Trial Outcomes & Findings for Study of the Efficacy and Safety of Intravenous vs Oral Acetaminophen for Treatment of Fever in Healthy Adult Males (NCT NCT00564629)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

105 participants

Primary outcome timeframe

0-2 hours

Results posted on

2016-10-19

Participant Flow

Healthy Adult males at one site in the United States

Eligible subjects were given intravenous (IV) endotoxin 1 ng/kg as a test dose and observed for 1 hour. Next, subjects were administered a 4 ng/kg pyrogenic IV endotoxin dose and monitored until a core temperature of at least 38.6 ºC was reached. Subjects achieving a sufficient fever response were then randomly assigned to study treatments.

Participant milestones

Participant milestones
Measure	Oral Acetaminophen (PO APAP) 1 g group of subjects randomly selected to receive 1 g of oral acetaminophen as the study treatment	Intravenous Acetaminophen (IV APAP) 1 g / 100 ml Solution group of subjects randomly selected to receive 1 g /100 ml of intravenous acetaminophen solution as the study treatment
Overall Study STARTED	51	54
Overall Study COMPLETED	36	45
Overall Study NOT COMPLETED	15	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Oral Acetaminophen (PO APAP) 1 g group of subjects randomly selected to receive 1 g of oral acetaminophen as the study treatment	Intravenous Acetaminophen (IV APAP) 1 g / 100 ml Solution group of subjects randomly selected to receive 1 g /100 ml of intravenous acetaminophen solution as the study treatment
Overall Study Vomited within 2 hours of receiving drug	15	9

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PO APAP 1 g n=51 Participants group of subjects randomly selected to receive 1 g of oral acetaminophen and 100 ml of intravenous placebo solution as the study treatment	IV APAP 1 g / 100 ml Solution n=54 Participants group of subjects randomly selected to receive 1 g of acetaminophen in 100 ml of intravenous solution and oral placebo as the study treatment	Total n=105 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	51 Participants n=5 Participants	54 Participants n=7 Participants	105 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	32.1 years STANDARD_DEVIATION 9.07 • n=5 Participants	33.8 years STANDARD_DEVIATION 11.6 • n=7 Participants	33 years STANDARD_DEVIATION 10.52 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	54 Participants n=7 Participants	105 Participants n=5 Participants
Region of Enrollment United States	51 participants n=5 Participants	54 participants n=7 Participants	105 participants n=5 Participants

PRIMARY outcome

Timeframe: 0-2 hours

Population: mITT population defined as all randomized subjects who received at least 1 full dose of oral study medication (subject not vomiting within 2 hours after oral study drug) or 1 full dose of IV study medication(subject having received all 100 mls solution). This analysis was performed with imputation for non-physiological temperature swing zone effect

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.

Outcome measures

Outcome measures
Measure	IV APAP 1 g / 100 ml Solution n=45 Participants mITT-Intravenous Acetaminophen 1g	PO APAP 1 g n=36 Participants mITT-Oral Acetaminophen 1 g
The Rapidity of Onset of Antipyretic Effect at 2 Hours (Measured as Weighted Sum of Temperature Differences Over 2 Hours, WSTD2)	0.3 Degrees Celsius Standard Deviation 0.41	0.6 Degrees Celsius Standard Deviation 0.55

SECONDARY outcome

Timeframe: 6 hours

Population: Analysis was performed on the mITT population.

This outcome measures how much time it took to observe a decrease in subjects' core body temperature by 0.8 ºC, 1.0 ºC, and 1.5 ºC from the temperature at T0 and from the temperature at the peak after T0 through T360 (6 hours). The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.

Outcome measures

Outcome measures
Measure	IV APAP 1 g / 100 ml Solution n=45 Participants mITT-Intravenous Acetaminophen 1g	PO APAP 1 g n=36 Participants mITT-Oral Acetaminophen 1 g
Time to a Reduction in Temperature From T0 to T360 Minutes. reduction in temp of 0.8 ºC from the peak T0-T360	3.5 Hours Standard Deviation 1.23	2.4 Hours Standard Deviation 1.16
Time to a Reduction in Temperature From T0 to T360 Minutes. reduction in temp of 1.0 ºC from the peak T0-T360	3.8 Hours Standard Deviation 0.87	2.9 Hours Standard Deviation 1.16
Time to a Reduction in Temperature From T0 to T360 Minutes. reduction in temperature of 1.5 ºC from T0 temp	5.7 Hours Standard Deviation 0.45	5.6 Hours Standard Deviation 0.64
Time to a Reduction in Temperature From T0 to T360 Minutes. reduction in temperature of 0.8 ºC from T0 temp	4.8 Hours Standard Deviation 0.96	4.7 Hours Standard Deviation 1.41
Time to a Reduction in Temperature From T0 to T360 Minutes. reduction in temperature of 1.0 ºC from T0 temp	5.1 Hours Standard Deviation 0.85	5.0 Hours Standard Deviation 1.24
Time to a Reduction in Temperature From T0 to T360 Minutes. reduction in temp of 1.5 ºC from the peak T0-T360	5.1 Hours Standard Deviation 0.17	4.2 Hours Standard Deviation 1.19

SECONDARY outcome

Timeframe: T0-T360 minutes

Population: Analysis performed on the mITT population.

This outcome measures the maximum core temperature reduction observed from T0 to T360 minutes. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.

