Trial Outcomes & Findings for Maxigesic IV Phase 3 Bunionectomy Study (NCT NCT02689063)

NCT ID: NCT02689063

Last Updated: 2021-07-06

Results Overview

A Pain Intensity Difference (PID) is the difference between the Visual Analogue Scale (VAS) pain intensity score recorded at baseline and a score recorded at any time after the first dose of study medication. Taken together, a patient's PID scores capture the pain relief profile attributable to the assigned study medication. A high PID score indicates a better pain relief experienced. The extent of pain relief can then be calculated by the Area Under the Curve the PID scores (also referred to as the Sum of Pain Intensity Differences \[SPID\]). SPID48 scores were adjusted by the time interval from baseline to the final VAS score used in the SPID, using the following formula: Time-adjusted SPID48 (mm) = SPID (mm\*hr) / Time (hr) In the event that a patient required rescue medication, the SPID was calculated up until the first Pre-Rescue VAS pain assessment (inclusive).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 276 participants
• Primary outcome timeframe: 48 hours after the first dose
• Results posted on: 2021-07-06

Participant Flow

Participant milestones

Measure	Maxigesic IV intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Overall Study STARTED	75	75	76	50
Overall Study COMPLETED	75	73	73	50
Overall Study NOT COMPLETED	0	2	3	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Maxigesic IV Phase 3 Bunionectomy Study

Baseline characteristics by cohort

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours	Total n=276 Participants Total of all reporting groups
Age, Continuous	42.3 years STANDARD_DEVIATION 11.6 • n=5 Participants	41.9 years STANDARD_DEVIATION 12.5 • n=7 Participants	43.3 years STANDARD_DEVIATION 12.3 • n=5 Participants	41.7 years STANDARD_DEVIATION 12.7 • n=4 Participants	42.4 years STANDARD_DEVIATION 12.2 • n=21 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	58 Participants n=7 Participants	65 Participants n=5 Participants	40 Participants n=4 Participants	225 Participants n=21 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	17 Participants n=7 Participants	11 Participants n=5 Participants	10 Participants n=4 Participants	51 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	18 Participants n=7 Participants	15 Participants n=5 Participants	7 Participants n=4 Participants	58 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	56 Participants n=5 Participants	56 Participants n=7 Participants	60 Participants n=5 Participants	41 Participants n=4 Participants	213 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Region of Enrollment United States	75 Participants n=5 Participants	75 Participants n=7 Participants	76 Participants n=5 Participants	50 Participants n=4 Participants	276 Participants n=21 Participants
Baseline Pain Intensity Level	69.3 scores on a 100mm long scale STANDARD_DEVIATION 15.8 • n=5 Participants	66.2 scores on a 100mm long scale STANDARD_DEVIATION 14.2 • n=7 Participants	68.9 scores on a 100mm long scale STANDARD_DEVIATION 14.4 • n=5 Participants	68.1 scores on a 100mm long scale STANDARD_DEVIATION 15.8 • n=4 Participants	68.1 scores on a 100mm long scale STANDARD_DEVIATION 15.0 • n=21 Participants

PRIMARY outcome

Timeframe: 48 hours after the first dose

Population: All participants randomized (276 in total) received the first dose of study medication under study staff supervision were included in the primary efficacy endpoint analysis.

A Pain Intensity Difference (PID) is the difference between the Visual Analogue Scale (VAS) pain intensity score recorded at baseline and a score recorded at any time after the first dose of study medication. Taken together, a patient's PID scores capture the pain relief profile attributable to the assigned study medication. A high PID score indicates a better pain relief experienced.

The extent of pain relief can then be calculated by the Area Under the Curve the PID scores (also referred to as the Sum of Pain Intensity Differences [SPID]). SPID48 scores were adjusted by the time interval from baseline to the final VAS score used in the SPID, using the following formula:

Time-adjusted SPID48 (mm) = SPID (mm*hr) / Time (hr) In the event that a patient required rescue medication, the SPID was calculated up until the first Pre-Rescue VAS pain assessment (inclusive).

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Summed Pain Intensity Difference (SPID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm).	23.4 score on a scale Interval -34.08 to 74.17	10.4 score on a scale Interval -26.78 to 65.43	9.5 score on a scale Interval -30.68 to 79.98	-1.3 score on a scale Interval -22.42 to 47.5

SECONDARY outcome

Timeframe: 48 hours after the first dose

Population: All participants randomized (276 in total) received the first dose of study medication under study staff supervision (ITT population) were included in the efficacy endpoints analysis.

