Trial Outcomes & Findings for SB-705498 Dental Pain Study After Tooth Extraction (NCT NCT00281684)

Last Updated: 2019-01-28

Results Overview

Pain intensity was assessed using VAS. These assessments were then summarized to give a weighted mean score. The VAS was a subjective assessment of post-operative pain intensity. The participants rated the pain intensity at the time of assessment by marking a line on a 100 millimeter (mm) (0 to 100 mm) long scale. A line placed on the extreme left (0 mm) indicated no pain and extreme right (100 mm) indicated worst pain imaginable. This scale has no subscales. Only those participants available at the specified time points were analyzed.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

145 participants

Primary outcome timeframe

Up to 10 hours post-dose

Results posted on

2019-01-28

Participant Flow

This study was conducted at 3 centers in the United Kingdom, 1 center in Korea, Republic of and 1 center in Italy from 07 December 2005 to 03 October 2007. A total of 145 participants were enrolled into the study.

Participants already scheduled for 3rd molar tooth extraction, who were otherwise healthy, were recruited for this study. As soon as reasonably possible after completion of tooth extraction (but within 1 hour), participants were randomized to treatment and dosed with the study medication whilst local anesthetic was still active.

Participant milestones

Participant milestones
Measure	Placebo Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg Eligible participants received a single dose of SB705498 400 milligram (mg) capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol European Pharmacopoeia \[Ph Eur\] 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Overall Study STARTED	37	36	34	38
Overall Study COMPLETED	36	36	33	38
Overall Study NOT COMPLETED	1	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg Eligible participants received a single dose of SB705498 400 milligram (mg) capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol European Pharmacopoeia \[Ph Eur\] 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Overall Study Lost to Follow-up	0	0	1	0
Overall Study Withdrawal by Subject	1	0	0	0

Baseline Characteristics

SB-705498 Dental Pain Study After Tooth Extraction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=36 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=34 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.	Total n=145 Participants Total of all reporting groups
Age, Continuous	27.5 Years STANDARD_DEVIATION 7.37 • n=5 Participants	27.0 Years STANDARD_DEVIATION 6.45 • n=7 Participants	26.0 Years STANDARD_DEVIATION 7.26 • n=5 Participants	27.0 Years STANDARD_DEVIATION 6.36 • n=4 Participants	26.9 Years STANDARD_DEVIATION 6.82 • n=21 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	18 Participants n=7 Participants	20 Participants n=5 Participants	19 Participants n=4 Participants	76 Participants n=21 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	18 Participants n=7 Participants	14 Participants n=5 Participants	19 Participants n=4 Participants	69 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants	12 Participants n=4 Participants	43 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	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
Race (NIH/OMB) White	25 Participants n=5 Participants	29 Participants n=7 Participants	18 Participants n=5 Participants	23 Participants n=4 Participants	95 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 10 hours post-dose

Population: The Intent-to-Treat (ITT) population which comprised of all participants randomized to treatment, who took the study medication and who had at least one post-dose assessment. The ITT population did not include participants who took rescue medication or withdrew within the first 120 minutes after administration of study medication.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=34 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=32 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=36 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Mean of Pain Intensity Based on the Visual Analogue Scale (VAS)	37.45 Scores on a Scale Standard Deviation 22.474	34.95 Scores on a Scale Standard Deviation 26.076	38.84 Scores on a Scale Standard Deviation 22.869	17.15 Scores on a Scale Standard Deviation 26.094

