Trial Outcomes & Findings for An Efficacy and Safety Study of Acetaminophen Plus Tramadol Hydrochloride (JNS013) in Participants With Chronic Pain (NCT NCT00736853)

Last Updated: 2013-09-26

Results Overview

The pain relief was regarded as insufficient, if either of the following was met, a) the value of average pain intensity felt in daily living during the past 24 hours (Visual analog scale 24 \[VAS24\] ) on 2 consecutive days in double-blind period worsened greater than 15 millimeter (mm) compared with the average VAS24 during 3 days before the end of open-label period, b) when the participant asked for discontinuation of treatment with the study drug because of insufficient pain relief.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

321 participants

Primary outcome timeframe

Day 28 of double-blind period

Results posted on

2013-09-26

Participant Flow

Participant milestones

Participant milestones
Measure	Tramadol Hydrochloride and Acetaminophen (Open-Label) Fixed dose combination of tramadol 37.5 milligram (mg)/acetaminophen 325 mg, 1 or 2 tablets 4 times daily was given for one week; dose level was fixed for each participant during the second week based on analgesic efficacy and tolerability (maximum daily dose was 8 tablets).	Tramadol Hydrochloride and Acetaminophen (Double-Blind) Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Open-Label Period STARTED	319	0	0
Open-Label Period Treated	277	0	0
Open-Label Period COMPLETED	187	0	0
Open-Label Period NOT COMPLETED	132	0	0
Double-Blind Period STARTED	0	94	93
Double-Blind Period COMPLETED	0	70	45
Double-Blind Period NOT COMPLETED	0	24	48

Reasons for withdrawal

Reasons for withdrawal
Measure	Tramadol Hydrochloride and Acetaminophen (Open-Label) Fixed dose combination of tramadol 37.5 milligram (mg)/acetaminophen 325 mg, 1 or 2 tablets 4 times daily was given for one week; dose level was fixed for each participant during the second week based on analgesic efficacy and tolerability (maximum daily dose was 8 tablets).	Tramadol Hydrochloride and Acetaminophen (Double-Blind) Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Open-Label Period Physician Decision	2	0	0
Open-Label Period Adverse Event	31	0	0
Open-Label Period Withdrawal by Subject	16	0	0
Open-Label Period Started but not treated	42	0	0
Open-Label Period Failed to meet the transfer criteria	40	0	0
Open-Label Period Unable to attend hospital appointments	1	0	0
Double-Blind Period Lack of Efficacy	0	19	42
Double-Blind Period Adverse Event	0	3	2
Double-Blind Period Withdrawal by Subject	0	1	4
Double-Blind Period Ineligible to participate the study	0	1	0

Baseline Characteristics

An Efficacy and Safety Study of Acetaminophen Plus Tramadol Hydrochloride (JNS013) in Participants With Chronic Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=277 Participants Fixed dose combination of tramadol 37.5 milligram (mg)/acetaminophen 325 mg, 1 or 2 tablets 4 times daily was given for one week; dose level was fixed for each participant during the second week based on analgesic efficacy and tolerability (maximum daily dose was 8 tablets) during the open-label period. Participants received placebo or fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg (same dose which was used in second week of open-label period) in double-blind period.
Age Continuous	57.0 years STANDARD_DEVIATION 17.5 • n=5 Participants
Sex: Female, Male Female	168 Participants n=5 Participants
Sex: Female, Male Male	109 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 28 of double-blind period

Population: Efficacy analysis set included participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 Participants Matching placebo was given up to 4 weeks.
Number of Participants With Insufficient Pain Relief After the Start of Double-Blind Period	20 number of participants	43 number of participants

SECONDARY outcome

Timeframe: Day 1 of open-label period and Day 1 of double-blind period

Population: Efficacy analysis set included participants who received at least one dose of study drug.

Pain over the last 24 hours was assessed by using VAS score ranges from 0 mm=no pain to 100 mm=worst possible pain. An increase in score from Baseline represented disease progression and decrease represented improvement.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=277 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Change in the Visual Analog Scale for the Last 24 Hours (VAS24) Value at the Start of the Double-Blind Period From the Baseline Value at the Start of the Open-Label Period Day 1 of open-label period	66.27 mm Standard Deviation 13.69	—
Change in the Visual Analog Scale for the Last 24 Hours (VAS24) Value at the Start of the Double-Blind Period From the Baseline Value at the Start of the Open-Label Period Change at Day 1 of double-blind period	-28.17 mm Standard Deviation 21.16	—

SECONDARY outcome

Timeframe: Day 1 and Day 28 of double-blind period

Population: Efficacy analysis set included participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 Participants Matching placebo was given up to 4 weeks.
Change in the VAS24 Value From the Baseline at the Final Time Point of the Double-Blind Period Day 1	30.33 mm Standard Deviation 17.47	31.18 mm Standard Deviation 16.59
Change in the VAS24 Value From the Baseline at the Final Time Point of the Double-Blind Period Change at Day 28	-0.67 mm Standard Deviation 18.14	6.21 mm Standard Deviation 22.50

SECONDARY outcome

Timeframe: Pre-dose and post-dose at 2 hours, 4 hours on Day 1, and Day 8 of open-label period

Population: Efficacy analysis set included participants who received at least one dose of study drug. Here 'n' signifies number of participants evaluable for this outcome measure at each time point.