Outcome measures

Outcome measures
Measure	IV APAP 1 g / 100 ml Solution n=45 Participants mITT-Intravenous Acetaminophen 1g	PO APAP 1 g n=36 Participants mITT-Oral Acetaminophen 1 g
Maximum Temperature Reduction Observed From T0 to T360 Minutes	-0.8 Degrees Celsius Standard Deviation 0.46	-1.1 Degrees Celsius Standard Deviation 0.42

SECONDARY outcome

Timeframe: T360 minutes

Population: Analysis performed on the mITT population.

This outcome measures how satisfied the subject was with the study treatment. The subject was asked to answer "Overall, how would you rate study treatments?" at T360 minutes using a 4-point categorical scale (0=poor, 1=fair, 2=good, 3=excellent).

Outcome measures

Outcome measures
Measure	IV APAP 1 g / 100 ml Solution n=45 Participants mITT-Intravenous Acetaminophen 1g	PO APAP 1 g n=36 Participants mITT-Oral Acetaminophen 1 g
Subject's Global Evaluation of Study Medication at T360 Minutes Poor (0)	0 participants	2 participants
Subject's Global Evaluation of Study Medication at T360 Minutes Fair (1)	7 participants	2 participants
Subject's Global Evaluation of Study Medication at T360 Minutes Good (2)	18 participants	11 participants
Subject's Global Evaluation of Study Medication at T360 Minutes Excellent (3)	20 participants	21 participants

SECONDARY outcome

Timeframe: T0 to T360 minutes

Population: Analysis performed on mITT population.

This outcome measures what percentage of total subjects had a temperature \< 38 ºC and \< 38.5 ºC at any timepoint during the time from T0 to T360 minutes.

Outcome measures

Outcome measures
Measure	IV APAP 1 g / 100 ml Solution n=45 Participants mITT-Intravenous Acetaminophen 1g	PO APAP 1 g n=36 Participants mITT-Oral Acetaminophen 1 g
The Percentage of Subjects With Temperature < 38 ºC and < 38.5 ºC at Any Timepoint During the Time From T0 to T360 Minutes temperature < 38 ºC	40 percentage of participants	67 percentage of participants
The Percentage of Subjects With Temperature < 38 ºC and < 38.5 ºC at Any Timepoint During the Time From T0 to T360 Minutes temperature < 38.5 ºC	84 percentage of participants	92 percentage of participants

SECONDARY outcome

Timeframe: 0-3 hours

This outcome measure is a statistical analysis of WSTD3, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 3 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.

Outcome measures

Outcome measures
Measure	IV APAP 1 g / 100 ml Solution n=45 Participants mITT-Intravenous Acetaminophen 1g	PO APAP 1 g n=36 Participants mITT-Oral Acetaminophen 1 g
WSTD3	0.2 degrees Celsius Standard Deviation 0.73	0.5 degrees Celsius Standard Deviation 0.85

SECONDARY outcome

Timeframe: 0-4 hours

This outcome measure is a statistical analysis of WSTD4, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 4 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.

Outcome measures

Outcome measures
Measure	IV APAP 1 g / 100 ml Solution n=45 Participants mITT-Intravenous Acetaminophen 1g	PO APAP 1 g n=36 Participants mITT-Oral Acetaminophen 1 g
WSTD4	-0.20 degrees Celsius Standard Deviation 1.06	-0.02 degrees Celsius Standard Deviation 1.12

SECONDARY outcome

Timeframe: 0-5 hours

This outcome measure is a statistical analysis of WSTD5, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 5 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.

Outcome measures

Outcome measures
Measure	IV APAP 1 g / 100 ml Solution n=45 Participants mITT-Intravenous Acetaminophen 1g	PO APAP 1 g n=36 Participants mITT-Oral Acetaminophen 1 g
WSTD5	-0.7 degrees Celsius Standard Deviation 1.43	-0.7 degrees Celsius Standard Deviation 1.41

SECONDARY outcome

Timeframe: 0-6 hours

This outcome measure is a statistical analysis of WSTD6, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 6 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.

Outcome measures

Outcome measures
Measure	IV APAP 1 g / 100 ml Solution n=45 Participants mITT-Intravenous Acetaminophen 1g	PO APAP 1 g n=36 Participants mITT-Oral Acetaminophen 1 g
WSTD6	-1.4 degrees Celsius Standard Deviation 1.88	-1.7 degrees Celsius Standard Deviation 1.70

Adverse Events

Oral Acetaminophen (PO APAP) 1 g

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Intravenous Acetaminophen (IV APAP) 1 g / 100 ml Solution

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Oral Acetaminophen (PO APAP) 1 g n=51 participants at risk group of subjects randomly selected to receive 1 g of oral acetaminophen as the study treatment	Intravenous Acetaminophen (IV APAP) 1 g / 100 ml Solution n=54 participants at risk group of subjects randomly selected to receive 1 g /100 ml of intravenous acetaminophen solution as the study treatment
Gastrointestinal disorders Diarrhoea	9.8% 5/51 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject. TEAEs are adverse events that start on or after the start of study medication.	7.4% 4/54 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject. TEAEs are adverse events that start on or after the start of study medication.
Gastrointestinal disorders Vomiting	25.5% 13/51 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject. TEAEs are adverse events that start on or after the start of study medication.	11.1% 6/54 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject. TEAEs are adverse events that start on or after the start of study medication.
Nervous system disorders Headache	7.8% 4/51 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject. TEAEs are adverse events that start on or after the start of study medication.	9.3% 5/54 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject. TEAEs are adverse events that start on or after the start of study medication.

Additional Information

Lawrence Hill

Mallinckrodt Pharmaceuticals

Phone: (908) 238-6370

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Neither the Institution nor the Investigator shall have the right to publish the Institution findings without prior written consent of Cadence.
Publication restrictions are in place

Restriction type: OTHER