SECONDARY outcome

Timeframe: Up to 10 hours post Baseline (Day 1)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Pain intensity was assessed using VRS. Participants also used a 4-point categorical VRS for the subjective assessment of postoperative pain. The score and it corresponding intensity was such that 0= no pain, 1= mild, 2= moderate and 3= severe. The VRS was collected as an independent measure of the participant's pain and was not prospectively correlated to the study participant's numerical score (number of millimeters) on the VAS. Participants were provided with a worksheet with a list of adjectives to read and they were asked to select the word by checking the box that best described their level of pain. The number associated with the adjective chosen by the participant constituted the pain intensity. Baseline (Day 1) value was the value obtained immediately prior to administration of study drug. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=34 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=33 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline 1 hour post-randomization	0.3 Scores on a Scale Standard Deviation 0.51	0.3 Scores on a Scale Standard Deviation 0.80	0.6 Scores on a Scale Standard Deviation 0.62	0.3 Scores on a Scale Standard Deviation 0.51
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline 2 hour post-randomization	1.3 Scores on a Scale Standard Deviation 0.89	1.1 Scores on a Scale Standard Deviation 1.05	1.3 Scores on a Scale Standard Deviation 0.90	0.9 Scores on a Scale Standard Deviation 0.87
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline 3 hour post-randomization	1.3 Scores on a Scale Standard Deviation 0.75	1.0 Scores on a Scale Standard Deviation 0.91	1.4 Scores on a Scale Standard Deviation 0.79	1.0 Scores on a Scale Standard Deviation 1.07
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline 6 hour post-randomization	1.1 Scores on a Scale Standard Deviation 0.76	1.0 Scores on a Scale Standard Deviation 0.89	0.9 Scores on a Scale Standard Deviation 0.60	1.0 Scores on a Scale Standard Deviation 1.06
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline Pre-dose	0.0 Scores on a Scale Standard Deviation 0.00	0.0 Scores on a Scale Standard Deviation 0.00	0.0 Scores on a Scale Standard Deviation 0.00	0.0 Scores on a Scale Standard Deviation 0.00
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline 4 hour post-randomization	1.3 Scores on a Scale Standard Deviation 0.77	1.1 Scores on a Scale Standard Deviation 1.03	1.2 Scores on a Scale Standard Deviation 0.90	1.0 Scores on a Scale Standard Deviation 1.06
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline 5 hour post-randomization	1.2 Scores on a Scale Standard Deviation 0.83	0.9 Scores on a Scale Standard Deviation 0.83	0.8 Scores on a Scale Standard Deviation 0.60	1.1 Scores on a Scale Standard Deviation 0.99
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline 7 hour post-randomization	1.2 Scores on a Scale Standard Deviation 0.83	1.1 Scores on a Scale Standard Deviation 0.83	0.9 Scores on a Scale Standard Deviation 0.64	0.8 Scores on a Scale Standard Deviation 1.08
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline 8 hour post-randomization	1.0 Scores on a Scale Standard Deviation 0.74	0.9 Scores on a Scale Standard Deviation 0.88	0.8 Scores on a Scale Standard Deviation 0.71	0.8 Scores on a Scale Standard Deviation 1.28
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline 9 hour post-randomization	1.0 Scores on a Scale Standard Deviation 0.77	0.6 Scores on a Scale Standard Deviation 0.74	0.8 Scores on a Scale Standard Deviation 0.71	0.7 Scores on a Scale Standard Deviation 1.23
Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline 10 hour post-randomization	1.1 Scores on a Scale Standard Deviation 0.83	0.8 Scores on a Scale Standard Deviation 1.04	0.6 Scores on a Scale Standard Deviation 0.53	0.5 Scores on a Scale Standard Deviation 1.18

SECONDARY outcome

Timeframe: Baseline (Day 1) to 10 hours post Baseline

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Pain intensity was assessed using VAS. The VAS was a subjective assessment of post-operative pain intensity. The participants rated the pain intensity at the time of the assessment by marking a line on a 100 millimeter (mm) (0 to 100 mm) long scale. A line placed on the extreme left (0 mm) indicated no pain and extreme right (100 mm) indicated worst pain imaginable. This scale has no subscales. The Baseline (Day 1) value was the value obtained immediately prior to administration of study drug. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=34 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=33 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline 2 hour post randomization	27.8 Scores on a Scale Standard Deviation 22.02	26.9 Scores on a Scale Standard Deviation 30.74	34.6 Scores on a Scale Standard Deviation 24.72	15.2 Scores on a Scale Standard Deviation 25.76
Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline 1 hour post randomization	4.7 Scores on a Scale Standard Deviation 9.12	8.0 Scores on a Scale Standard Deviation 17.66	10.0 Scores on a Scale Standard Deviation 16.55	4.6 Scores on a Scale Standard Deviation 9.40
Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline 3 hour post randomization	27.1 Scores on a Scale Standard Deviation 17.10	13.7 Scores on a Scale Standard Deviation 18.96	39.0 Scores on a Scale Standard Deviation 25.52	15.7 Scores on a Scale Standard Deviation 26.09
Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline 4 hour post randomization	29.6 Scores on a Scale Standard Deviation 20.16	18.6 Scores on a Scale Standard Deviation 23.22	36.4 Scores on a Scale Standard Deviation 26.07	16.8 Scores on a Scale Standard Deviation 25.08
Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline 5 hour post randomization	25.8 Scores on a Scale Standard Deviation 18.98	11.5 Scores on a Scale Standard Deviation 23.56	25.8 Scores on a Scale Standard Deviation 20.96	14.3 Scores on a Scale Standard Deviation 21.50
Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline 6 hour post randomization	25.9 Scores on a Scale Standard Deviation 19.00	13.8 Scores on a Scale Standard Deviation 24.91	28.3 Scores on a Scale Standard Deviation 21.19	10.5 Scores on a Scale Standard Deviation 26.51
Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline 7 hour post randomization	25.9 Scores on a Scale Standard Deviation 21.55	15.7 Scores on a Scale Standard Deviation 24.64	25.6 Scores on a Scale Standard Deviation 19.65	8.0 Scores on a Scale Standard Deviation 28.17
Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline 8 hour post randomization	19.5 Scores on a Scale Standard Deviation 18.59	12.2 Scores on a Scale Standard Deviation 25.28	24.0 Scores on a Scale Standard Deviation 18.88	6.5 Scores on a Scale Standard Deviation 28.92
Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline 9 hour post randomization	17.0 Scores on a Scale Standard Deviation 16.94	6.6 Scores on a Scale Standard Deviation 19.81	19.6 Scores on a Scale Standard Deviation 15.03	10.3 Scores on a Scale Standard Deviation 32.63
Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline 10 hour post randomization	17.1 Scores on a Scale Standard Deviation 20.52	7.3 Scores on a Scale Standard Deviation 20.27	17.0 Scores on a Scale Standard Deviation 15.47	7.2 Scores on a Scale Standard Deviation 25.19