PI was evaluated on a 4-stage scale with a score ranging from 0 to 3, wherein 0=no pain and 3=severe pain.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=277 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Mean Pain Intensity (PI) Score During Open-Label Period Day 1; Pre-dose (n=275)	1.7 units on a scale Standard Deviation 0.56	—
Mean Pain Intensity (PI) Score During Open-Label Period Day 1; 2 hours after dosing (n=274)	1.2 units on a scale Standard Deviation 0.62	—
Mean Pain Intensity (PI) Score During Open-Label Period Day 1; 4 hours after dosing (n=274)	1.1 units on a scale Standard Deviation 0.65	—
Mean Pain Intensity (PI) Score During Open-Label Period Day 8; Pre-dose (n=219)	1.2 units on a scale Standard Deviation 0.43	—
Mean Pain Intensity (PI) Score During Open-Label Period Day 8; 2 hours after dosing (n=219)	1.0 units on a scale Standard Deviation 0.49	—
Mean Pain Intensity (PI) Score During Open-Label Period Day 8; 4 hours after dosing (n=219)	0.9 units on a scale Standard Deviation 0.55	—

SECONDARY outcome

Timeframe: Pre-dose and post-dose at 2 hours, 4 hours on Day 1, 8, 15, 22 and 28 of double-blind period

Population: Efficacy analysis set included participants who received at least one dose of the study drug. Here 'n' signifies number of participants evaluable at each time point for each arm respectively.

The PI was evaluated on a 4-stage scale with a score ranging from 0 to 3, wherein 0=no pain and 3=severe pain.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 Participants Matching placebo was given up to 4 weeks.
Mean PI Score During Double-Blind Period Day 28; 2 hours after dosing (n=72, 47)	1.0 units on a scale Standard Deviation 0.44	1.0 units on a scale Standard Deviation 0.51
Mean PI Score During Double-Blind Period Day 1; Pre-dose (n=84, 89)	1.2 units on a scale Standard Deviation 0.37	1.2 units on a scale Standard Deviation 0.37
Mean PI Score During Double-Blind Period Day 1; 2 hours after dosing (n=84, 89)	1.0 units on a scale Standard Deviation 0.44	1.1 units on a scale Standard Deviation 0.43
Mean PI Score During Double-Blind Period Day 1; 4 hours after dosing (n=84, 89)	1.0 units on a scale Standard Deviation 0.49	1.1 units on a scale Standard Deviation 0.47
Mean PI Score During Double-Blind Period Day 8; Pre-dose (n=74, 48)	1.2 units on a scale Standard Deviation 0.39	1.2 units on a scale Standard Deviation 0.42
Mean PI Score During Double-Blind Period Day 8; 2 hours after dosing (n=74, 48)	1.0 units on a scale Standard Deviation 0.47	1.1 units on a scale Standard Deviation 0.58
Mean PI Score During Double-Blind Period Day 8; 4 hours after dosing (n=74, 48)	0.9 units on a scale Standard Deviation 0.51	1.1 units on a scale Standard Deviation 0.43
Mean PI Score During Double-Blind Period Day 15; Pre-dose (n=67, 41)	1.1 units on a scale Standard Deviation 0.33	1.1 units on a scale Standard Deviation 0.33
Mean PI Score During Double-Blind Period Day 15; 2 hours after dosing (n=67, 41)	1.0 units on a scale Standard Deviation 0.46	1.0 units on a scale Standard Deviation 0.50
Mean PI Score During Double-Blind Period Day 15; 4 hours after dosing (n=67, 41)	0.8 units on a scale Standard Deviation 0.51	0.9 units on a scale Standard Deviation 0.52
Mean PI Score During Double-Blind Period Day 22; Pre-dose (n=63, 40)	1.1 units on a scale Standard Deviation 0.30	1.2 units on a scale Standard Deviation 0.38
Mean PI Score During Double-Blind Period Day 22, 2 hours after dosing (n=63, 40)	1.0 units on a scale Standard Deviation 0.42	1.0 units on a scale Standard Deviation 0.50
Mean PI Score During Double-Blind Period Day 22; 4 hours after dosing (n=63, 40)	0.9 units on a scale Standard Deviation 0.49	1.0 units on a scale Standard Deviation 0.50
Mean PI Score During Double-Blind Period Day 28; Pre-dose (n=72, 47)	1.1 units on a scale Standard Deviation 0.33	1.2 units on a scale Standard Deviation 0.41
Mean PI Score During Double-Blind Period Day 28; 4 hours after dosing (n=72, 47)	0.9 units on a scale Standard Deviation 0.50	1.0 units on a scale Standard Deviation 0.49

SECONDARY outcome

Timeframe: Pre-dose, and post-dose at 2 hours, 4 hours on Day 1, and Day 8 of open-label period

Population: Efficacy analysis set included participants who received at least one dose of study drug. Here 'n' signifies number of participants evaluable for this outcome measure at each time point.

