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

A Phase 3, Double-blind, Randomized, Placebo-controlled, Full Factorial, Safety And Efficacy Study Comparing The Antipyretic Effects Of A Single Oral Dose Of Ibuprofen (Ibu) 250 Mg/ Acetaminophen (Apap) 500 Mg Caplets To Ibu 250 Mg And Apap 500 Mg Caplets In Healthy Male Volunteers With Fever Induced By An Endotoxin

This is a single dose study that will evaluate the efficacy and safety of a Fixed Dose Combination Ibuprofen 250 mg/ Acetaminophen 500 mg tablet in healthy male patients with fever. Results for the Fixed Dose Combination product will be compared to the individual components Ibuprofen 250 mg and Acetaminophen 500 mg and also compared to placebo.

Study Overview

• Status: Completed
• Conditions: Fever
• Intervention / Treatment: Drug: Placebo; Drug: Ibuprofen 250 mg / Acetaminophen 500 mg; Drug: Ibuprofen 250 mg; Drug: Acetaminophen 500 mg

• Study Type: Interventional
• Enrollment (Actual): 290
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male subjects who, at the time of screening, are between 18 and 55 years of age, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests.
2. The subject must have a normal, stable body temperature at Screening and on Day 0. If the subject's oral temperature is not between 97.4°F and 98.8°F, then 2 additional oral temperature readings will be obtained within a 30 minute period. These 3 consecutive temperature readings must be between 97.4°F and 98.8°F, with the highest value within 0.4°F of the lowest temperature value.
3. Body Mass Index (BMI) of 17.5 to 37.0 kg/m2; and a total body weight 50 kg (110 lbs) at Screening.
4. The subject has demonstrably adequate veins, by visual inspection, for IV catheter insertion.

Exclusion Criteria:

1. Evidence or history of clinically significant laboratory abnormality, hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (excluding untreated, asymptomatic, seasonal allergies at the time of dosing) within the last 5 years that may increase the risk associated with study participation.
2. Subjects with any gastrointestinal disorders (eg, gastrectomy, tracheostomy, esophageal surgeries, short gut syndrome, peptic ulcer disease, known or suspected obstructive disease, previous gastrointestinal surgery, felinization of the esophagus, hypomotility of the gastrointestinal track) that could affect the absorption, metabolism, or excretion of the study medication or affect the results of the ingestible thermometer.
3. Subjects at risk for excessive bleeding.
4. Subjects with a history of nasal polyps, angioedema, or significant or actively treated bronchospastic disease.
5. Screening supine blood pressure ≤90 or ≥140 mm Hg (systolic) or ≤50 or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If blood pressure (BP) is ≤90 or ≥140 mm Hg (systolic) or ≤50 or ≥90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three consecutive BP values should be used to determine the subject's eligibility.
6. Screening supine 12 lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at Screening and on Day 1 prior to RSE administration. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three consecutive QTc or QRS values should be used to determine the subject's eligibility.
7. The subject has a history of recurrent or acute or chronic infections of any type or any findings suggestive of occult infection, such as tuberculosis, sinusitis, urinary tract infection, respiratory tract or dental (abscess) infection, etc., or those with a positive QuantiFERON Tuberculosis, Hepatitis B surface antigen, Hepatitis C antibody, and/or Human immunodeficiency virus (HIV) test at Screening. Also excluded are subjects with frequent (more than 3 outbreaks per year), recurrent oral or genital herpes, recurrent herpes zoster, or any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the study.
8. Subjects who have experienced cold/flu symptoms (ie, runny nose, cough, and/or fever) within 2 weeks prior to the first administration of study treatments.
9. Subjects with a reduction in heart rate to ≤50 beats per minute or deemed to be at high risk of syncope and/or hypotension per the clinical judgment of the investigator following a carotid sinus massage procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ibuprofen 250 mg / Acetaminophen 500 mg; Single dose of 2 caplets of Ibuprofen 125 mg / Acetaminophen 250 mg by mouth	Drug: Ibuprofen 250 mg / Acetaminophen 500 mg; Ibuprofen 250 mg / Acetaminophen 500 mg; Other Names: IBU 250 / APAP 500
ACTIVE_COMPARATOR: Ibuprofen 250 mg; Single dose of 2 caplets of IBU 125 mg by mouth	Drug: Ibuprofen 250 mg; Ibuprofen 250 mg; Other Names: IBU 250
ACTIVE_COMPARATOR: Acetaminophen 500 mg; Single dose of 1 APAP 500 mg caplet + 1 placebo caplet by mouth	Drug: Acetaminophen 500 mg; 1 APAP 500 mg caplet; Other Names: APAP 500
PLACEBO_COMPARATOR: Placebo; Single dose of 2 caplets of Placebo by mouth	Drug: Placebo; Placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Weighted Sum of Temperature Difference (WSTD) From 0 to 8 Hours	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).	0 to 8 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Weighted Sum of Temperature Differences (WSTD) From Baseline Through Hours 2, 4 and 6	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).	0 to 2 hours postdose, 0 to 4 hours postdose, 0 to 6 hours postdose
Time to Return to Normal Body Temperature	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.	Baseline (pre-dose) up to 8 hours post dose
Time to Rescue Medication	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.	0 to 8 hours post dose
Time Weighted Sum of Temperature Difference From 6 to 8 Hours	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).	6 to 8 hours postdose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (AEs)	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.	Baseline up to 24 hours after discharge (up to 32 hours)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Smith W, Leyva R, Kellstein D, Arthur E, Cruz-Rivera M. 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. Clin Ther. 2021 Jul;43(7):1213-1227. doi: 10.1016/j.clinthera.2021.05.004. Epub 2021 Jul 23.

Helpful Links

• To obtain contact information for a study center near you, click here.
• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 6, 2016
• Primary Completion (ACTUAL): December 6, 2017
• Study Completion (ACTUAL): December 6, 2017

Study Registration Dates

• First Submitted: May 2, 2016
• First Submitted That Met QC Criteria: May 2, 2016
• First Posted (ESTIMATE): May 4, 2016

Study Record Updates

• Last Update Posted (ACTUAL): December 7, 2018
• Last Update Submitted That Met QC Criteria: November 8, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: ibuprofen; acetaminophen; induced fever; fever
• Additional Relevant MeSH Terms: Body Temperature Changes; Fever; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Acetaminophen; Ibuprofen
• Other Study ID Numbers: B5061002; GEMINI IF (OTHER: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No