SECONDARY outcome

Timeframe: Within 24 hours of administration of study drug

Population: ITT Population.

Duration of Analgesic Effect (Time to First Rescue medication from study drug administration) is presented. Ibuprofen 400 mg was provided as rescue medication to be taken as required. The time when the rescue medication was administered was recorded on the case report form.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=34 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=33 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Elapsed Time From Study Drug Administration to Rescue Analgesic Request	5.13 Hours Interval 2.08 to 10.33	4.27 Hours Interval 2.02 to 19.7	3.12 Hours Interval 2.12 to 11.08	6.88 Hours Interval 2.28 to 11.92

SECONDARY outcome

Timeframe: Prior to first rescue medication use and at 10 and 24 hours post randomization

Population: ITT population.

Participants subjectively assessed their overall impression (global evaluation) of the study medication using a 4-point categorical scale, where 1= poor, 2= fair, 3= good and 4= excellent. Participants were provided with a list of adjectives and were asked to select the word by checking the box that best rated the study medication that they received for pain relief. The number associated with the adjective chosen by the participant constituted the global evaluation score. The study coordinator or designee transcribed the number corresponding to the selected adjective onto the case report form. The Global Evaluation was completed prior to receiving the first rescue medication, at 10 hours post-dose and prior to discharge from the unit.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=34 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=33 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization At 10 hour post-randomization: Fair	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization Pre-rescue: Poor	9 Participants	7 Participants	10 Participants	8 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization Pre-rescue: Fair	9 Participants	10 Participants	6 Participants	9 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization Pre-rescue: Good	8 Participants	6 Participants	6 Participants	12 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization Pre-rescue: Excellent	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization At 10 hour post-randomization: Poor	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization At 10 hour post-randomization: Good	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization At 10 hour post-randomization: Excellent	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization At 24 hour post-randomization: Poor	11 Participants	9 Participants	14 Participants	9 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization At 24 hour post-randomization: Fair	10 Participants	9 Participants	6 Participants	11 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization At 24 hour post-randomization: Good	9 Participants	12 Participants	9 Participants	13 Participants
Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization At 24 hour post-randomization: Excellent	3 Participants	4 Participants	3 Participants	3 Participants

SECONDARY outcome

Timeframe: From the time of rescue medication to 10 hours post randomization

Population: ITT Population. Only those participants who used rescue medication were analyzed.

