Pain
Conditions
Keywords
Chronic pain, Acetoaminophen, Tramadol, Osteoarthritis of the knee, Low back pain
Brief summary
The purpose of this study is to evaluate the efficacy and safety of tramadol hydrochloride plus acetaminophen (JNS013) in participants with chronic pain accompanied by osteoarthritis (a progressive and degenerative joint disease, in which the joints become painful and stiff) of the knee or low back pain (acute or chronic pain in the lumbar or sacral regions) which cannot be controlled sufficiently with non-steriodal anti-inflammatory drugs (NSAIDs).
Detailed description
This is a multi-center (when more than one hospital or medical school team work on a medical research study), double-blind (test or experiment in which neither the person giving the treatment nor the participant knows which treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment \[with no drug in it\] that is compared in a clinical trial with a drug to test if the drug has a real effect), parallel group comparison study. The total duration of the study will be 11 weeks and consists of 4 periods; a pre-observation period (4 weeks), open-label period (2 weeks), double-blind period (4 weeks) and follow-up period (1 week). Participants will receive tramadol hydrochloride plus acetaminophen tablets orally 4 times daily for 2 weeks with no less than 4-hour intervals (up to 8 tablets per day) during the open-label period and the dose will be fixed for each participant in the latter 1 week. During the double-period participants will receive tramadol hydrochloride plus acetaminophen tablets or placebo at the same dose as used for the latter 1 week of the open-label period for up to 4 weeks. Efficacy will be primarily evaluated by number of participants with insufficient pain relief after the start of double-blind period. Participant's safety will be monitored throughout the study.
Interventions
DRUGTramadol Hydrochloride Plus Acetaminophen (Open-Label)
Fixed dose combination of tramadol 37.5 milligram (mg)/acetaminophen 325 mg, 1 or 2 tablets 4 times daily will be given for one week; dose level will be fixed for each participant during the second week based on analgesic efficacy and tolerability (maximum daily dose will be 8 tablets).
DRUGTramadol Hydrochloride Plus 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) will be given 4 times daily up to 4 weeks.
Matching placebo will be given up to 4 weeks.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with sustention of chronic pain associated with OA or LBP for at least 3 months * Participants whose pain cannot be controlled sufficiently with at least 14-day continuous treatment with identical oral NSAIDs at a usual maximum dose during 3 months prior to this study * Outpatients * Ambulatory participants without need for any supportive device or assistance during daily life
Exclusion criteria
* Participants with conditions for which opioids are contraindicated * Participants with conditions for which acetaminophen is contraindicated * Participants with history of convulsion or the possibility of convulsive seizure * Participants with concurrent, previous, or possible alcohol dependence, drug dependence, or narcotic addiction * Pregnant participants or those who may be pregnant, lactating mothers, and participants who wish pregnancy during the study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Insufficient Pain Relief After the Start of Double-Blind Period | Day 28 of double-blind period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the VAS24 Value From the Baseline at the Final Time Point of the Double-Blind Period | Day 1 and Day 28 of double-blind period | 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. |
| Mean Pain Intensity (PI) Score During Open-Label Period | Pre-dose and post-dose at 2 hours, 4 hours on Day 1, and Day 8 of open-label period | PI was evaluated on a 4-stage scale with a score ranging from 0 to 3, wherein 0=no pain and 3=severe pain. |
| Mean PI Score During Double-Blind Period | Pre-dose and post-dose at 2 hours, 4 hours on Day 1, 8, 15, 22 and 28 of double-blind period | 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. |
| Mean Pain Intensity Difference (PID) During the Open-Label Period | Pre-dose, and post-dose at 2 hours, 4 hours on Day 1, and Day 8 of open-label period | 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. |