The PID was calculated as PI at pre-dose on Day 1, 8 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=277 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Mean Pain Intensity Difference (PID) During the Open-Label Period Day 1; 2 hours after dosing (n=274)	0.4 units on a scale Standard Deviation 0.59	—
Mean Pain Intensity Difference (PID) During the Open-Label Period Day 1; 4 hours after dosing (n=274)	0.5 units on a scale Standard Deviation 0.66	—
Mean Pain Intensity Difference (PID) During the Open-Label Period Day 8; 2 hours after dosing (n=219)	0.2 units on a scale Standard Deviation 0.50	—
Mean Pain Intensity Difference (PID) During the Open-Label Period Day 8; 4 hours after dosing (n=219)	0.3 units on a scale Standard Deviation 0.52	—

SECONDARY outcome

Timeframe: Pre-dose, and post-dose at 2 hours, 4 hours on Day 1, 8, 15, 22 and 28 of double-blind period

Population: Efficacy analysis set included participants received at least one dose of the study drug. Here 'n' signifies number of participants evaluable at each time point for each arm respectively.

The PID was calculated as PI at pre-dose on Day 1, 8, 15, 22, 28 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8, 15, 22, 28 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 Participants Matching placebo was given up to 4 weeks.
Mean PID During the Double-Blind Period Day 1; 2 hours after dosing (n=84, 89)	0.2 units on a scale Standard Deviation 0.40	0.1 units on a scale Standard Deviation 0.34
Mean PID During the Double-Blind Period Day 1; 4 hours after dosing (n=84, 89)	0.2 units on a scale Standard Deviation 0.49	0.1 units on a scale Standard Deviation 0.42
Mean PID During the Double-Blind Period Day 8; 2 hours after dosing (n=74, 48)	0.2 units on a scale Standard Deviation 0.39	0.1 units on a scale Standard Deviation 0.46
Mean PID During the Double-Blind Period Day 8; 4 hours after dosing (n=74, 48)	0.3 units on a scale Standard Deviation 0.50	0.2 units on a scale Standard Deviation 0.38
Mean PID During the Double-Blind Period Day 15; 2 hours after dosing (n=67, 41)	0.1 units on a scale Standard Deviation 0.36	0.2 units on a scale Standard Deviation 0.44
Mean PID During the Double-Blind Period Day 15; 4 hours after dosing (n=67, 41)	0.3 units on a scale Standard Deviation 0.49	0.2 units on a scale Standard Deviation 0.51
Mean PID During the Double-Blind Period Day 22; 2 hours after dosing (n=63, 40)	0.1 units on a scale Standard Deviation 0.35	0.2 units on a scale Standard Deviation 0.42
Mean PID During the Double-Blind Period Day 22; 4 hours after dosing (n=63, 40)	0.2 units on a scale Standard Deviation 0.42	0.2 units on a scale Standard Deviation 0.42
Mean PID During the Double-Blind Period Day 28; 2 hours after dosing (n=72, 47)	0.2 units on a scale Standard Deviation 0.36	0.2 units on a scale Standard Deviation 0.41
Mean PID During the Double-Blind Period Day 28; 4 hours after dosing (n=72, 47)	0.3 units on a scale Standard Deviation 0.44	0.2 units on a scale Standard Deviation 0.43

SECONDARY outcome

Timeframe: 2 hours, 4 hours post-dose on Day 1, and Day 8 of open-label period

Population: Efficacy analysis set included participants who received at least one dose of study drug. Here 'n' signifies number of participants evaluable for this outcome measure at each time point.

PAR was evaluated based on 5-stage scale with a score ranging from 0 to 4, wherein, 0=no relief and 4=complete relief.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=277 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Mean Pain Relief (PAR) Score During the Open-Label Period Day 1; 2 hours after dosing (n=274)	1.2 units on a scale Standard Deviation 0.97	—
Mean Pain Relief (PAR) Score During the Open-Label Period Day 1; 4 hours after dosing (n=274)	1.4 units on a scale Standard Deviation 1.01	—
Mean Pain Relief (PAR) Score During the Open-Label Period Day 8; 2 hours after dosing (n=219)	1.7 units on a scale Standard Deviation 1.03	—
Mean Pain Relief (PAR) Score During the Open-Label Period Day 8; 4 hours after dosing (n=219)	1.8 units on a scale Standard Deviation 1.02	—

SECONDARY outcome

Timeframe: 2 hours, 4 hours post-dose on Day 1, 8, 15, 22 and 28 of double-blind period

Population: Efficacy analysis set included participants received at least one dose of the study drug. Here 'n' signifies number of participants evaluable at each time point for each arm respectively.

