Trial Outcomes & Findings for A Comparative Study of JNS013 in Participants With Post-Tooth-Extraction Pain (NCT NCT00737048)

Last Updated: 2016-03-31

Results Overview

Total pain relief was evaluated using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Higher score indicates treatment response.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

328 participants

Primary outcome timeframe

8 hours

Results posted on

2016-03-31

Participant Flow

Participant milestones

Participant milestones
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Overall Study STARTED	132	66	130
Overall Study COMPLETED	129	60	126
Overall Study NOT COMPLETED	3	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Overall Study Physician Decision	0	0	1
Overall Study Adverse Event	0	1	0
Overall Study Worsening of the symptoms	3	5	3

Baseline Characteristics

A Comparative Study of JNS013 in Participants With Post-Tooth-Extraction Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Total n=328 Participants Total of all reporting groups
Age, Continuous	28.1 Years STANDARD_DEVIATION 8.3 • n=5 Participants	27.8 Years STANDARD_DEVIATION 8.6 • n=7 Participants	27.5 Years STANDARD_DEVIATION 8.2 • n=5 Participants	27.8 Years STANDARD_DEVIATION 8.3 • n=4 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	32 Participants n=7 Participants	66 Participants n=5 Participants	159 Participants n=4 Participants
Sex: Female, Male Male	71 Participants n=5 Participants	34 Participants n=7 Participants	64 Participants n=5 Participants	169 Participants n=4 Participants
Visual Analog Scale (VAS) Score	62.28 Units on a scale STANDARD_DEVIATION 9.85 • n=5 Participants	60.33 Units on a scale STANDARD_DEVIATION 7.63 • n=7 Participants	61.32 Units on a scale STANDARD_DEVIATION 8.81 • n=5 Participants	61.51 Units on a scale STANDARD_DEVIATION 9.04 • n=4 Participants

PRIMARY outcome

Timeframe: 8 hours

Population: Final analysis set (FAS) population included all the participants who received the study treatment and had efficacy assessment data.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Total Pain Relief Based on Numerical Rating Scale (NRS) Score	17.7 Units on a scale Standard Deviation 7.91	12.4 Units on a scale Standard Deviation 8.36	13.3 Units on a scale Standard Deviation 8.07

SECONDARY outcome

Timeframe: Baseline up to 8 hours post-administration of study treatment

Population: FAS population included all the participants who received the study treatment and had efficacy assessment data.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Total Pain Relief Based on Numerical Rating Scale (NRS) Score Every 4 Hours up to 8 Hours 0-4 hours	9.6 Units on a scale Standard Deviation 3.90	6.3 Units on a scale Standard Deviation 4.11	7.4 Units on a scale Standard Deviation 3.97
Total Pain Relief Based on Numerical Rating Scale (NRS) Score Every 4 Hours up to 8 Hours 4-8 hours	8.0 Units on a scale Standard Deviation 4.73	6.1 Units on a scale Standard Deviation 4.67	5.9 Units on a scale Standard Deviation 4.71

SECONDARY outcome

Timeframe: Baseline up to 8 hours post-administration of study treatment

Population: FAS population included all the participants who received the study treatment and had efficacy assessment data.

Pain Intensity (PI) was assessed using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Scores were measured at Baseline (that is, 0 hours after tooth extraction) and 8 hours post-administration of study treatments.Pain intensity difference (PID) was calculated (that is, for 0-8 hours, time point \[8 hour\] score minus baseline \[0 hour\] score).

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Sum of Pain Intensity Difference (SPID)	6.4 Units on a scale Standard Deviation 5.90	2.9 Units on a scale Standard Deviation 5.12	4.1 Units on a scale Standard Deviation 5.84

SECONDARY outcome

Timeframe: Baseline up to 8 hours post-administration of study treatment

Population: FAS population included all the participants who received the study treatment and had efficacy assessment data.