| Mean PID During the Double-Blind Period | Pre-dose, and post-dose at 2 hours, 4 hours on Day 1, 8, 15, 22 and 28 of double-blind period | 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. |
| Mean Pain Relief (PAR) Score During the Open-Label Period | 2 hours, 4 hours post-dose on Day 1, and Day 8 of open-label period | PAR was evaluated based on 5-stage scale with a score ranging from 0 to 4, wherein, 0=no relief and 4=complete relief. |
| Mean PAR Score During the Double-Blind Period | 2 hours, 4 hours post-dose on Day 1, 8, 15, 22 and 28 of double-blind period | PAR was evaluated based on 5-stage scale with a score ranging from 0 to 4, wherein, 0=no relief and 4=complete relief. |
| Pain Intensity Difference and Pain Relief Scores (PRID) During the Open-Label Period | 2 hours, 4 hours post-dose on Day 1, and Day 8 of open-label period | 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. |
| Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | 2 hours, 4 hours post-dose on Day 1, 8, 15, 22 and 28 of double-blind period | 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. |
| Sum of Pain Intensity Difference (SPID) Score During the Open-Label Period | Day 1, and Day 8 of open-label period | 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. |
| 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 and Day 1 of double-blind period | 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. |
| Total Pain Relief (TOTPAR) Score During the Open-Label Period | Day 1 and Day 8 of open-label period | 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. |
| Total Pain Relief (TOTPAR) Score During the Double-Blind Period | Day 1, 8, 15, 22 and 28 of double-blind period | 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. |
| Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Open-Label Period | Day 1, and Day 8 of open-label period | 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. |
| Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period | Day 1, 8, 15, 22 and 28 of double-blind period | 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. |
| Change From Baseline in Roland Morris Disability Questionnaire (RDQ) Total Score at Day 14 of Open-Label Period | Day 1 and Day 14 of open-label period | 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. |
| Change From Baseline in RDQ Total Score at Day 28 of Double-Blind Period | Day 1 and Day 28 of double-blind period | 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. |
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period | Day 1 and Day 14 of open-label 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. |
| Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period | 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. |
| Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period | Day 1 and Day 14 of open-label period | 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. |
| Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Day 1 and Day 28 of double-blind period | 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. |
| Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period | Day 1, 8, 15, 22 and 28 of double-blind period | 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population 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. | 277 |
| Total | 277 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Period | Adverse Event | 0 | 3 | 2 |
| Double-Blind Period | Ineligible to participate the study | 0 | 1 | 0 |
| Double-Blind Period | Lack of Efficacy | 0 | 19 | 42 |
| Double-Blind Period | Withdrawal by Subject | 0 | 1 | 4 |
| Open-Label Period | Adverse Event | 31 | 0 | 0 |
| Open-Label Period | Failed to meet the transfer criteria | 40 | 0 | 0 |
| Open-Label Period | Physician Decision | 2 | 0 | 0 |
| Open-Label Period | Started but not treated | 42 | 0 | 0 |
| Open-Label Period | Unable to attend hospital appointments | 1 | 0 | 0 |
| Open-Label Period | Withdrawal by Subject | 16 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 57.0 years STANDARD_DEVIATION 17.5 |
| Sex: Female, Male Female | 168 Participants |
| Sex: Female, Male Male | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 222 / 277 | 47 / 94 | 44 / 93 |
| serious Total, serious adverse events | 0 / 277 | 1 / 94 | 0 / 93 |
Outcome results
Primary
Number of Participants With Insufficient Pain Relief After the Start of Double-Blind Period
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.