PAR was evaluated based on 5-stage scale with a score ranging from 0 to 4, wherein, 0=no relief and 4=complete relief.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 Participants Matching placebo was given up to 4 weeks.
Mean PAR Score During the Double-Blind Period Day 8; 2 hours after dosing (n=74, 48)	1.9 units on a scale Standard Deviation 1.06	1.2 units on a scale Standard Deviation 1.08
Mean PAR Score During the Double-Blind Period Day 1; 2 hours after dosing (n=84, 89)	1.7 units on a scale Standard Deviation 1.02	1.1 units on a scale Standard Deviation 1.04
Mean PAR Score During the Double-Blind Period Day 1; 4 hours after dosing (n=84, 89)	1.8 units on a scale Standard Deviation 1.01	1.2 units on a scale Standard Deviation 1.00
Mean PAR Score During the Double-Blind Period Day 8; 4 hours after dosing (n=74, 48)	1.9 units on a scale Standard Deviation 1.01	1.4 units on a scale Standard Deviation 1.05
Mean PAR Score During the Double-Blind Period Day 15; 2 hours after dosing (n=67, 41)	2.1 units on a scale Standard Deviation 1.09	1.7 units on a scale Standard Deviation 1.11
Mean PAR Score During the Double-Blind Period Day 15; 4 hours after dosing (n=67, 41)	2.1 units on a scale Standard Deviation 1.00	1.7 units on a scale Standard Deviation 1.06
Mean PAR Score During the Double-Blind Period Day 22; 2 hours after dosing (n=63, 40)	2.1 units on a scale Standard Deviation 0.96	1.8 units on a scale Standard Deviation 1.21
Mean PAR Score During the Double-Blind Period Day 22; 4 hours after dosing (n=63, 40)	2.2 units on a scale Standard Deviation 1.00	1.8 units on a scale Standard Deviation 1.26
Mean PAR Score During the Double-Blind Period Day 28; 2 hours after dosing (n=72, 47)	2.1 units on a scale Standard Deviation 1.00	1.6 units on a scale Standard Deviation 1.26
Mean PAR Score During the Double-Blind Period Day 28; 4 hours after dosing (n=72, 47)	2.1 units on a scale Standard Deviation 1.04	1.7 units on a scale Standard Deviation 1.29

SECONDARY outcome

Timeframe: 2 hours, 4 hours post-dose on Day 1, and Day 8 of open-label period

Population: Efficacy analysis set included who received at least one dose of study medication. Here 'n' signifies number of participants evaluable for each time point.

The PRID is defined as sum of PID and PAR Scores for each participant at each evaluation time point (at 2 and 4 hours after the dosing). The overall possible score ranges for PRID is -2=worst to 7=best. The PID was calculated as PI at pre-dose on Day 1, 8 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best and PAR was evaluated based on a 5-stage scale score ranges from 0=no relief and 4=complete relief.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=277 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Pain Intensity Difference and Pain Relief Scores (PRID) During the Open-Label Period Day 1; 2 hours after dosing (n=274)	1.6 units on a scale Standard Deviation 1.39	—
Pain Intensity Difference and Pain Relief Scores (PRID) During the Open-Label Period Day 1; 4 hours after dosing (n=274)	1.9 units on a scale Standard Deviation 1.49	—
Pain Intensity Difference and Pain Relief Scores (PRID) During the Open-Label Period Day 8; 2 hours after dosing (n=219)	1.9 units on a scale Standard Deviation 1.30	—
Pain Intensity Difference and Pain Relief Scores (PRID) During the Open-Label Period Day 8; 4 hours after dosing (n=219)	2.2 units on a scale Standard Deviation 1.36	—

SECONDARY outcome

Timeframe: 2 hours, 4 hours post-dose on Day 1, 8, 15, 22 and 28 of double-blind period

Population: Efficacy analysis set included participants received at least one dose of the study drug. Here 'n' signifies number of participants evaluable at each time point for each arm respectively.