The SPRID is the sum of pain relief scores combined with pain intensity difference, score ranging from from (-) 24 (the worst) through 56 (the most improved). Higher score indicates treatment response. Pain Intensity (PI) and Pain relief (PAR) were assessed using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Scores were measured at Baseline (that is, 0 hours after tooth extraction) and at 8 hours post-administration of study treatments. Pain intensity difference (PID) was calculated (that is, for 0-8 hours, time point \[8 hour\] score minus baseline \[0 hour\] score).

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID)	24.0 Units on a scale Standard Deviation 13.03	15.3 Units on a scale Standard Deviation 12.43	17.4 Units on a scale Standard Deviation 13.17

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-administration of study treatment

Population: FAS population included all the participants who received the study treatment and had efficacy assessment data.

Pain was assessed by using Visual Analogue Scale (VAS) score ranges from 0 millimeter (mm)=no pain to 100 mm=worst possible pain. An increase in score from Baseline represented disease progression and decrease represented treatment response.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment Change at Hour 1	-36.79 Units on a scale Standard Deviation 23.603	-12.82 Units on a scale Standard Deviation 27.372	-26.68 Units on a scale Standard Deviation 24.570
Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment Change at Hour 4	-37.70 Units on a scale Standard Deviation 27.266	-21.75 Units on a scale Standard Deviation 29.870	-24.83 Units on a scale Standard Deviation 30.753
Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment Change at Hour 5	-34.78 Units on a scale Standard Deviation 28.173	-17.56 Units on a scale Standard Deviation 29.110	-21.48 Units on a scale Standard Deviation 31.350
Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment Change at Hour 6	-30.20 Units on a scale Standard Deviation 30.932	-15.70 Units on a scale Standard Deviation 31.033	-17.51 Units on a scale Standard Deviation 31.875
Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment Change at Hour 7	-26.37 Units on a scale Standard Deviation 32.456	-13.18 Units on a scale Standard Deviation 30.335	-15.62 Units on a scale Standard Deviation 32.562
Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment Change at Hour 8	-22.85 Units on a scale Standard Deviation 33.116	-13.03 Units on a scale Standard Deviation 30.916	-14.48 Units on a scale Standard Deviation 32.638
Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment Change at Hour 0.5	-22.11 Units on a scale Standard Deviation 23.466	-4.28 Units on a scale Standard Deviation 20.001	-15.50 Units on a scale Standard Deviation 22.336
Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment Change at Hour 2	-42.71 Units on a scale Standard Deviation 23.631	-20.94 Units on a scale Standard Deviation 27.904	-28.43 Units on a scale Standard Deviation 27.583
Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment Change at Hour 3	-41.40 Units on a scale Standard Deviation 26.707	-25.75 Units on a scale Standard Deviation 28.509	-28.40 Units on a scale Standard Deviation 30.544

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-administration of study treatment

Population: FAS population included all the participants who received the study treatment and had efficacy assessment data.

The PID is defined as difference between current pain intensity (PI) and Baseline PI, PI was assessed using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Higher score indicates treatment response. Mean change from Baseline (that is, 0 hours after tooth extraction) at specified end time points were evaluated.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment PID:Change at Hour 0.5	0.6 Units on a scale Standard Deviation 0.67	0.1 Units on a scale Standard Deviation 0.55	0.5 Units on a scale Standard Deviation 0.73
Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment PID:Change at Hour 3	1.1 Units on a scale Standard Deviation 0.87	0.5 Units on a scale Standard Deviation 0.73	0.7 Units on a scale Standard Deviation 0.84
Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment PID:Change at Hour 4	0.9 Units on a scale Standard Deviation 0.85	0.4 Units on a scale Standard Deviation 0.70	0.6 Units on a scale Standard Deviation 0.84
Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment PID:Change at Hour 1	0.9 Units on a scale Standard Deviation 0.71	0.4 Units on a scale Standard Deviation 0.70	0.7 Units on a scale Standard Deviation 0.72
Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment PID:Change at Hour 2	1.1 Units on a scale Standard Deviation 0.78	0.5 Units on a scale Standard Deviation 0.71	0.8 Units on a scale Standard Deviation 0.79
Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment PID:Change at Hour 5	0.8 Units on a scale Standard Deviation 0.85	0.3 Units on a scale Standard Deviation 0.73	0.5 Units on a scale Standard Deviation 0.88
Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment PID:Change at Hour 6	0.7 Units on a scale Standard Deviation 0.88	0.4 Units on a scale Standard Deviation 0.80	0.4 Units on a scale Standard Deviation 0.88
Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment PID:Change at Hour 7	0.6 Units on a scale Standard Deviation 0.92	0.2 Units on a scale Standard Deviation 0.77	0.3 Units on a scale Standard Deviation 0.93
Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment PID:Change at Hour 8	0.5 Units on a scale Standard Deviation 0.94	0.2 Units on a scale Standard Deviation 0.77	0.3 Units on a scale Standard Deviation 0.91