VAS Pain intensity difference (PID) at each scheduled assessment time point after Time 0.

A Pain Intensity Difference (PID) is the difference between the Visual Analogue Scale (VAS) pain intensity score recorded at baseline and a score recorded at any time after the first dose of study medication. Taken together, a patient's PID scores capture the pain relief profile attributable to the assigned study medication. A high PID score indicates a better pain relief experienced.

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
VAS Pain Intensity Difference (PID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long VAS Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm).	52.50 score on a scale Standard Error 2.73	38.95 score on a scale Standard Error 2.69	45.04 score on a scale Standard Error 3.05	37.24 score on a scale Standard Error 3.90

SECONDARY outcome

Timeframe: 48 hours after the first dose

Population: All the participants who were randomized (276 in total) and received the first dose of double blind treatment (ITT population) were included in the efficacy analysis.

VAS Pain intensity score at each scheduled assessment time point VAS pain intensity score-marking on a 100 mm VAS scale with anchors for "no pain" (0 mm) and "worst pain imaginable" (100 mm). A high VAS score indicates a more intensive pain level experienced.

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
VAS Pain Intensity Score-marking on a 100 mm VAS Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm). A High VAS Score Indicates a More Intensive Pain Level Experienced.	18.43 score on a scale Standard Error 2.85	29.28 score on a scale Standard Error 2.59	27.21 score on a scale Standard Error 3.22	28.22 score on a scale Standard Error 3.48

SECONDARY outcome

Timeframe: 6, 12, 24 hours after the first dose

Population: All participants randomized (276 in total) received the first dose of study medication under study staff supervision (ITT population) were included in the efficacy analysis.

Time adjusted SPID-6, SPID-12, SPID-24 were derived in a similar manner to the Time-adjusted SPID-48 (i.e. up until the first Pre-Rescue VAS inclusive). Please see the primary outcome measure descriptions.

Each of these variables were derived from VAS (Visual Analogue Scale) scores recorded prior to the first dose of rescue medication in the first 6 (to calculate SPID6), 12 (to calculate SPID12) or 24 hours (to calculate SPID24) of the study.

VAS pain intensity scores were obtained by marking on a 100 mm VAS scale with anchors for "no pain" (0 mm) and "worst pain imaginable" (100 mm). The VAS was completed at rest.

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
SPID-6, SPID-12, SPID-24-VAS SPID Over 0 to 6 Hours (SPID-6), Over 0 to 12 Hours (SPID-12), and Over 0 to 24 Hours (SPID-24) After Time 0 (=the First Dose) SPID 6	20.10 score on a scale Interval -34.08 to 61.14	10.13 score on a scale Interval -26.78 to 65.43	9.01 score on a scale Interval -30.68 to 61.92	-1.49 score on a scale Interval -22.42 to 47.5
SPID-6, SPID-12, SPID-24-VAS SPID Over 0 to 6 Hours (SPID-6), Over 0 to 12 Hours (SPID-12), and Over 0 to 24 Hours (SPID-24) After Time 0 (=the First Dose) SPID 12	20.63 score on a scale Interval -34.08 to 71.6	9.42 score on a scale Interval -26.78 to 65.43	8.44 score on a scale Interval -30.68 to 69.4	-1.66 score on a scale Interval -22.42 to 47.5
SPID-6, SPID-12, SPID-24-VAS SPID Over 0 to 6 Hours (SPID-6), Over 0 to 12 Hours (SPID-12), and Over 0 to 24 Hours (SPID-24) After Time 0 (=the First Dose) SPID 24	21.99 score on a scale Interval -34.08 to 77.47	9.59 score on a scale Interval -26.78 to 65.43	8.64 score on a scale Interval -30.68 to 73.19	-1.54 score on a scale Interval -22.42 to 47.5

SECONDARY outcome

Timeframe: 6, 12, 24, 48 hours after the first dose

Population: All participants randomized (276 in total) received the first dose of study medication under study staff supervision (ITT population) were included in the efficacy analysis.

Total Pain Relief (TOTPAR) is a measure of total Area Under the Curve of Pain Relief scores. In the event that a patient required rescue medication, the TOTPAR endpoints were calculated using Pain Relief Assessments recorded prior to the first dose of rescue (i.e. inclusive of the first pre-rescue Pain Relief score).