The PRID is defined as sum of PID and PAR Scores for each participant at each evaluation time point (at 2 and 4 hours after the dosing). The overall possible score range for PRID is -2=worst to 7=best. The PID was calculated as PI at pre-dose on Day 1, 8, 15, 22, 28 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8, 15, 22, 28 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best and PAR was evaluated based on a 5-stage scale score ranges from 0=no relief and 4=complete relief.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 Participants Matching placebo was given up to 4 weeks.
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period Day 1; 2 hours after dosing (n=84, 89)	1.9 units on a scale Standard Deviation 1.20	1.2 units on a scale Standard Deviation 1.19
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period Day 1; 4 hours after dosing (n=84, 89)	2.0 units on a scale Standard Deviation 1.28	1.2 units on a scale Standard Deviation 1.18
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period Day 8; 2 hours after dosing (n=74, 48)	2.1 units on a scale Standard Deviation 1.23	1.4 units on a scale Standard Deviation 1.36
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period Day 8; 4 hours after dosing (n=74, 48)	2.3 units on a scale Standard Deviation 1.22	1.6 units on a scale Standard Deviation 1.25
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period Day 15; 2 hours after dosing (n=67, 41)	2.2 units on a scale Standard Deviation 1.29	1.8 units on a scale Standard Deviation 1.39
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period Day 15; 4 hours after dosing (n=67, 41)	2.4 units on a scale Standard Deviation 1.27	1.9 units on a scale Standard Deviation 1.35
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period Day 22; 2 hours after dosing (n=63, 40)	2.3 units on a scale Standard Deviation 1.10	2.0 units on a scale Standard Deviation 1.46
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period Day 22; 4 hours after dosing (n=63, 40)	2.4 units on a scale Standard Deviation 1.24	2.1 units on a scale Standard Deviation 1.45
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period Day 28; 2 hours after dosing (n=72, 47)	2.2 units on a scale Standard Deviation 1.14	1.8 units on a scale Standard Deviation 1.52
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period Day 28; 4 hours after dosing (n=72, 47)	2.4 units on a scale Standard Deviation 1.28	1.9 units on a scale Standard Deviation 1.49

SECONDARY outcome

Timeframe: Day 1, and Day 8 of open-label period

Population: Efficacy analysis set included participants received at least one dose of the study drug. Here 'n' signifies number of participants evaluable for this outcome measure at each time point.

The SPID is defined as sum of the PID at 2 and 4 hours after dosing on each evaluation day. The overall possible score ranges for SPID is -4=worst to 6=best. The PID was calculated as PI at pre-dose on Day 1, 8 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=277 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Sum of Pain Intensity Difference (SPID) Score During the Open-Label Period Day 1 (n=274)	0.9 units on a scale Standard Deviation 1.17	—
Sum of Pain Intensity Difference (SPID) Score During the Open-Label Period Day 8 (n=219)	0.5 units on a scale Standard Deviation 0.93	—

SECONDARY outcome

Timeframe: Day 1, 8, 15, 22 and 28 of double-blind period

Population: Efficacy analysis set included participants received at least one dose of the study drug. Here 'n' signifies number of participants evaluable at each time point for each arm respectively.

The SPID is defined as sum of the PID at 2 and 4 hours after dosing on each evaluation day. The overall possible score ranges for SPID is -4=worst to 6=best. The PID was calculated as PI at pre-dose on Day 1, 8, 15, 22, 28 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8, 15, 22, 28 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 Participants Matching placebo was given up to 4 weeks.
Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period Day 1 (n=84, 89)	0.4 units on a scale Standard Deviation 0.79	0.1 units on a scale Standard Deviation 0.70
Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period Day 8 (n=74, 48)	0.5 units on a scale Standard Deviation 0.81	0.3 units on a scale Standard Deviation 0.78
Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period Day 15 (n=67, 41)	0.4 units on a scale Standard Deviation 0.76	0.4 units on a scale Standard Deviation 0.86
Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period Day 22 (n=63, 40)	0.4 units on a scale Standard Deviation 0.73	0.5 units on a scale Standard Deviation 0.78
Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period Day 28 (n=72, 47)	0.4 units on a scale Standard Deviation 0.74	0.4 units on a scale Standard Deviation 0.77

SECONDARY outcome

Timeframe: Day 1 and Day 8 of open-label period

Population: Efficacy analysis set included who received at least one dose of study drug. Here 'n' signifies number of participants evaluable for each time point.

The TOTPAR is defined as sum of PAR at 2 hours after dosing and the PAR at 4 hours after dosing on each evaluation day. Pain relief as evaluated on 5-stage scale with a score ranging from 0=no relief and 4=complete relief. Total possible score range for TOTPAR is 0=no relief to 8=complete relief.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=277 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Total Pain Relief (TOTPAR) Score During the Open-Label Period Day 1 (n=274)	2.6 units on a scale Standard Deviation 1.89	—
Total Pain Relief (TOTPAR) Score During the Open-Label Period Day 8 (n=219)	3.5 units on a scale Standard Deviation 1.95	—

