Osteoarthritis
Conditions
Keywords
Osteoarthritis, Celecoxib, Tramadol, Paracetamol
Brief summary
The purpose of this study is to evaluate the efficacy, safety and effects on Quality of Life (QOL) of tramadol/paracetamol (APAP) as an add-on therapy (medication taken in addition to another medication) in Filipino participants with chronic (lasting a long time) osteoarthritis (disorder, which is seen mostly in older persons, in which the joints become painful and stiff).
Detailed description
This is an open-label (all people know the identity of the intervention), randomized (study drug assigned by chance), controlled study to evaluate the efficacy, safety and effects on QOL of tramadol/APAP as an add-on therapy in Filipino participants suffering from chronic pain because of chronic osteoarthritis. Participants will be randomly assigned to 2 groups: tramadol/APAP group and non tramadol/APAP group. Participants in tramadol/APAP group will receive celecoxib 200 milligram (mg) and fixed dose combination of tramadol (37.5 mg)/APAP (325 mg) as add on therapy, while the participants in non-tramadol/APAP group will receive celecoxib 200 mg only. The total duration of the study will be 4 weeks. The participants in both the groups will be given celecoxib 200 mg once daily for 4 weeks. In addition, the participants in the tramadol/APAP group will be given add-on tramadol/APAP doses 3 times a day for 4 weeks. Participants will be asked to return for follow-up at Weeks 2 and 4. Efficacy will be assessed using 100 millimeter (mm) Visual Analog Scale (VAS) while QOL will be assessed using the Oswestry Disability Index (ODI). Participant safety will be monitored throughout the study.
Interventions
DRUGTramadol/Paracetamol (APAP)
Celecoxib 200 milligram (mg) once daily for 4 weeks and fixed dose combination of Tramadol 37.5 mg/Paracetamol 325 mg thrice daily for 4 weeks as add-on therapy.
DRUGNon-Tramadol/APAP
Celecoxib 200 mg alone once daily for 4 weeks.
Sponsors
Janssen Pharmaceutica
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with chronic osteoarthritis of knee or hip for greater than (\>) or equal to (=) 1 year (based on the American College of Rheumatology (ACR) diagnostic criteria for osteoarthritis), who are experiencing at least moderate osteoarthritis pain (\>=50 millimeter \[mm\] in 100 mm Visual Analog Scale \[VAS\]) * On any Cyclooxygenase - 2 (COX-2) inhibitors for at least 2 weeks preceding the study * Women with childbearing potential must have negative pregnancy test * Women of child bearing potential must agree to use accepted methods of contraception * Participant has signed the written informed consent form
Exclusion criteria
* Participants taking Monoamine oxydase (MAO) inhibitors, neuroleptics or drugs for seizures * Severe hepatic impairment (the impaired ability of the liver to fulfill its role in metabolism) * On maintenance tramadol and/or paracetamol(APAP) * On sedative hypnotics, short-acting analgesics, topical medications and anesthetics, and/or muscle relaxants * Pregnant, lactating or breastfeeding participants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2 | Baseline and Week 2 | VAS is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. |
| Change From Baseline in VAS-pain Score at Week 4 | Baseline and Week 4 Last Observation Carried Forward (LOCF) | VAS is a 100 mm scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. |
| Change From Baseline in Oswestry Disability Index (ODI) Score at Week 2 | Baseline and Week 2 | The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability. |
| Change From Baseline in ODI Score at Week 4 | Baseline and Week 4 (LOCF) | The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability. |
| Percentage of Participants Who Discontinued Because of Rescue Medication | Baseline up to Week 4 | Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. |
| Time to Discontinuation Because of Rescue Medication | Baseline up to Week 4 | Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. |
Countries
Philippines
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tramadol/Paracetamol (APAP) Celecoxib 200 milligram (mg) administered orally once daily for 4 weeks and fixed dose combination of tramadol 37.5 mg/paracetamol 325 mg administered orally thrice daily for 4 weeks as add-on therapy. | 242 |
| Non-Tramadol/APAP Celecoxib 200 mg administered orally once daily for 4 weeks. | 231 |
| Total | 473 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 5 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 23 | 22 |
| Overall Study | Participant needed rescue medication | 1 | 5 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Tramadol/Paracetamol (APAP) | Non-Tramadol/APAP | Total |
|---|---|---|---|
| Age Continuous | 61.991 years STANDARD_DEVIATION 12.084 | 62.40 years STANDARD_DEVIATION 12.437 | 62.19 years STANDARD_DEVIATION 12.248 |
| Sex/Gender, Customized Female | 171 participants | 177 participants | 348 participants |
| Sex/Gender, Customized Male | 69 participants | 53 participants | 122 participants |
| Sex/Gender, Customized Unknown | 2 participants | 1 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 242 | 10 / 231 |
| serious Total, serious adverse events | 1 / 242 | 1 / 231 |
Outcome results
Primary
Change From Baseline in ODI Score at Week 4
The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability.