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-administration of study treatment

Population: FAS population included all the participants who received the study treatment and had efficacy assessment data.

Pain Relief (PAR) was assessed using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Higher score indicates treatment response. Mean change from Baseline (that is, 0 hours after tooth extraction) at specified end time points were evaluated.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PAR:Change at Hour 0.5	1.5 Units on a scale Standard Deviation 1.12	0.7 Units on a scale Standard Deviation 0.86	1.3 Units on a scale Standard Deviation 0.99
Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PAR:Change at Hour 1	2.3 Units on a scale Standard Deviation 1.08	1.4 Units on a scale Standard Deviation 1.13	2.0 Units on a scale Standard Deviation 1.11
Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PAR:Change at Hour 2	2.7 Units on a scale Standard Deviation 1.06	1.7 Units on a scale Standard Deviation 1.23	2.0 Units on a scale Standard Deviation 1.18
Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PAR:Change at Hour 3	2.6 Units on a scale Standard Deviation 1.18	1.9 Units on a scale Standard Deviation 1.20	2.0 Units on a scale Standard Deviation 1.21
Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PAR:Change at Hour 4	2.4 Units on a scale Standard Deviation 1.22	1.7 Units on a scale Standard Deviation 1.18	1.8 Units on a scale Standard Deviation 1.20
Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PAR:Change at Hour 5	2.2 Units on a scale Standard Deviation 1.21	1.6 Units on a scale Standard Deviation 1.16	1.6 Units on a scale Standard Deviation 1.27
Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PAR:Change at Hour 6	2.1 Units on a scale Standard Deviation 1.20	1.6 Units on a scale Standard Deviation 1.28	1.5 Units on a scale Standard Deviation 1.25
Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PAR:Change at Hour 7	1.9 Units on a scale Standard Deviation 1.30	1.5 Units on a scale Standard Deviation 1.19	1.4 Units on a scale Standard Deviation 1.27
Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PAR:Change at Hour 8	1.8 Units on a scale Standard Deviation 1.30	1.5 Units on a scale Standard Deviation 1.15	1.4 Units on a scale Standard Deviation 1.25

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-administration of study treatment

Population: FAS population included all the participants who received the study treatment and had efficacy assessment data.

Pain Relief combined with pain Intensity Difference (PRID) represented pain relief scores combined with Pain Intensity difference (PID) scores. PRID score ranges from -3 (the worst) through +7 (the most improved). Higher score indicates treatment response. Mean change from Baseline (that is, 0 hours after tooth extraction) at specified end time points were evaluated.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PRID:Change at Hour 8	2.3 Units on a scale Standard Deviation 2.12	1.7 Units on a scale Standard Deviation 1.78	1.6 Units on a scale Standard Deviation 2.04
Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PRID:Change at Hour 0.5	2.1 Units on a scale Standard Deviation 1.67	0.8 Units on a scale Standard Deviation 1.29	1.8 Units on a scale Standard Deviation 1.61
Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PRID:Change at Hour 1	3.2 Units on a scale Standard Deviation 1.68	1.8 Units on a scale Standard Deviation 1.71	2.7 Units on a scale Standard Deviation 1.69
Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PRID:Change at Hour 2	3.8 Units on a scale Standard Deviation 1.71	2.2 Units on a scale Standard Deviation 1.80	2.8 Units on a scale Standard Deviation 1.85
Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PRID:Change at Hour 3	3.7 Units on a scale Standard Deviation 1.92	2.4 Units on a scale Standard Deviation 1.75	2.7 Units on a scale Standard Deviation 1.92
Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PRID:Change at Hour 4	3.3 Units on a scale Standard Deviation 1.95	2.1 Units on a scale Standard Deviation 1.71	2.4 Units on a scale Standard Deviation 1.92
Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PRID:Change at Hour 5	3.0 Units on a scale Standard Deviation 1.93	1.9 Units on a scale Standard Deviation 1.74	2.1 Units on a scale Standard Deviation 2.03
Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PRID:Change at Hour 6	2.8 Units on a scale Standard Deviation 1.96	1.9 Units on a scale Standard Deviation 1.92	1.8 Units on a scale Standard Deviation 2.00
Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment PRID:Change at Hour 7	2.5 Units on a scale Standard Deviation 2.12	1.7 Units on a scale Standard Deviation 1.81	1.8 Units on a scale Standard Deviation 2.08