SECONDARY outcome

Timeframe: Day 1, 8, 15, 22 and 28 of double-blind period

Population: Efficacy analysis set included participants received at least one dose of the study drug. Here 'n' signifies number of participants evaluable at each time point for each arm respectively.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 Participants Matching placebo was given up to 4 weeks.
Total Pain Relief (TOTPAR) Score During the Double-Blind Period Day 1 (n=84, 89)	3.5 units on a scale Standard Deviation 1.97	2.3 units on a scale Standard Deviation 2.00
Total Pain Relief (TOTPAR) Score During the Double-Blind Period Day 8 (n=74, 48)	3.8 units on a scale Standard Deviation 2.00	2.6 units on a scale Standard Deviation 2.05
Total Pain Relief (TOTPAR) Score During the Double-Blind Period Day 15 (n=67, 41)	4.1 units on a scale Standard Deviation 2.04	3.3 units on a scale Standard Deviation 2.10
Total Pain Relief (TOTPAR) Score During the Double-Blind Period Day 22 (n=63, 40)	4.3 units on a scale Standard Deviation 1.91	3.6 units on a scale Standard Deviation 2.42
Total Pain Relief (TOTPAR) Score During the Double-Blind Period Day 28 (n=72, 47)	4.2 units on a scale Standard Deviation 1.99	3.3 units on a scale Standard Deviation 2.50

SECONDARY outcome

Timeframe: Day 1, and Day 8 of open-label period

Population: Efficacy analysis set included who received at least one dose of study drug. Here 'n' signifies number of participants evaluable for each time point.

The SPRID is defined as sum of PID and PAR Scores at 2 hours and 4 hours after the dosing on each evaluation day. The overall possible score ranges for SPRID is -4=worst to 14=best. The PID was calculated as PI at pre-dose on Day 1, 8 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best and PAR was evaluated based on 5-stage scale with a score ranging from 0=no relief to 4=complete relief.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=277 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Open-Label Period Day 1 (n=274)	3.5 units on a scale Standard Deviation 2.74	—
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Open-Label Period Day 8 (n=219)	4.1 units on a scale Standard Deviation 2.50	—

SECONDARY outcome

Timeframe: Day 1, 8, 15, 22 and 28 of double-blind period

Population: Efficacy analysis set included participants received at least one dose of the study drug. Here 'n' signifies number of participants evaluable at each time point for each arm respectively.

The SPRID is defined as sum of PID and PAR Scores at 2 hours and 4 hours after the dosing on each evaluation day. The overall possible score ranges for SPRID is -4=worst to 14=best. The PID was calculated as PI at pre-dose on Day 1, 8, 15, 22, 28 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8, 15, 22, 28 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best and PAR was evaluated based on 5-stage scale with a score ranging from 0 to 4, wherein, 0=no relief and 4=complete relief.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 Participants Matching placebo was given up to 4 weeks.
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period Day 1 (n=84, 89)	3.9 units on a scale Standard Deviation 2.37	2.4 units on a scale Standard Deviation 2.30
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period Day 8 (n=74, 48)	4.3 units on a scale Standard Deviation 2.32	3.0 units on a scale Standard Deviation 2.48
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period Day 15 (n=67, 41)	4.6 units on a scale Standard Deviation 2.46	3.7 units on a scale Standard Deviation 2.61
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period Day 22 (n=63, 40)	4.7 units on a scale Standard Deviation 2.27	4.0 units on a scale Standard Deviation 2.81
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period Day 28 (n=72, 47)	4.6 units on a scale Standard Deviation 2.35	3.7 units on a scale Standard Deviation 2.90

SECONDARY outcome

Timeframe: Day 1 and Day 14 of open-label period

Population: Efficacy analysis set included who received at least one dose of study drug and had the lumbago as the target disease. Here 'n' signifies number of participants evaluable for this outcome measure at each time point.

The RDQ is self-administered measure of disability caused by low back pain and consists of 24 statements. The total score ranges from 0=no disability to 24=severe disability. The higher scores indicate greater physical disability.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=160 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Change From Baseline in Roland Morris Disability Questionnaire (RDQ) Total Score at Day 14 of Open-Label Period Day 1 (n=160)	9.1 units on a scale Standard Deviation 4.89	—
Change From Baseline in Roland Morris Disability Questionnaire (RDQ) Total Score at Day 14 of Open-Label Period Change at Day 14 (n=126)	-2.6 units on a scale Standard Deviation 3.28	—

SECONDARY outcome

Timeframe: Day 1 and Day 28 of double-blind period

Population: Efficacy analysis set included participants received at least one dose of the study drug and had the lumbago as the target disease. Here 'n' signifies number of participants evaluable at each time point for each arm respectively.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=55 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=57 Participants Matching placebo was given up to 4 weeks.
Change From Baseline in RDQ Total Score at Day 28 of Double-Blind Period Day 1 (n=55, 57)	6.5 units on a scale Standard Deviation 4.41	6.0 units on a scale Standard Deviation 4.57
Change From Baseline in RDQ Total Score at Day 28 of Double-Blind Period Change at Day 28 (n=55, 57)	-0.5 units on a scale Standard Deviation 3.08	0.8 units on a scale Standard Deviation 3.69

SECONDARY outcome

Timeframe: Day 1 and Day 14 of open-label period

Population: Efficacy analysis set included who received at least one dose of study drug and had the knee osteoarthritis as the target disease. Here 'n' signifies number of participants evaluable for this outcome measure at each time point.