Time frame: Baseline and Week 4 (LOCF)
Population: ITT population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment. LOCF method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol/Paracetamol (APAP) | Change From Baseline in ODI Score at Week 4 | Baseline | 58.24 units on a scale | Standard Deviation 17.034 |
| Tramadol/Paracetamol (APAP) | Change From Baseline in ODI Score at Week 4 | Change at Week 4 (LOCF) | -19.102 units on a scale | Standard Deviation 15.103 |
| Non-Tramadol/APAP | Change From Baseline in ODI Score at Week 4 | Baseline | 57.23 units on a scale | Standard Deviation 16.78 |
| Non-Tramadol/APAP | Change From Baseline in ODI Score at Week 4 | Change at Week 4 (LOCF) | -15.177 units on a scale | Standard Deviation 13.328 |
p-value: <0.05t-test, 2 sided
Primary
Change From Baseline in Oswestry Disability Index (ODI) Score at Week 2
The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability.
Time frame: Baseline and Week 2
Population: Data was not analyzed at Week 2 as time frame was too short to assess Quality of Life (QOL) by ODI score.
Primary
Change From Baseline in VAS-pain Score at Week 4
VAS is a 100 mm scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline and Week 4 Last Observation Carried Forward (LOCF)
Population: ITT population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment. LOCF method was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol/Paracetamol (APAP) | Change From Baseline in VAS-pain Score at Week 4 | -45.027 mm | Standard Deviation 19.963 |
| Non-Tramadol/APAP | Change From Baseline in VAS-pain Score at Week 4 | -34.266 mm | Standard Deviation 15.665 |
p-value: <0.05t-test, 2 sided
Primary
Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2
VAS is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline and Week 2
Population: Intent-to-treat (ITT) population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol/Paracetamol (APAP) | Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2 | Baseline | 71.86 mm | Standard Deviation 13.485 |
| Tramadol/Paracetamol (APAP) | Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2 | Change at Week 2 | -29.721 mm | Standard Deviation 16.936 |
| Non-Tramadol/APAP | Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2 | Baseline | 68.03 mm | Standard Deviation 13.77 |
| Non-Tramadol/APAP | Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2 | Change at Week 2 | -21.972 mm | Standard Deviation 12.906 |
p-value: <0.05t-test, 2 sided
Primary
Percentage of Participants Who Discontinued Because of Rescue Medication
Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation.
Time frame: Baseline up to Week 4
Population: ITT population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tramadol/Paracetamol (APAP) | Percentage of Participants Who Discontinued Because of Rescue Medication | 0.41 percentage of participants |
| Non-Tramadol/APAP | Percentage of Participants Who Discontinued Because of Rescue Medication | 2.16 percentage of participants |
Primary
Time to Discontinuation Because of Rescue Medication
Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation.
Time frame: Baseline up to Week 4
Population: Time to discontinuation because of rescue medication was not analyzed, because dates when the rescue medication was given were not properly filled out in the forms, hence the exact time to discontinuation because of rescue medication could not be determined or analyzed.