Study of the Efficacy and Safety of Intravenous vs Oral Acetaminophen for Treatment of Fever in Healthy Adult Males

NCT00564629 | Completed Phase 3 Results

• 1 other identifier: CPI-APF-303
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the rapidity of onset of antipyretic effect and the efficacy and safety of a single dose of IV acetaminophen (IV APAP) versus oral (PO) acetaminophen in the treatment of fever induced by a standard dose of endotoxin

Conditions

Fever

Outcome Measures

Primary Outcomes (1)

• The Rapidity of Onset of Antipyretic Effect at 2 Hours (Measured as Weighted Sum of Temperature Differences Over 2 Hours, WSTD2)

  This outcome measures when the antipyretic effect begins by statistical analysis of WSTD2, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 2 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.

  0-2 hours

Secondary Outcomes (8)

• Time to a Reduction in Temperature From T0 to T360 Minutes.

  6 hours

• Maximum Temperature Reduction Observed From T0 to T360 Minutes

  T0-T360 minutes

• Subject's Global Evaluation of Study Medication at T360 Minutes

  T360 minutes

• The Percentage of Subjects With Temperature < 38 ºC and < 38.5 ºC at Any Timepoint During the Time From T0 to T360 Minutes

  T0 to T360 minutes

• WSTD3

  0-3 hours

Study Arms (2)

IV acetaminophen plus oral placebo.

EXPERIMENTAL

Administration of a 1 ng/kg body weight test dose of RSE to test for fever response. Observation period of at least 60 minutes to ensure no exaggerated systemic responses, followed by administration of a 4 ng/kg of RSE to induce fever. Randomization to receive 1 g of acetaminophen in 100 ml of intravenous solution and oral placebo.

Drug: Intravenous acetaminophen plus oral placebo; Biological: Reference standard endotoxin (RSE)

Oral acetaminophen plus IV placebo.

ACTIVE COMPARATOR

Administration of a 1 ng/kg body weight test dose of RSE to test for fever response. Observation period of at least 60 minutes to ensure no exaggerated systemic responses, followed by administration of a 4 ng/kg of RSE to induce fever. Randomization to receive oral acetaminophen 1 g plus 100 ml of intravenous placebo solution.

Drug: Oral acetaminophen plus IV placebo; Biological: Reference standard endotoxin (RSE)

Interventions

Intravenous acetaminophen plus oral placebo DRUG

Single dose of 1 gm IV acetaminophen

Also known as: IV APAP

IV acetaminophen plus oral placebo.

Oral acetaminophen plus IV placebo DRUG

Single dose of 1 g PO APAP

Also known as: IV APAP

Oral acetaminophen plus IV placebo.

Reference standard endotoxin (RSE) BIOLOGICAL

To subjects in both study arms: Administration of a 1 ng/kg body weight test dose of RSE to induce fever and test for fever response. Observation period of at least 60 minutes to ensure no exaggerated systemic responses, followed by administration of a 4 ng/kg of RSE to induce fever.

Also known as: RSE

IV acetaminophen plus oral placebo.; Oral acetaminophen plus IV placebo.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written Informed Consent prior to participation in the Study
• Be a healthy male between the ages of 18 and 75 years of age, inclusive, at Randomization
• Have a Body Mass Index (BMI) ≥ 19 and ≤ 45 lbs/in2
• Have the ability to read and understand the Study procedures and have the ability to communicate meaningfully with the Study Investigator and staff
• Be free of physical, mental, or medical conditions which, in the opinion of the Investigator, may confound quantifying assessments for the Study
• Be willing to abstain from smoking cigarettes or using nicotine products from the time of admission to Clinic until Study Completion
• Be free of evidence of infection based upon clinical assessment and blood (Complete Blood Count- CBC) and urine testing
• Have an average baseline oral temperature that is equal to or below 37 ºC (98.6 ºF) and does not vary more than 0.4 ºC (0.7 ºF) from lowest to highest on three assessments performed during a 30-minute period
• Not develop a medically significant allergic or exaggerated systemic response to administration of a test dose of reference standard endotoxin
• Develop a core temperature of at least 38.6 ºC (101.5 ºF) after IV reference standard endotoxin dosed per Study guidelines and have a fever response to endotoxin that is at or near the peak temperature by virtue of two consecutive temperature assessments 5 minutes apart that are within 0.2 ºC (0.4 ºF) of each other

You may not qualify if:

• Has been treated with any medication having antipyretic effects (e.g., corticosteroid,non-steroidal anti-inflammatory drug \[NSAID\], aspirin, or acetaminophen) within 2 days of clinic admission (aspirin at low dose for cardiac prophylaxis is allowed, but should not be taken on the day of the Study)
• Has significant medical disease(s), laboratory abnormalities, or condition(s) that in the Investigator's judgment could compromise the Subject's welfare, ability to communicate with the Study staff, complete Study activities, or would otherwise contraindicate Study participation
• Has known hypersensitivity or contraindication to receiving endotoxin that in the Investigator's clinical judgment merits discontinuation from further Study participation
• Has known hypersensitivity to acetaminophen, the inactive ingredients (excipients) of the intravenous (IV) or oral (PO) acetaminophen formulation or the Rescue Medications (ibuprofen, aspirin, and ketorolac)
• Has known or suspected recent history of alcohol or drug abuse or dependence as defined by Diagnostic Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria
• Has a history of nasal polyps, angioedema, significant or actively treated bronchospastic disease, or any other significant medical condition that contraindicates participation in the Study or receiving endotoxin, Study Medication, or Rescue Medication
• Has an active infection or other disease or condition that may cause abnormal alterations in body temperature
• Has impaired liver function, e.g.Alanine aminotransferase (ALT) greater than or equal to 3 times the upper limit of normal, bilirubin greater than 3.0, active hepatic disease, or evidence of clinically significant liver disease (e.g., cirrhosis or hepatitis)
• Has participated in another clinical Study (investigational or marketed product) within 30 days of Screening

Sponsors & Collaborators

• Mallinckrodt: lead

Study Sites (1)

New Orleans Center for Clinical Research-Knoxville

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

Fever

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Limitations and Caveats

Protocol and statistical analysis plan were amended to clarify endpoints prior to database lock and analysis.

Results Point of Contact

• Title: Lawrence Hill
• Organization: Mallinckrodt Pharmaceuticals

lawrence.hill@mallinckrodt.com

(908) 238-6370

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2007
• First Posted: November 28, 2007
• Study Start: August 1, 2007
• Primary Completion: October 1, 2007
• Study Completion: October 1, 2007
• Last Updated: October 19, 2016
• Results First Posted: September 21, 2010

Record last verified: 2016-10

Locations

US (1)