The WOMAC questionnaire is an activity of daily living (ADL) indicator for Knee Osteoarthritis and designed to capture the elements of pain, stiffness, extent of obstruction to daily activities (EODA) and general index. The score for each element ranges from 0=better ADL to 10=worse ADL.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=117 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period Day 1; Pain (n=117)	4.4 units on a scale Standard Deviation 1.96	—
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period Change at Day 14; Pain (n=90)	-1.9 units on a scale Standard Deviation 1.66	—
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period Day 1; Stiffness (n=117)	4.2 units on a scale Standard Deviation 2.31	—
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period Change at Day 14; Stiffness (n=90)	-1.5 units on a scale Standard Deviation 2.09	—
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period Day 1; EODA (n=117)	3.7 units on a scale Standard Deviation 1.89	—
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period Change at Day 14; EODA (n=90)	-1.5 units on a scale Standard Deviation 1.38	—
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period Day 1; General index (n=117)	4.1 units on a scale Standard Deviation 1.82	—
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period Change at Day 14; General index (n=90)	-1.7 units on a scale Standard Deviation 1.39	—

SECONDARY outcome

Timeframe: Day 1 and Day 28 of double-blind period

The WOMAC questionnaire is an activity of daily living (ADL) indicator for knee osteoarthritis and designed to capture the elements of pain, stiffness, extent of obstruction to daily activities (EODA) and general index. The score for each element ranges from 0=better ADL to 10=worse ADL.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=39 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=36 Participants Matching placebo was given up to 4 weeks.
Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period Day 1; Pain (n=39, 36)	2.6 units on a scale Standard Deviation 1.46	2.2 units on a scale Standard Deviation 1.20
Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period Change at Day 28; Pain (n=39, 36)	-0.3 units on a scale Standard Deviation 1.02	0.5 units on a scale Standard Deviation 1.49
Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period Day 1; Stiffness (n=39, 36)	2.7 units on a scale Standard Deviation 1.94	2.4 units on a scale Standard Deviation 1.72
Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period Change at Day 28; Stiffness (n=39, 36)	-0.2 units on a scale Standard Deviation 1.33	0.2 units on a scale Standard Deviation 1.99
Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period Day 1; EODA (n=39, 36)	2.3 units on a scale Standard Deviation 1.68	1.9 units on a scale Standard Deviation 1.45
Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period Change at Day 28; EODA (n=39, 36)	-0.5 units on a scale Standard Deviation 0.58	0.4 units on a scale Standard Deviation 1.30
Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period Day 1; General index (n=39, 36)	2.5 units on a scale Standard Deviation 1.48	2.2 units on a scale Standard Deviation 1.23
Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period Change at Day 28; General index (n=39, 36)	-0.4 units on a scale Standard Deviation 0.65	0.4 units on a scale Standard Deviation 1.29

SECONDARY outcome

Timeframe: Day 1 and Day 14 of open-label period

Population: Efficacy analysis set included who received at least one dose of study drug. Here 'n' signifies number of participants evaluable for this outcome measure at each time point.

The SF-36 is a survey of participant health and quality of life. It consists of 8 sub-scales, which are the weighted sums of the questions in their section. The 8 sub-scales are: physical functioning, role-physical, role-emotional, general health, social functioning, bodily pain, vitality, mental health. Each item is scored on a scale ranging from 0-100. Higher score defines a more favorable health status or a better mental status.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=277 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) Matching placebo was given up to 4 weeks.
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Day 1; Physical functioning (n=277)	34.3 units on a scale Standard Deviation 15.23	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Change at Day 14; Physical functioning (n=216)	3.9 units on a scale Standard Deviation 10.39	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Day 1; Role-physical (n=216)	37.0 units on a scale Standard Deviation 13.62	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Change at Day 14; Role-physical (n=216)	4.3 units on a scale Standard Deviation 11.10	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Day 1; Bodily pain (n=277)	34.8 units on a scale Standard Deviation 6.59	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Change at Day 14; Bodily pain (n=216)	5.4 units on a scale Standard Deviation 7.04	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Day 1; General health (n=277)	45.4 units on a scale Standard Deviation 9.01	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Change at Day 14; General health (n=216)	2.7 units on a scale Standard Deviation 6.31	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Day 1; Vitality (n=277)	45.1 units on a scale Standard Deviation 9.43	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Change at Day 14; Vitality (n=216)	2.3 units on a scale Standard Deviation 8.10	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Day 1; Social functioning (n=277)	43.5 units on a scale Standard Deviation 12.48	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Change at Day 14; Social functioning (n=277)	2.0 units on a scale Standard Deviation 10.76	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Day 1; Role-emotional (n=277)	43.2 units on a scale Standard Deviation 12.95	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Change at Day 14; Role-emotional (n=216)	2.5 units on a scale Standard Deviation 11.36	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Day 1; Mental health (n=277)	46.8 units on a scale Standard Deviation 9.69	—
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period Change at Day 14; Mental health (n=216)	2.8 units on a scale Standard Deviation 8.59	—

SECONDARY outcome

Timeframe: Day 1 and Day 28 of double-blind period

Population: Efficacy analysis set included participants received at least one dose of the study drug. Here 'n' signifies number of participants evaluable at each time point for each arm respectively.