Pain relief scores were obtained by marking on a 5-point categorical rating at scheduled time points.

The high score means more pain relief experienced:

0 = No pain relief (the pain is the same, or worse, than the starting pain)

1. = A little pain relief (the pain is less than half gone)

2. = some pain relief (the pain is about half gone)

3. = A lot pain relief (the pain is more than half gone)

4. = Complete pain relief (the pain is completely gone) Each of these variables were derived from pain relief scores recorded prior to the first dose of rescue medication in the first 6 (0-48), 12 (0-48), 24 (0-48) or 48 (0-48) hours of the study.

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
TOTPAR-6, TOTPAR-12, TOTPAR-24, TOTPAR-48 TOTPAR 24	22.13 score on a scale*hour Interval 0.0 to 94.6	8.66 score on a scale*hour Interval 0.0 to 66.5	6.51 score on a scale*hour Interval 0.0 to 71.2	2.49 score on a scale*hour Interval 0.0 to 47.1
TOTPAR-6, TOTPAR-12, TOTPAR-24, TOTPAR-48 TOTPAR 6	6.84 score on a scale*hour Interval 0.0 to 22.6	4.59 score on a scale*hour Interval 0.0 to 22.5	3.34 score on a scale*hour Interval 0.0 to 21.2	1.60 score on a scale*hour Interval 0.0 to 11.0
TOTPAR-6, TOTPAR-12, TOTPAR-24, TOTPAR-48 TOTPAR 12	11.86 score on a scale*hour Interval 0.0 to 46.6	6.74 score on a scale*hour Interval 0.0 to 38.9	4.46 score on a scale*hour Interval 0.0 to 35.2	1.82 score on a scale*hour Interval 0.0 to 18.0
TOTPAR-6, TOTPAR-12, TOTPAR-24, TOTPAR-48 TOTPAR 48	43.98 score on a scale*hour Interval 0.0 to 190.5	13.28 score on a scale*hour Interval 0.0 to 138.5	11.95 score on a scale*hour Interval 0.0 to 131.2	4.51 score on a scale*hour Interval 0.0 to 139.2

SECONDARY outcome

Timeframe: 6 hours

Population: All participants randomized (276 in total) received the first dose of study medication under study staff supervision (ITT population) were included in the efficacy analysis.

Two-stopwatch method

1. Start two stopwatches ('Stopwatch A' and 'Stopwatch B') at the same time that the infusion of study drug is initiated. This is Time 0.

2. The participant is given 'Stopwatch A' and instructed to "Stop 'Stopwatch A' when you first feel any pain relief whatsoever. This does not mean you feel completely better, although you might, but when you first feel any relief in the pain you have now." (Perceptible Pain Relief)

3. When the participant stops the 'Stopwatch A', the participant then was asked "Do you consider the pain relief you experienced meaningful?"

4. If the participant answered "No", then the participant was given the "Stopwatch B" and instructed to "Stop 'Stopwatch B' when you feel the pain relief is meaningful to you" (Meaningful Pain Relief)

5. If the subject did not experience "perceptible pain relief, they would retain 'Stopwatch A' for the entire 6 hour evaluation period.

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Time to the Onset of Analgesia-Time to Onset of Analgesia (Measured as Time to Perceptible Pain Relief Confirmed by Meaningful Pain Relief) Using the Two-stopwatch Method	9.4 minutes Interval 6.5 to 11.8	23.9 minutes Interval 13.5 to 39.2	13.8 minutes Interval 6.5 to 24.4	0 minutes Interval 9.9 to 0.0

SECONDARY outcome

Timeframe: 48 hours after the first dose

Population: All participants randomized (276 in total) received the first dose of study medication under study staff supervision (ITT population) were included in the efficacy analysis.

Pain relief score was assessed on a 5-point categorical scale at each scheduled time point after Time 0:

0 = No pain relief (the pain is the same, or worse, than the starting pain)

1. = A little pain relief (the pain is less than half gone)

2. = some pain relief (the pain is about half gone)

3. = A lot pain relief (the pain is more than half gone)

4. = Complete pain relief (the pain is completely gone)

Assessed at scheduled time points:

• 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6 hours after the first dose of the study drug
• Immediately before and 2 hours after each subsequent dose (doses 2-8) of the study drug while awake
• At the end of 48 hours of double-blind treatment period
• Immediately before taking each dose of the rescue medication if additional analgesia is required.
• At the time of withdrawal (if applicable)

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Percentage of Participants With Complete Pain Relief	29 Participants	7 Participants	16 Participants	4 Participants

SECONDARY outcome

Timeframe: 48 hours after the first dose

Population: All participants randomized (276 in total) received the first dose of study medication under study staff supervision (ITT population) were included in the efficacy analysis.