Time frame: Day 28 of double-blind period
Population: Efficacy analysis set included participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Number of Participants With Insufficient Pain Relief After the Start of Double-Blind Period | 20 number of participants |
| Placebo (Double-Blind) | Number of Participants With Insufficient Pain Relief After the Start of Double-Blind Period | 43 number of participants |
p-value: 0.000195% CI: [0.221, 0.641]Log Rank
Secondary
Change From Baseline in RDQ Total Score at Day 28 of Double-Blind Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Placebo (Double-Blind) | Change From Baseline in RDQ Total Score at Day 28 of Double-Blind Period | Day 1 (n=55, 57) | 6.0 units on a scale | Standard Deviation 4.57 |
| Placebo (Double-Blind) | Change From Baseline in RDQ Total Score at Day 28 of Double-Blind Period | Change at Day 28 (n=55, 57) | 0.8 units on a scale | Standard Deviation 3.69 |
Secondary
Change From Baseline in Roland Morris Disability Questionnaire (RDQ) Total Score at Day 14 of Open-Label Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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
Change From Baseline in SF-36 at Day 28 of Double-Blind Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 7.4 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Change at Day 28; Mental health (n=94,93) | -0.7 units on a scale | Standard Deviation 8.17 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Day 1; Vitality (n=94,93) | 47.4 units on a scale | Standard Deviation 8.49 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Day 1; Physical functioning (n=94,93) | 39.7 units on a scale | Standard Deviation 13.36 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Day 1; Role-emotional (n=94,93) | 45.8 units on a scale | Standard Deviation 11.72 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Change at Day 28; Physical functioning (n=94,93) | -1.6 units on a scale | Standard Deviation 10.03 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Day 1; Role-physical (n=94,93) | 41.8 units on a scale | Standard Deviation 12.24 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Change at Day 28; Vitality (n=94,93) | 0.1 units on a scale | Standard Deviation 7.51 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Change at Day 28; Role-physical (n=94,93) | -0.6 units on a scale | Standard Deviation 9.54 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Day 1; Mental health (n=94,93) | 49.6 units on a scale | Standard Deviation 8.8 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Day 1; Bodily pain (n=94,93) | 39.3 units on a scale | Standard Deviation 7.27 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Day 1; Social functioning (n=94,93) | 45.7 units on a scale | Standard Deviation 11.48 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Change at Day 28; Bodily pain (n=94,93) | 0.3 units on a scale | Standard Deviation 7.77 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Change at Day 28; Role-emotional (n=94,93) | -1.0 units on a scale | Standard Deviation 9.99 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Day 1; General health (n=94,93) | 48.0 units on a scale | Standard Deviation 9.33 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Change at Day 28; Social functioning (n=94,93) | 0.4 units on a scale | Standard Deviation 10.07 |
| Placebo (Double-Blind) | Change From Baseline in SF-36 at Day 28 of Double-Blind Period | Change at Day 28; General health (n=94,93) | -1.2 units on a scale | Standard Deviation 5.97 |
Secondary
Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 11.1 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 8.1 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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
Change From Baseline in WOMAC Questionnaire Score at 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.
Time frame: Day 1 and Day 28 of double-blind 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 at each time point for each arm respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Placebo (Double-Blind) | 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 1.29 |
| Placebo (Double-Blind) | Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period | Day 1; Pain (n=39, 36) | 2.2 units on a scale | Standard Deviation 1.2 |
| Placebo (Double-Blind) | Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period | Day 1; EODA (n=39, 36) | 1.9 units on a scale | Standard Deviation 1.45 |
| Placebo (Double-Blind) | Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period | Change at Day 28; Pain (n=39, 36) | 0.5 units on a scale | Standard Deviation 1.49 |
| Placebo (Double-Blind) | Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period | Day 1; General index (n=39, 36) | 2.2 units on a scale | Standard Deviation 1.23 |