Outcome measures

Outcome measures
Measure	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 Participants Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 Participants Matching placebo was given up to 4 weeks.
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Day 1; Physical functioning (n=94,93)	39.0 units on a scale Standard Deviation 12.28	39.7 units on a scale Standard Deviation 13.36
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Change at Day 28; Physical functioning (n=94,93)	1.1 units on a scale Standard Deviation 8.49	-1.6 units on a scale Standard Deviation 10.03
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Day 1; Role-physical (n=94,93)	40.5 units on a scale Standard Deviation 12.84	41.8 units on a scale Standard Deviation 12.24
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Change at Day 28; Role-physical (n=94,93)	0.8 units on a scale Standard Deviation 11.87	-0.6 units on a scale Standard Deviation 9.54
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Day 1; Bodily pain (n=94,93)	41.0 units on a scale Standard Deviation 7.68	39.3 units on a scale Standard Deviation 7.27
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Change at Day 28; Bodily pain (n=94,93)	2.4 units on a scale Standard Deviation 7.24	0.3 units on a scale Standard Deviation 7.77
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Day 1; General health (n=94,93)	49.1 units on a scale Standard Deviation 9.23	48.0 units on a scale Standard Deviation 9.33
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Change at Day 28; General health (n=94,93)	0.4 units on a scale Standard Deviation 7.11	-1.2 units on a scale Standard Deviation 5.97
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Day 1; Vitality (n=94,93)	47.3 units on a scale Standard Deviation 9.58	47.4 units on a scale Standard Deviation 8.49
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Change at Day 28; Vitality (n=94,93)	3.1 units on a scale Standard Deviation 7.40	0.1 units on a scale Standard Deviation 7.51
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Day 1; Social functioning (n=94,93)	46.4 units on a scale Standard Deviation 12.68	45.7 units on a scale Standard Deviation 11.48
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Change at Day 28; Social functioning (n=94,93)	1.6 units on a scale Standard Deviation 11.32	0.4 units on a scale Standard Deviation 10.07
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Day 1; Role-emotional (n=94,93)	46.7 units on a scale Standard Deviation 11.46	45.8 units on a scale Standard Deviation 11.72
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Change at Day 28; Role-emotional (n=94,93)	0.0 units on a scale Standard Deviation 9.49	-1.0 units on a scale Standard Deviation 9.99
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Day 1; Mental health (n=94,93)	50.4 units on a scale Standard Deviation 9.14	49.6 units on a scale Standard Deviation 8.80
Change From Baseline in SF-36 at Day 28 of Double-Blind Period Change at Day 28; Mental health (n=94,93)	2.2 units on a scale Standard Deviation 7.29	-0.7 units on a scale Standard Deviation 8.17

Adverse Events

Tramadol Hydrochloride and Acetaminophen (Open-Label)

Serious events: 0 serious events

Other events: 222 other events

Deaths: 0 deaths

Tramadol Hydrochloride and Acetaminophen (Double-Blind)

Serious events: 1 serious events

Other events: 47 other events

Deaths: 0 deaths

Placebo (Double-Blind)

Serious events: 0 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tramadol Hydrochloride and Acetaminophen (Open-Label) n=277 participants at risk Fixed dose combination of tramadol 37.5 milligram (mg)/acetaminophen 325 mg, 1 or 2 tablets 4 times daily was given for one week; dose level was fixed for each participant during the second week based on analgesic efficacy and tolerability (maximum daily dose was 8 tablets).	Tramadol Hydrochloride and Acetaminophen (Double-Blind) n=94 participants at risk Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose \[number of tablets\] as that for the second week in the open-label period) was given 4 times daily up to 4 weeks.	Placebo (Double-Blind) n=93 participants at risk Matching placebo was given up to 4 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/277 • From the start of open-label period until 7 days after the last dose of study medication	1.1% 1/94 • From the start of open-label period until 7 days after the last dose of study medication	0.00% 0/93 • From the start of open-label period until 7 days after the last dose of study medication

Other adverse events

Additional Information

Medical Director

Neuroscience Department, Clinical Science Division, R&D, JANSSEN PHARMACEUTICAL. K.K.

Phone: +81-3-4411-5509

Results disclosure agreements

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

Restriction type: OTHER