Peak Pain Relief was assessed on Pain Relief scores (on a 5 point categorical rating-please see outcome measure description No. 7) recorded up until the first dose of rescue (First Pre-Rescue Pain Relief score inclusive).

The percentage of participants who achieve the peak pain relief was summarized.

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Percentage of Participants Who Obtained a Peak Pain Relief -Value of 3 ('A Lot of Relief') or 4 ('Complete Relief') Prior to the First Dose of Rescue	22 Participants	11 Participants	4 Participants	3 Participants

SECONDARY outcome

Timeframe: 48 hrs after the first dose

Time to peak pain relief-Peak Pain Relief was assessed on Pain Relief scores recorded up until the first dose of rescue (First Pre-Rescue Pain Relief score inclusive). Time for participants who experienced peak pain relief was summarized.

Note: For the reader to interpret this outcome measure, a very short Time to Peak Pain Relief indicates the absence of analgesic effect for a treatment because peak pain relief was determined prior to the first dose of rescue medication (or 48 hours if no rescue medication was used).

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Time to Peak Pain Relief	4.00 hours Standard Error 1.17	2.46 hours Standard Error 0.86	1.47 hours Standard Error 0.55	0.91 hours Standard Error 0.60

SECONDARY outcome

Timeframe: 48 hrs after the first dose

The percentage of participants who used at lease one dose of rescue medication was summarized in each treatment group

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Percentage of Subjects Using Rescue Medication	56 Participants	70 Participants	70 Participants	48 Participants

SECONDARY outcome

Timeframe: 48 hrs

Time to first use of rescue medication (duration of analgesia)

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Time to the First Dose of Rescue Medication	12.98 hours Standard Error 1.87	5.62 hours Standard Error 0.83	3.09 hours Standard Error 0.35	2.92 hours Standard Error 0.53

SECONDARY outcome

Timeframe: 24, 48 hrs after the first dose

Total use of rescue analgesia over 0 to 24 hours and over 0 to 48 hours

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Total Use of Rescue Medication Total Dose in 48 hrs	22.9 mg Standard Error 2.4	33.1 mg Standard Error 2.7	32.4 mg Standard Error 2.7	44.7 mg Standard Error 3.8
Total Use of Rescue Medication Total Dose in 24 hrs	17.2 mg Standard Error 1.7	23.7 mg Standard Error 1.6	22.1 mg Standard Error 1.4	29.6 mg Standard Error 2.0

SECONDARY outcome

Timeframe: 48 hrs after the first dose

At the end of 48 hours study period, participants will be asked to " How do you rate the study medication?" on a 5 point categorical scale:

1. Poor

2. Fair

3. Good

4. Very Good

5. Excellent The high score means the participants believed that a better treatment for pain relief received.

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
The Percentage of Participants Who Evaluated Their Study Drug as " Excellent" on a 5-point Categorical Scale Global Evaluation of Study Drug	24 Participants	5 Participants	8 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 7

Population: Number of participants who reported at least one AE

Treatment-emergent Adverse events coded to MedDRA v 20.0 Preferred Term and System Organ Class Code were tabulated as the counts and percentages by treatment group.

Outcome measures

Measure	Maxigesic IV n=75 Participants intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 Participants IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 Participants IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 Participants Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Number of Participants With Treatment Emergent Adverse Events (AEs)	52 Participants	45 Participants	58 Participants	39 Participants