SECONDARY outcome

Timeframe: Baseline up to 8 hours post-administration of study treatment

Population: FAS population included all the participants who received the study treatment and had efficacy assessment data. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure \& 'n' signifies those participants who were evaluable for this measure at given time points.

Time to reach the onset of drug efficacy (TOE) means time took by participants for the onset of relief from pain after tooth-extraction and time to recurrence of pain (TOR) after the onset of drug efficacy (that is, duration of drug efficacy) were assessed after study drug treatment.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=102 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=36 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=104 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Time to Reach the Onset of Drug Efficacy and Time to Recurrence of Pain After the Onset of Drug Efficacy TOE (n=102, 36, 104)	47.6 Minutes Standard Deviation 40.88	82.8 Minutes Standard Deviation 82.88	53.5 Minutes Standard Deviation 47.97
Time to Reach the Onset of Drug Efficacy and Time to Recurrence of Pain After the Onset of Drug Efficacy TOR (n=41, 14, 53)	252.5 Minutes Standard Deviation 119.03	207.9 Minutes Standard Deviation 126.44	198.2 Minutes Standard Deviation 120.24

SECONDARY outcome

Timeframe: Baseline up to 8 hours post-administration of study treatment

Population: FAS population included all the participants who received the study treatment and had efficacy assessment data.

Percentage of participants with patient impressions were assessed on categories, that are: worked well; worked; worked a little; and didn't work.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Percentage of Participants With Categorical Score for Patient Impressions Worked well	28.7 Percentage of participants 10	16.4 Percentage of participants 12.43	15.7 Percentage of participants 13.17
Percentage of Participants With Categorical Score for Patient Impressions Worked	55.8 Percentage of participants 6.29	44.3 Percentage of participants 6.04	53.5 Percentage of participants 6.39
Percentage of Participants With Categorical Score for Patient Impressions Worked a little	13.2 Percentage of participants 7.73	24.6 Percentage of participants 7.04	22.8 Percentage of participants 7.69
Percentage of Participants With Categorical Score for Patient Impressions Didn't work	2.3 Percentage of participants	14.8 Percentage of participants	7.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 8 hours post-administration of study treatment

Population: FAS population included all the participants who received the study treatment and had efficacy assessment data.

Participants who were treated with a relief analgesic were assessed. Analgesics are the compounds capable of relieving pain without the loss of consciousness.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Number of Participants Treated With a Relief Analgesic	37 Participants	25 Participants	54 Participants

SECONDARY outcome

Timeframe: Baseline up to 8 hours post-administration of study treatment

Percentage of participants were assessed with treatment response based on "evaluation criteria for efficacy of analgesics in post-tooth-extraction pain" for the efficacy of analgesics used to treat pain following tooth extraction. Participants were assessed as "very effective, effective, somewhat effective and ineffective" for the following categories: Pain suppression (PS), speed of pain relief (SPR), duration of pain relief (DPR), general effectiveness (GE). Participants judged the treatment as "extremely useful, useful, not useful \& could not be assessed" for overall evaluation (OE).