Pain intensity was assessed using VAS. VAS was a subjective assessment of post-operative pain intensity. Participants rated the pain intensity at the time of assessment by marking a line on a 100 mm (0 to 100 mm) long scale. A line placed on extreme left, i.e., 0 mm indicated no pain and extreme right that is 100 mm indicated worst pain imaginable. This scale has no subscales.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=34 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=33 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
VAS Mean Pain Scores From the Time of Rescue Medication up to 10 Hours Post Randomization 8 hour post-randomization	64.9 Scores on a Scale Standard Deviation 20.83	61.5 Scores on a Scale Standard Deviation 21.43	60.4 Scores on a Scale Standard Deviation 25.67	55.8 Scores on a Scale Standard Deviation 24.56
VAS Mean Pain Scores From the Time of Rescue Medication up to 10 Hours Post Randomization 10 hour post-randomization	65.7 Scores on a Scale Standard Deviation 20.70	59.9 Scores on a Scale Standard Deviation 21.31	59.9 Scores on a Scale Standard Deviation 25.29	53.7 Scores on a Scale Standard Deviation 24.29
VAS Mean Pain Scores From the Time of Rescue Medication up to 10 Hours Post Randomization 3 hour post-randomization	74.7 Scores on a Scale Standard Deviation 18.68	70.1 Scores on a Scale Standard Deviation 17.87	61.7 Scores on a Scale Standard Deviation 26.50	70.9 Scores on a Scale Standard Deviation 22.57
VAS Mean Pain Scores From the Time of Rescue Medication up to 10 Hours Post Randomization 4 hour post-randomization	69.4 Scores on a Scale Standard Deviation 19.14	64.9 Scores on a Scale Standard Deviation 22.12	59.2 Scores on a Scale Standard Deviation 26.64	65.5 Scores on a Scale Standard Deviation 26.05
VAS Mean Pain Scores From the Time of Rescue Medication up to 10 Hours Post Randomization 5 hour post-randomization	66.4 Scores on a Scale Standard Deviation 20.25	61.9 Scores on a Scale Standard Deviation 21.83	59.8 Scores on a Scale Standard Deviation 26.53	63.5 Scores on a Scale Standard Deviation 27.58
VAS Mean Pain Scores From the Time of Rescue Medication up to 10 Hours Post Randomization 6 hour post-randomization	63.9 Scores on a Scale Standard Deviation 20.79	61.9 Scores on a Scale Standard Deviation 21.83	59.3 Scores on a Scale Standard Deviation 25.65	56.2 Scores on a Scale Standard Deviation 27.23
VAS Mean Pain Scores From the Time of Rescue Medication up to 10 Hours Post Randomization 7 hour post-randomization	64.9 Scores on a Scale Standard Deviation 20.83	61.9 Scores on a Scale Standard Deviation 21.83	60.4 Scores on a Scale Standard Deviation 25.67	55.1 Scores on a Scale Standard Deviation 26.03
VAS Mean Pain Scores From the Time of Rescue Medication up to 10 Hours Post Randomization 9 hour post-randomization	65.7 Scores on a Scale Standard Deviation 20.70	59.9 Scores on a Scale Standard Deviation 21.31	60.6 Scores on a Scale Standard Deviation 26.20	55.0 Scores on a Scale Standard Deviation 24.40

SECONDARY outcome

Timeframe: Up to 10 hour post-dose

Population: ITT Population.

Ibuprofen 400 mg was provided as rescue medication to be taken as required. The time that rescue medication was administered was recorded on the case report form. Number of participants requiring rescue medication up to 10 hour post-dose are presented.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=34 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=33 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Number of Participants Requiring Rescue Medication Over Time 3 hour post-dose	12 Participants	16 Participants	16 Participants	7 Participants
Number of Participants Requiring Rescue Medication Over Time 1 hour post-dose	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Requiring Rescue Medication Over Time 2 hour post-dose	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Requiring Rescue Medication Over Time 4 hour post-dose	17 Participants	19 Participants	20 Participants	11 Participants
Number of Participants Requiring Rescue Medication Over Time 5 hour post-dose	19 Participants	23 Participants	22 Participants	14 Participants
Number of Participants Requiring Rescue Medication Over Time 6 hour post-dose	21 Participants	23 Participants	24 Participants	19 Participants
Number of Participants Requiring Rescue Medication Over Time 7 hour post-dose	22 Participants	23 Participants	25 Participants	21 Participants
Number of Participants Requiring Rescue Medication Over Time 8 hour post-dose	22 Participants	24 Participants	25 Participants	24 Participants
Number of Participants Requiring Rescue Medication Over Time 9 hour post-dose	23 Participants	26 Participants	24 Participants	25 Participants
Number of Participants Requiring Rescue Medication Over Time 10 hour post-dose	23 Participants	26 Participants	26 Participants	27 Participants

SECONDARY outcome

Timeframe: From first dose of rescue medication to second dose of rescue medication

Population: ITT Population.

Ibuprofen 400 mg was provided as rescue medication to be taken as required. The time that rescue medication was administered was recorded on the case report form. Number of participants using the second rescue medication from the time the first rescue medication was used are presented.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=34 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=33 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Number of Participants From First Rescue Medication Use to Second Rescue Analgesic Request	6 Participants	5 Participants	10 Participants	9 Participants

SECONDARY outcome

Timeframe: Up to Follow-up (28 days)

Population: The Safety population which comprised of all participants who were randomized and took at least one capsule of study medication.

