0-8) was significantly better for FDC IBU/APAP 250 mg/500 mg 
      (P = 0.002), IBU 250 mg (P = 0.030), and APAP 500 mg (P = 0.023) versus placebo; 
      there were no significant differences between active treatments. For WSTD(0-2), 
      only the FDC was statistically significant versus placebo (P = 0.004). All active 
      treatments were significantly better (P < 0.05) for WSTD(0-4) and WSTD(0-6) 
      versus placebo; there were no differences in WSTD(6-8) between cohorts. 
      Temperature returned to normal during the 8-hour treatment period in  approximately 50% of 
      subjects in each cohort. Only 1 subject (IBU cohort) took rescue medication. Post 
      hoc analyses at early time points revealed significant treatment differences 
      favoring FDC versus placebo and IBU for the WSTD from baseline during the 50- to 
      110-minute posttreatment window; for WSTD from baseline during the 80- to 
      110-minute posttreatment window, FDC provided significant treatment differences 
      versus placebo and both monocomponents. Overall, 223 (76.9%) of 290 subjects 
      experienced AEs related to RSE; only 2 subjects experienced treatment-related AEs 
      (FDC, rash; placebo, ear pain). IMPLICATIONS: Although the primary end point was 
      not met, these results suggest that FDC IBU/APAP 250 mg/500 mg provides effective 
      antipyresis with a faster onset versus equal doses of IBU and APAP alone. 
      ClinicalTrials.gov identifier: NCT02761980.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Smith, William
AU  - Smith W
AD  - Alliance for Multispecialty Research, The University of Tennessee Medical Center, 
      Knoxville, Tennessee. Electronic address: william.smith@amrllc.com.
FAU - Leyva, Rina
AU  - Leyva R
AD  - GSK Consumer Healthcare, Madison, New Jersey.
FAU - Kellstein, David
AU  - Kellstein D
AD  - Pfizer Consumer Healthcare, Madison, New Jersey.
FAU - Arthur, Edmund
AU  - Arthur E
AD  - Pfizer Inc, Peapack, New Jersey.
FAU - Cruz-Rivera, Mario
AU  - Cruz-Rivera M
AD  - Pfizer Consumer Healthcare, Madison, New Jersey.
LA  - eng
SI  - ClinicalTrials.gov/NCT02761980
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210723
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Endotoxins)
RN  - 362O9ITL9D (Acetaminophen)
RN  - WK2XYI10QM (Ibuprofen)
SB  - IM
MH  - *Acetaminophen/adverse effects
MH  - Adolescent
MH  - Adult
MH  - *Analgesics, Non-Narcotic/adverse effects
MH  - Double-Blind Method
MH  - Endotoxins
MH  - Humans
MH  - Ibuprofen/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Pain, Postoperative
MH  - Young Adult
OTO - NOTNLM
OT  - acetaminophen
OT  - antipyretic agent
OT  - endotoxin
OT  - fever
OT  - fixed-dose combination, ibuprofen
EDAT- 2021/07/27 06:00
MHDA- 2021/11/25 06:00
CRDT- 2021/07/26 05:34
PHST- 2020/07/17 00:00 [received]
PHST- 2021/04/28 00:00 [revised]
PHST- 2021/05/12 00:00 [accepted]
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2021/11/25 06:00 [medline]
PHST- 2021/07/26 05:34 [entrez]
AID - S0149-2918(21)00219-8 [pii]
AID - 10.1016/j.clinthera.2021.05.004 [doi]
PST - ppublish
SO  - Clin Ther. 2021 Jul;43(7):1213-1227. doi: 10.1016/j.clinthera.2021.05.004. Epub 
      2021 Jul 23.