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=107 Participants Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=46 Participants Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=113 Participants Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain GE:very effective (n=107, 46, 113)	2.8 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain GE:effective (n=107, 46, 113)	33.9 Percentage of participants	13.7 Percentage of participants	23.3 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain GE:somewhat effective (n=107, 46, 113)	46.8 Percentage of participants	31.4 Percentage of participants	53.4 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain GE:ineffective (n=107, 46, 113)	16.5 Percentage of participants	54.9 Percentage of participants	23.3 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain OE:Extremely useful (n=107, 46, 113)	0.9 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain OE:not useful (n=107, 46, 113)	87.2 Percentage of participants	96.1 Percentage of participants	82.8 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain OE:could not be assessed (n=107, 46, 113)	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain PS:somewhat effective (n=107, 46, 113)	63.9 Percentage of participants	42.9 Percentage of participants	67.5 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain PS:very effective (n=107, 46, 113)	19.4 Percentage of participants	8.2 Percentage of participants	9.6 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain PS:effective (n=107, 46, 113)	2.8 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain PS:ineffective (n=107, 46, 113)	13.9 Percentage of participants	49.0 Percentage of participants	22.8 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain SPR:very effective (n=107, 46, 113)	56.9 Percentage of participants	21.6 Percentage of participants	44.8 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain SPR:effective (n=107, 46, 113)	26.6 Percentage of participants	21.6 Percentage of participants	28.4 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain SPR:somewhat effective (n=107, 46, 113)	7.3 Percentage of participants	15.7 Percentage of participants	10.3 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain SPR:ineffective (n=107, 46, 113)	9.2 Percentage of participants	41.2 Percentage of participants	16.4 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain DPR:very effective (n=41, 14, 53)	39.0 Percentage of participants	28.6 Percentage of participants	24.5 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain DPR:effective (n=41, 14, 53)	26.8 Percentage of participants	35.7 Percentage of participants	28.3 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain DPR:somewhat effective (n=41, 14, 53)	17.1 Percentage of participants	7.1 Percentage of participants	20.8 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain DPR:ineffective (n=41, 14, 53)	17.1 Percentage of participants	28.6 Percentage of participants	26.4 Percentage of participants
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain OE:useful (n=107, 46, 113)	11.9 Percentage of participants	3.9 Percentage of participants	17.2 Percentage of participants

Adverse Events

Tramadol Hydrochloride Plus Acetaminophen and Placebo

Serious events: 0 serious events

Other events: 82 other events

Deaths: 0 deaths

Tramadol Hydrochloride and Placebo

Serious events: 0 serious events

Other events: 40 other events

Deaths: 0 deaths

Acetaminophen and Placebo

Serious events: 1 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tramadol Hydrochloride Plus Acetaminophen and Placebo n=132 participants at risk Tramadol hydrochloride and acetaminophen combination tablet was administered as 75 and 650 milligram respectively, as single oral dose of two tablets, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (\>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Tramadol Hydrochloride and Placebo n=66 participants at risk Tramadol hydrochloride was administered as 75 milligram, as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Acetaminophen and Placebo n=130 participants at risk Acetaminophen was administered as 650 milligram as single oral dose of two capsules, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed \>= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).
Immune system disorders Drug hypersensitivity	0.00% 0/132 • Baseline up to Day 8 An adverse event is any untoward medical occurrence in a clinical study participant administered with study treatment. It can be any unfavorable and unintended sign/abnormal finding, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	0.00% 0/66 • Baseline up to Day 8 An adverse event is any untoward medical occurrence in a clinical study participant administered with study treatment. It can be any unfavorable and unintended sign/abnormal finding, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	0.77% 1/130 • Baseline up to Day 8 An adverse event is any untoward medical occurrence in a clinical study participant administered with study treatment. It can be any unfavorable and unintended sign/abnormal finding, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Other adverse events

Additional Information

Medical Director

JANSSEN PHARMACEUTICAL. K.K. , Neuroscience Department, Clinical Science Division

Phone: +81-3-4411-5509

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the Principal Investigator is that the Sponsor can review results communications prior to public release.
Publication restrictions are in place

Restriction type: OTHER