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=36 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=34 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Number of Participants With Adverse Events (AE) Over Time	16 Participants	10 Participants	14 Participants	14 Participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population.

ECGs were recorded with the participant lying supine, having rested in this position for at least 5 minutes before each recording. Full 12 lead ECGs were recorded using an ECG device that automatically calculated the heart rate and measured PR, QRS, RR, QT and QT, QT corrected by Bazett's formula (QTcB) and QT corrected by Fridericia's formula (QTcF) intervals. Paper ECG traces were recorded at a standard paper speed of 25 millimeter/second and gain of 1mVolt/10 millimeter, using 2.5x4 format with lead II rhythm strip. Cardiac intervals were checked by a physician and then transcribed into the case report form. Number of participants with abnormal (not clinically significant \[NCS\] and clinically significant \[CS\]) ECG findings are presented.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=36 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=34 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 4 hour post-dose, Abnormal-NCS	8 Participants	9 Participants	15 Participants	7 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Pre-dose, Abnormal-NCS	9 Participants	7 Participants	14 Participants	10 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Pre-dose, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 2 hour post-dose, Abnormal-NCS	16 Participants	10 Participants	15 Participants	7 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 2 hour post-dose, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 4 hour post-dose, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 6 hour post-dose, Abnormal-NCS	4 Participants	9 Participants	8 Participants	9 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 6 hour post-dose, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 8 hour post-dose, Abnormal-NCS	7 Participants	9 Participants	11 Participants	6 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 8 hour post-dose, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 10 hour post-dose, Abnormal-NCS	8 Participants	11 Participants	13 Participants	8 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 10 hour post-dose, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 24 hour post-dose, Abnormal-NCS	7 Participants	12 Participants	10 Participants	8 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 24 hour post-dose, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 24 hours post-dose

Population: Safety population.

Continuous ambulatory Holter ECG monitoring was performed for a 24-hour period at screening (Day -14 to Day -1) and from pre-dose (post surgery) to approximately 20 hours post-randomization. Number of participants with second degree atrioventricular block over 24 hours by Holter tape are presented.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=36 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=34 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Number of Participants With Second Degree Atrioventricular Block Over 24 Hours by Holter Tape	0 Participants	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to 24 hours post Baseline

Population: Safety population. Only those participants available at the specified time points were analyzed.