| Placebo (Double-Blind) | Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period | Day 1; Stiffness (n=39, 36) | 2.4 units on a scale | Standard Deviation 1.72 |
| Placebo (Double-Blind) | Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period | Change at Day 28; EODA (n=39, 36) | 0.4 units on a scale | Standard Deviation 1.3 |
| Placebo (Double-Blind) | 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 1.99 |
Secondary
Change in the VAS24 Value From the Baseline at the Final Time Point of the Double-Blind Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Placebo (Double-Blind) | Change in the VAS24 Value From the Baseline at the Final Time Point of the Double-Blind Period | Day 1 | 31.18 mm | Standard Deviation 16.59 |
| Placebo (Double-Blind) | Change in the VAS24 Value From the Baseline at the Final Time Point of the Double-Blind Period | Change at Day 28 | 6.21 mm | Standard Deviation 22.5 |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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
Mean Pain Intensity Difference (PID) During the Open-Label Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 0.5 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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
Mean Pain Intensity (PI) Score During Open-Label Period
PI was evaluated on a 4-stage scale with a score ranging from 0 to 3, wherein 0=no pain and 3=severe pain.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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
Mean Pain Relief (PAR) Score During the Open-Label Period
PAR was evaluated based on 5-stage scale with a score ranging from 0 to 4, wherein, 0=no relief and 4=complete relief.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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
Mean PAR Score During the Double-Blind Period
PAR was evaluated based on 5-stage scale with a score ranging from 0 to 4, wherein, 0=no relief and 4=complete relief.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Placebo (Double-Blind) | Mean PAR Score During the Double-Blind Period | Day 22; 4 hours after dosing (n=63, 40) | 1.8 units on a scale | Standard Deviation 1.26 |
| Placebo (Double-Blind) | Mean PAR Score During the Double-Blind Period | Day 1; 2 hours after dosing (n=84, 89) | 1.1 units on a scale | Standard Deviation 1.04 |
| Placebo (Double-Blind) | Mean PAR Score During the Double-Blind Period | Day 15; 4 hours after dosing (n=67, 41) | 1.7 units on a scale | Standard Deviation 1.06 |
| Placebo (Double-Blind) | Mean PAR Score During the Double-Blind Period | Day 1; 4 hours after dosing (n=84, 89) | 1.2 units on a scale | Standard Deviation 1 |
| Placebo (Double-Blind) | Mean PAR Score During the Double-Blind Period | Day 28; 4 hours after dosing (n=72, 47) | 1.7 units on a scale | Standard Deviation 1.29 |
| Placebo (Double-Blind) | Mean PAR Score During the Double-Blind Period | Day 8; 2 hours after dosing (n=74, 48) | 1.2 units on a scale | Standard Deviation 1.08 |
| Placebo (Double-Blind) | Mean PAR Score During the Double-Blind Period | Day 22; 2 hours after dosing (n=63, 40) | 1.8 units on a scale | Standard Deviation 1.21 |
| Placebo (Double-Blind) | Mean PAR Score During the Double-Blind Period | Day 8; 4 hours after dosing (n=74, 48) | 1.4 units on a scale | Standard Deviation 1.05 |
| Placebo (Double-Blind) | Mean PAR Score During the Double-Blind Period | Day 28; 2 hours after dosing (n=72, 47) | 1.6 units on a scale | Standard Deviation 1.26 |
| Placebo (Double-Blind) | Mean PAR Score During the Double-Blind Period | Day 15; 2 hours after dosing (n=67, 41) | 1.7 units on a scale | Standard Deviation 1.11 |
Secondary
Mean PID During the Double-Blind Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Mean PID During the Double-Blind Period | Day 1; 2 hours after dosing (n=84, 89) | 0.2 units on a scale | Standard Deviation 0.4 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Mean PID During the Double-Blind Period | Day 8; 4 hours after dosing (n=74, 48) | 0.3 units on a scale | Standard Deviation 0.5 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Placebo (Double-Blind) | 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 |
| Placebo (Double-Blind) | Mean PID During the Double-Blind Period | Day 1; 2 hours after dosing (n=84, 89) | 0.1 units on a scale | Standard Deviation 0.34 |
| Placebo (Double-Blind) | Mean PID During the Double-Blind Period | Day 15; 4 hours after dosing (n=67, 41) | 0.2 units on a scale | Standard Deviation 0.51 |
| Placebo (Double-Blind) | Mean PID During the Double-Blind Period | Day 1; 4 hours after dosing (n=84, 89) | 0.1 units on a scale | Standard Deviation 0.42 |