Adverse Events

Maxigesic IV

Serious events: 0 serious events

Other events: 52 other events

Deaths: 0 deaths

IV Acetaminophen

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

IV Ibuprofen

Serious events: 0 serious events

Other events: 58 other events

Deaths: 0 deaths

Placebo IV

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Maxigesic IV n=75 participants at risk intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Maxigesic IV: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Acetaminophen n=75 participants at risk IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours IV Acetaminophen: IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	IV Ibuprofen n=76 participants at risk IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours IV Ibuprofen: IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours	Placebo IV n=50 participants at risk Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Placebo IV: Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Gastrointestinal disorders Nausea	29.3% 22/75 • Number of events 37 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	33.3% 25/75 • Number of events 28 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	34.2% 26/76 • Number of events 33 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	32.0% 16/50 • Number of events 22 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Gastrointestinal disorders Vomiting	21.3% 16/75 • Number of events 24 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	14.7% 11/75 • Number of events 12 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	6.6% 5/76 • Number of events 8 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Gastrointestinal disorders Constipation	5.3% 4/75 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	5.3% 4/75 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	5.3% 4/76 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	8.0% 4/50 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Gastrointestinal disorders Dry Mouth	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	3.9% 3/76 • Number of events 3 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/50 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Gastrointestinal disorders Abdominal Discomfort	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Nervous system disorders Dizziness	17.3% 13/75 • Number of events 18 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	9.3% 7/75 • Number of events 8 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	9.2% 7/76 • Number of events 8 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	16.0% 8/50 • Number of events 10 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Nervous system disorders Headache	5.3% 4/75 • Number of events 6 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	6.7% 5/75 • Number of events 5 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	6.6% 5/76 • Number of events 5 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	20.0% 10/50 • Number of events 11 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Nervous system disorders Somnolence	6.7% 5/75 • Number of events 5 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	8.0% 6/75 • Number of events 7 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	7.9% 6/76 • Number of events 7 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	6.0% 3/50 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Nervous system disorders Presyncope	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Nervous system disorders Burning sensation	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Nervous system disorders Dysgeusia	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Nervous system disorders Hypoaesthesia	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Nervous system disorders Sensory disturbance	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
General disorders Infusion site pain	13.3% 10/75 • Number of events 15 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	9.2% 7/76 • Number of events 8 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
General disorders Infusion site extravasation	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	6.6% 5/76 • Number of events 5 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	14.0% 7/50 • Number of events 8 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
General disorders Pyrexia	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.6% 2/76 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
General disorders Feeling hot	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/76 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	4.0% 2/50 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
General disorders Infusion site bruising	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	4.0% 2/50 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
General disorders Oedema peripheral	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/50 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Skin and subcutaneous tissue disorders Pruritus	6.7% 5/75 • Number of events 5 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	4.0% 3/75 • Number of events 3 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	5.3% 4/76 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	4.0% 2/50 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Skin and subcutaneous tissue disorders Hyperhidrosis	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	5.3% 4/75 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	5.3% 4/76 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	6.0% 3/50 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Skin and subcutaneous tissue disorders Erythema	4.0% 3/75 • Number of events 3 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	3.9% 3/76 • Number of events 3 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Skin and subcutaneous tissue disorders Pruritus generalised	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	3.9% 3/76 • Number of events 3 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Skin and subcutaneous tissue disorders Urticaria	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 6 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Musculoskeletal and connective tissue disorders Muscle spasms	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	8.0% 4/50 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Musculoskeletal and connective tissue disorders Muscle twitching	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.6% 2/76 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/50 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.6% 2/76 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/50 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/50 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/50 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Vascular disorders Hot flush	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.6% 2/76 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	6.0% 3/50 • Number of events 3 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Vascular disorders Flushing	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/76 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Vascular disorders Hypotension	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/76 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Metabolism and nutrition disorders Decreased appetite	1.3% 1/75 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	5.3% 4/75 • Number of events 4 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/76 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	4.0% 2/50 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Injury, poisoning and procedural complications Postoperative wound complication	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.7% 2/75 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	3.9% 3/76 • Number of events 3 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	4.0% 2/50 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.6% 2/76 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/50 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/76 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Infections and infestations Post procedural cellulitis	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/76 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	2.0% 1/50 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.
Renal and urinary disorders Polyuria	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	0.00% 0/75 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	1.3% 1/76 • Number of events 1 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.	4.0% 2/50 • Number of events 2 • Participants were followed up for adverse events during the 48 hour study period. Any AEs which were not resolved by the end of the 48 hour study period were followed up at 30 days. The definitions used in the study for the term "adverse event" and "serious adverse event" and the rating of adverse events are described in the Protocol.

Additional Information

Jennifer Zhang -Project Manager

AFT Pharmaceuticals

Phone: + 64 9 488 0232

Email: jenniferz@aftpharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place