Supine SBP and DBP measurements were performed with the participant in a supine position after the participant has rested for at least 5 minutes. Assessment was completed pre-dose and then at 2, 4, 6, 8, 10 and discharge (approximately 24 hour) post randomization. Baseline (Day 1) value was the value obtained immediately prior to administration of study drug. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=36 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=34 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: 8 hour post-randomization	1.44 Millimeters of mercury (mmHg) Standard Deviation 6.631	1.25 Millimeters of mercury (mmHg) Standard Deviation 8.005	-1.50 Millimeters of mercury (mmHg) Standard Deviation 7.712	-0.08 Millimeters of mercury (mmHg) Standard Deviation 7.691
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: 10 hour post-randomization	0.67 Millimeters of mercury (mmHg) Standard Deviation 6.612	-0.25 Millimeters of mercury (mmHg) Standard Deviation 6.971	-0.91 Millimeters of mercury (mmHg) Standard Deviation 6.824	-0.87 Millimeters of mercury (mmHg) Standard Deviation 8.217
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: 10 hour post-randomization	2.31 Millimeters of mercury (mmHg) Standard Deviation 11.887	-0.44 Millimeters of mercury (mmHg) Standard Deviation 8.433	1.06 Millimeters of mercury (mmHg) Standard Deviation 9.335	2.18 Millimeters of mercury (mmHg) Standard Deviation 8.693
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: 2 hour post-randomization	7.62 Millimeters of mercury (mmHg) Standard Deviation 8.388	5.94 Millimeters of mercury (mmHg) Standard Deviation 9.411	5.62 Millimeters of mercury (mmHg) Standard Deviation 7.758	2.84 Millimeters of mercury (mmHg) Standard Deviation 8.952
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: 4 hour post-randomization	3.11 Millimeters of mercury (mmHg) Standard Deviation 7.770	2.36 Millimeters of mercury (mmHg) Standard Deviation 7.772	4.06 Millimeters of mercury (mmHg) Standard Deviation 8.489	2.16 Millimeters of mercury (mmHg) Standard Deviation 8.106
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: 6 hour post-randomization	4.03 Millimeters of mercury (mmHg) Standard Deviation 7.129	-0.33 Millimeters of mercury (mmHg) Standard Deviation 8.384	-2.18 Millimeters of mercury (mmHg) Standard Deviation 6.930	2.50 Millimeters of mercury (mmHg) Standard Deviation 7.783
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: 24 hour post-randomization	-0.61 Millimeters of mercury (mmHg) Standard Deviation 6.677	-1.97 Millimeters of mercury (mmHg) Standard Deviation 7.113	-1.74 Millimeters of mercury (mmHg) Standard Deviation 6.426	-2.32 Millimeters of mercury (mmHg) Standard Deviation 7.956
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: 2 hour post-randomization	8.08 Millimeters of mercury (mmHg) Standard Deviation 10.087	5.25 Millimeters of mercury (mmHg) Standard Deviation 9.488	7.18 Millimeters of mercury (mmHg) Standard Deviation 10.641	2.39 Millimeters of mercury (mmHg) Standard Deviation 10.640
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: 4 hour post-randomization	5.08 Millimeters of mercury (mmHg) Standard Deviation 10.133	3.97 Millimeters of mercury (mmHg) Standard Deviation 9.782	7.09 Millimeters of mercury (mmHg) Standard Deviation 11.145	4.42 Millimeters of mercury (mmHg) Standard Deviation 11.377
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: 6 hour post-randomization	5.06 Millimeters of mercury (mmHg) Standard Deviation 10.656	0.11 Millimeters of mercury (mmHg) Standard Deviation 10.717	1.21 Millimeters of mercury (mmHg) Standard Deviation 9.380	2.84 Millimeters of mercury (mmHg) Standard Deviation 9.474
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: 8 hour post-randomization	2.08 Millimeters of mercury (mmHg) Standard Deviation 9.533	1.28 Millimeters of mercury (mmHg) Standard Deviation 10.859	-0.65 Millimeters of mercury (mmHg) Standard Deviation 7.908	0.08 Millimeters of mercury (mmHg) Standard Deviation 8.556
Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: 24 hour post-randomization	0.58 Millimeters of mercury (mmHg) Standard Deviation 8.897	-1.03 Millimeters of mercury (mmHg) Standard Deviation 9.238	-0.32 Millimeters of mercury (mmHg) Standard Deviation 8.138	-0.13 Millimeters of mercury (mmHg) Standard Deviation 8.777

SECONDARY outcome

Timeframe: Baseline (Day 1) to 24 hours post Baseline

Population: Safety population. Only those participants available at the specified time points were analyzed.

Tympanic temperature was assessed at screening, pre-dose and then at 2, 4, 6, 8, 10 and discharge (approximately 24 hours) post-Baseline. Temperature was also recorded at the follow-up visit. The Baseline (Day 1) value was the value obtained immediately prior to administration of study drug. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=36 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=34 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Change From Baseline for Vital Signs-Body Temperature 2 hour post randomization	0.17 Degree Celsius Standard Deviation 0.345	0.28 Degree Celsius Standard Deviation 0.635	0.47 Degree Celsius Standard Deviation 0.399	0.07 Degree Celsius Standard Deviation 0.446
Change From Baseline for Vital Signs-Body Temperature 6 hour post randomization	0.47 Degree Celsius Standard Deviation 0.423	0.59 Degree Celsius Standard Deviation 0.708	0.75 Degree Celsius Standard Deviation 0.481	0.41 Degree Celsius Standard Deviation 0.487
Change From Baseline for Vital Signs-Body Temperature 4 hour post randomization	0.27 Degree Celsius Standard Deviation 0.402	0.49 Degree Celsius Standard Deviation 0.604	0.74 Degree Celsius Standard Deviation 0.446	0.24 Degree Celsius Standard Deviation 0.404
Change From Baseline for Vital Signs-Body Temperature 8 hour post randomization	0.50 Degree Celsius Standard Deviation 0.525	0.33 Degree Celsius Standard Deviation 0.699	0.67 Degree Celsius Standard Deviation 0.546	0.45 Degree Celsius Standard Deviation 0.654
Change From Baseline for Vital Signs-Body Temperature 10 hour post randomization	0.43 Degree Celsius Standard Deviation 0.569	0.28 Degree Celsius Standard Deviation 0.598	0.46 Degree Celsius Standard Deviation 0.532	0.32 Degree Celsius Standard Deviation 0.625
Change From Baseline for Vital Signs-Body Temperature 24 hour post randomization	0.26 Degree Celsius Standard Deviation 0.421	0.37 Degree Celsius Standard Deviation 0.809	0.45 Degree Celsius Standard Deviation 0.618	0.34 Degree Celsius Standard Deviation 0.624

SECONDARY outcome

Timeframe: Up to 28 days

Population: Safety population.