| Placebo (Double-Blind) | Mean PID During the Double-Blind Period | Day 28; 4 hours after dosing (n=72, 47) | 0.2 units on a scale | Standard Deviation 0.43 |
| Placebo (Double-Blind) | Mean PID During the Double-Blind Period | Day 8; 2 hours after dosing (n=74, 48) | 0.1 units on a scale | Standard Deviation 0.46 |
| Placebo (Double-Blind) | Mean PID During the Double-Blind Period | Day 22; 2 hours after dosing (n=63, 40) | 0.2 units on a scale | Standard Deviation 0.42 |
| Placebo (Double-Blind) | Mean PID During the Double-Blind Period | Day 8; 4 hours after dosing (n=74, 48) | 0.2 units on a scale | Standard Deviation 0.38 |
| Placebo (Double-Blind) | Mean PID During the Double-Blind Period | Day 28; 2 hours after dosing (n=72, 47) | 0.2 units on a scale | Standard Deviation 0.41 |
| Placebo (Double-Blind) | Mean PID During the Double-Blind Period | Day 15; 2 hours after dosing (n=67, 41) | 0.2 units on a scale | Standard Deviation 0.44 |
Secondary
Mean PI Score During Double-Blind Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Mean PI Score During Double-Blind Period | Day 1; Pre-dose (n=84, 89) | 1.2 units on a scale | Standard Deviation 0.37 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Mean PI Score During Double-Blind Period | Day 22; Pre-dose (n=63, 40) | 1.1 units on a scale | Standard Deviation 0.3 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Mean PI Score During Double-Blind Period | Day 28; Pre-dose (n=72, 47) | 1.1 units on a scale | Standard Deviation 0.33 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Mean PI Score During Double-Blind Period | Day 8; Pre-dose (n=74, 48) | 1.2 units on a scale | Standard Deviation 0.39 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Mean PI Score During Double-Blind Period | Day 28; 4 hours after dosing (n=72, 47) | 0.9 units on a scale | Standard Deviation 0.5 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Mean PI Score During Double-Blind Period | Day 15; Pre-dose (n=67, 41) | 1.1 units on a scale | Standard Deviation 0.33 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 28; 4 hours after dosing (n=72, 47) | 1.0 units on a scale | Standard Deviation 0.49 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 1; Pre-dose (n=84, 89) | 1.2 units on a scale | Standard Deviation 0.37 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 1; 2 hours after dosing (n=84, 89) | 1.1 units on a scale | Standard Deviation 0.43 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 1; 4 hours after dosing (n=84, 89) | 1.1 units on a scale | Standard Deviation 0.47 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 8; Pre-dose (n=74, 48) | 1.2 units on a scale | Standard Deviation 0.42 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 8; 2 hours after dosing (n=74, 48) | 1.1 units on a scale | Standard Deviation 0.58 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 8; 4 hours after dosing (n=74, 48) | 1.1 units on a scale | Standard Deviation 0.43 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 15; Pre-dose (n=67, 41) | 1.1 units on a scale | Standard Deviation 0.33 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 15; 2 hours after dosing (n=67, 41) | 1.0 units on a scale | Standard Deviation 0.5 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 15; 4 hours after dosing (n=67, 41) | 0.9 units on a scale | Standard Deviation 0.52 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 22; Pre-dose (n=63, 40) | 1.2 units on a scale | Standard Deviation 0.38 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 22, 2 hours after dosing (n=63, 40) | 1.0 units on a scale | Standard Deviation 0.5 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 22; 4 hours after dosing (n=63, 40) | 1.0 units on a scale | Standard Deviation 0.5 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 28; Pre-dose (n=72, 47) | 1.2 units on a scale | Standard Deviation 0.41 |
| Placebo (Double-Blind) | Mean PI Score During Double-Blind Period | Day 28; 2 hours after dosing (n=72, 47) | 1.0 units on a scale | Standard Deviation 0.51 |
Secondary
Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 1.2 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 1.1 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Placebo (Double-Blind) | Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | Day 22; 4 hours after dosing (n=63, 40) | 2.1 units on a scale | Standard Deviation 1.45 |
| Placebo (Double-Blind) | Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | Day 1; 2 hours after dosing (n=84, 89) | 1.2 units on a scale | Standard Deviation 1.19 |
| Placebo (Double-Blind) | Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | Day 15; 4 hours after dosing (n=67, 41) | 1.9 units on a scale | Standard Deviation 1.35 |