Hematology parameters included hemoglobin, packed cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, red blood cell count, white blood cell (WBC) count, platelets and differential WBC count. Clinical chemistry parameters included sodium, potassium, urea, creatinine, total protein, albumin, total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GGT), lactate dehydrogenase, calcium, magnesium, phosphate, cholesterol, high density lipoprotein cholesterol, triglycerides, glucose and creatinine kinase. Only those parameters for which at least one value of potential clinical concern was reported are presented.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=36 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=34 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Calcium, Low at Follow-up	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Alkaline Phosphatase, High at Follow-up	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Alanine Amino Transferase, High at screening	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Alanine Amino Transferase, High at Follow-up	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Total Bilirubin, High at screening	2 Participants	1 Participants	0 Participants	6 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Total Bilirubin, High at 24 hour post-dose	5 Participants	3 Participants	6 Participants	8 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Total Bilirubin, High at Follow-up	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Creatine Kinase, High at screening	2 Participants	1 Participants	2 Participants	5 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Creatine Kinase, High at 24 hour post-dose	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Creatine Kinase, High at Follow-up	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern GGT, High at screening	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern GGT, High at 24 hour post-dose	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern GGT, High at Follow-up	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Glucose, High at 24 hour post-dose	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Glucose, High at Follow-up	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Glucose, Low at Follow-up	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Hemoglobin, Low at Follow-up	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Potassium, High at screening	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Potassium, High at 24 hour post-dose	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern Sodium, Low at Follow-up	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern WBC count, High at 24 hour post-dose	0 Participants	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Population: Safety population.

Urinalysis parameters included protein, glucose, ketones, bilirubin, blood, urobilinogen, urine leukocyte esterase (ULE) test for detecting WBC (via dipstick method). The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine can be read as negative, Trace, +, ++, +++ and ++++ indicating proportional concentrations in the urine sample. The results above ++ that is ++, +++ and ++++ were reported as abnormal and the corresponding parameters were considered as abnormal parameters. Number of participants with abnormal urinalysis parameters were reported.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=36 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=34 Participants Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 Participants Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Number of Participants With Abnormal Urine Parameters Urine Bilirubin, ++	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urine Parameters Urine Ketones, ++	2 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Urine Parameters Urine Leukocyte Esterase, ++	2 Participants	7 Participants	3 Participants	3 Participants
Number of Participants With Abnormal Urine Parameters Urine microscop-Cellular Casts, ++	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urine Parameters Urine microscop-Culture, ++	2 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urine Parameters Urine Occult Blood, ++	1 Participants	2 Participants	2 Participants	2 Participants
Number of Participants With Abnormal Urine Parameters Urine Ketones, +++	0 Participants	3 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Urine Parameters Urine Leukocyte Esterase, +++	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urine Parameters Urine microscopy-Culture, +++	1 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urine Parameters Urine Occult Blood, +++	4 Participants	3 Participants	3 Participants	2 Participants

SECONDARY outcome

Timeframe: At pre-dose on Baseline (Day 1) and at between 20-40 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 10 hours post dose and at final follow-up (Day 28)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Cannulation of the forearm vein was performed prior to surgery for serial pharmacokinetic blood sampling. The cannula was kept patent by means of a 0.9% saline lock. Blood was sampled via the intravenous cannula with 1 mL of blood being withdrawn prior to each sample and discarded. Venipuncture was allowed if necessary (e.g., cannulation failure).

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=33 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Area Under Curve (AUC)(0-rescue) and AUC(0-t) of SB705498 AUC(0-rescue)	1.6684 Microgramhour per milliliter (ugh/mL) Geometric Coefficient of Variation 82.462	2.2589 Microgramhour per milliliter (ugh/mL) Geometric Coefficient of Variation 82.989	—	—
Area Under Curve (AUC)(0-rescue) and AUC(0-t) of SB705498 AUC(0-t)	3.1467 Microgramhour per milliliter (ugh/mL) Geometric Coefficient of Variation 51.813	4.8338 Microgramhour per milliliter (ugh/mL) Geometric Coefficient of Variation 38.963	—	—

SECONDARY outcome

Timeframe: At pre-dose on Baseline (Day 1) and at between 20-40 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 10 hours post dose and at final follow-up (Day 28)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=33 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Plasma Concentrations: Average Concentration (C-avg) [0-rescue] and Maximum Concentration (C-max) of SB705498 C-avg (0-rescue)	0.3387 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 42.682	0.5472 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 36.126	—	—
Plasma Concentrations: Average Concentration (C-avg) [0-rescue] and Maximum Concentration (C-max) of SB705498 C-max	0.5855 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 43.101	0.8903 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 41.759	—	—

SECONDARY outcome

Timeframe: At pre-dose (Baseline) and at between 20-40minutes and at 1, 1.5, 2, 3, 4, 6, 8, 10 hours post randomization and at final follow-up (Day 28)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=33 Participants Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Time Prior to the First Measurable Concentration (T-lag) and Time to Maximum Observed Plasma Concentration (T-max) T-lag	0.00 Hour Interval 0.0 to 0.5	0.00 Hour Interval 0.0 to 0.0	—	—
Time Prior to the First Measurable Concentration (T-lag) and Time to Maximum Observed Plasma Concentration (T-max) T-max	1.500 Hour Interval 1.0 to 8.15	1.500 Hour Interval 1.0 to 10.15	—	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

SB705498 400 mg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

SB705498 1000 mg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Co-Codamol

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=37 participants at risk Eligible participants received a single dose of SB705498 matching placebo capsules (4 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 400 mg n=36 participants at risk Eligible participants received a single dose of SB705498 400 mg capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days.	SB705498 1000 mg n=34 participants at risk Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days.	Co-Codamol n=38 participants at risk Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days.
Nervous system disorders Headache	13.5% 5/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	14.7% 5/34 • Up to 28 days Safety population was used for this analysis.	10.5% 4/38 • Up to 28 days Safety population was used for this analysis.
Nervous system disorders Dizziness	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	7.9% 3/38 • Up to 28 days Safety population was used for this analysis.
Nervous system disorders Dizziness postural	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	2.9% 1/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Nervous system disorders Syncope vasovagal	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	2.6% 1/38 • Up to 28 days Safety population was used for this analysis.
Gastrointestinal disorders Nausea	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	7.9% 3/38 • Up to 28 days Safety population was used for this analysis.
Gastrointestinal disorders Diarrhoea	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	2.6% 1/38 • Up to 28 days Safety population was used for this analysis.
Gastrointestinal disorders Vomiting	5.4% 2/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Gastrointestinal disorders Constipation	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	2.6% 1/38 • Up to 28 days Safety population was used for this analysis.
Gastrointestinal disorders Dyspepsia	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Gastrointestinal disorders Gingival pain	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Gastrointestinal disorders Mouth ulceration	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Gastrointestinal disorders Toothache	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
General disorders Feeling hot	5.4% 2/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	5.9% 2/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
General disorders Pyrexia	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	5.9% 2/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
General disorders Catheter site pain	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
General disorders Chest discomfort	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	2.9% 1/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
General disorders Feeling abnormal	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	2.6% 1/38 • Up to 28 days Safety population was used for this analysis.
General disorders Feeling cold	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	2.9% 1/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
General disorders Feeling of body temperature change	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	2.9% 1/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
General disorders Influenza like illness	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	2.9% 1/34 • Up to 28 days Safety population was used for this analysis.	2.6% 1/38 • Up to 28 days Safety population was used for this analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	2.9% 1/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Ear and labyrinth disorders Ear pain	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	2.6% 1/38 • Up to 28 days Safety population was used for this analysis.
Skin and subcutaneous tissue disorders Rash	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	2.9% 1/34 • Up to 28 days Safety population was used for this analysis.	2.6% 1/38 • Up to 28 days Safety population was used for this analysis.
Cardiac disorders Atrioventricular block second degree	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	2.9% 1/34 • Up to 28 days Safety population was used for this analysis.	2.6% 1/38 • Up to 28 days Safety population was used for this analysis.
Eye disorders Asthenopia	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Eye disorders Conjunctivitis	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Investigations ACTH stimulation test	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	2.6% 1/38 • Up to 28 days Safety population was used for this analysis.
Investigations Blood bilirubin increased	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	2.6% 1/38 • Up to 28 days Safety population was used for this analysis.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Musculoskeletal and connective tissue disorders Pain in jaw	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Immune system disorders Seasonal allergy	2.7% 1/37 • Up to 28 days Safety population was used for this analysis.	0.00% 0/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Infections and infestations Nasopharyngitis	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.
Vascular disorders Haematoma	0.00% 0/37 • Up to 28 days Safety population was used for this analysis.	2.8% 1/36 • Up to 28 days Safety population was used for this analysis.	0.00% 0/34 • Up to 28 days Safety population was used for this analysis.	0.00% 0/38 • Up to 28 days Safety population was used for this analysis.