| Placebo (Double-Blind) | Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | Day 1; 4 hours after dosing (n=84, 89) | 1.2 units on a scale | Standard Deviation 1.18 |
| Placebo (Double-Blind) | Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | Day 28; 4 hours after dosing (n=72, 47) | 1.9 units on a scale | Standard Deviation 1.49 |
| Placebo (Double-Blind) | Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | Day 8; 2 hours after dosing (n=74, 48) | 1.4 units on a scale | Standard Deviation 1.36 |
| Placebo (Double-Blind) | Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | Day 22; 2 hours after dosing (n=63, 40) | 2.0 units on a scale | Standard Deviation 1.46 |
| Placebo (Double-Blind) | Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | Day 8; 4 hours after dosing (n=74, 48) | 1.6 units on a scale | Standard Deviation 1.25 |
| Placebo (Double-Blind) | Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | Day 28; 2 hours after dosing (n=72, 47) | 1.8 units on a scale | Standard Deviation 1.52 |
| Placebo (Double-Blind) | Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period | Day 15; 2 hours after dosing (n=67, 41) | 1.8 units on a scale | Standard Deviation 1.39 |
Secondary
Pain Intensity Difference and Pain Relief Scores (PRID) During the Open-Label Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 1.3 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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
Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Placebo (Double-Blind) | 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 0.77 |
| Placebo (Double-Blind) | Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period | Day 1 (n=84, 89) | 0.1 units on a scale | Standard Deviation 0.7 |
| Placebo (Double-Blind) | Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period | Day 8 (n=74, 48) | 0.3 units on a scale | Standard Deviation 0.78 |
| Placebo (Double-Blind) | 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 0.86 |
| Placebo (Double-Blind) | Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period | Day 22 (n=63, 40) | 0.5 units on a scale | Standard Deviation 0.78 |
Secondary
Sum of Pain Intensity Difference (SPID) Score During the Open-Label Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Placebo (Double-Blind) | Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period | Day 28 (n=72, 47) | 3.7 units on a scale | Standard Deviation 2.9 |
| Placebo (Double-Blind) | Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period | Day 1 (n=84, 89) | 2.4 units on a scale | Standard Deviation 2.3 |
| Placebo (Double-Blind) | Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period | Day 8 (n=74, 48) | 3.0 units on a scale | Standard Deviation 2.48 |
| Placebo (Double-Blind) | Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period | Day 15 (n=67, 41) | 3.7 units on a scale | Standard Deviation 2.61 |
| Placebo (Double-Blind) | Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period | Day 22 (n=63, 40) | 4.0 units on a scale | Standard Deviation 2.81 |
Secondary
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Open-Label Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 2.5 |
Secondary
Total Pain Relief (TOTPAR) Score During the Double-Blind Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Total Pain Relief (TOTPAR) Score During the Double-Blind Period | Day 8 (n=74, 48) | 3.8 units on a scale | Standard Deviation 2 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | 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 |
| Placebo (Double-Blind) | Total Pain Relief (TOTPAR) Score During the Double-Blind Period | Day 28 (n=72, 47) | 3.3 units on a scale | Standard Deviation 2.5 |
| Placebo (Double-Blind) | Total Pain Relief (TOTPAR) Score During the Double-Blind Period | Day 1 (n=84, 89) | 2.3 units on a scale | Standard Deviation 2 |
| Placebo (Double-Blind) | Total Pain Relief (TOTPAR) Score During the Double-Blind Period | Day 8 (n=74, 48) | 2.6 units on a scale | Standard Deviation 2.05 |
| Placebo (Double-Blind) | Total Pain Relief (TOTPAR) Score During the Double-Blind Period | Day 15 (n=67, 41) | 3.3 units on a scale | Standard Deviation 2.1 |
| Placebo (Double-Blind) | Total Pain Relief (TOTPAR) Score During the Double-Blind Period | Day 22 (n=63, 40) | 3.6 units on a scale | Standard Deviation 2.42 |
Secondary
Total Pain Relief (TOTPAR) Score During the Open-Label Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Total Pain Relief (TOTPAR) Score During the Open-Label Period | Day 1 (n=274) | 2.6 units on a scale | Standard Deviation 1.89 |
| Tramadol Hydrochloride and Acetaminophen (Double-Blind) | Total Pain Relief (TOTPAR) Score During the Open-Label Period | Day 8 (n=219) | 3.5 units on a scale | Standard Deviation 1.95 |