Osteoarthritis, KneePhase 3NCT00421928
Tapentadol (CG5503)
A Phase 3 study testing oxycodone and tapentadol (CG5503) in people with Osteoarthritis, Knee and Pain, run by Johnson & Johnson Pharmaceutical Research & Development, L.L.C..
Trial summary
The purpose of this trial is to evaluate the effectiveness (level of pain control) and safety of orally administered tapentadol (CG5503) Extended Release (ER) (base) at doses of 100-250 mg twice daily in patients with moderate to severe chronic pain due to osteoarthritis of the knee, in comparison with placebo and… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Osteoarthritis, Knee, Pain
- What is being tested?
- oxycodone and tapentadol (CG5503)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,030 participants
- Where
- No sites listed yet
- Study dates
- Jan 2007to Dec 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with osteoarthritis of the knee based on the American College of Rheumatology (ACR) criteria and functional capacity class of I-III
- patients taking analgesic medications for at least 3 months prior to screening and/or dissatisfied with their current therapy
- Patients requiring opioid treatment must be taking daily doses of opioid-based analgesic, equivalent to <160 mg of oral morphine
- baseline score of greater than or equal to 5 on an 11-point numerical rating scale, calculated as the average pain intensity during the last 3 days prior to randomization.
Who cannot join
- History of alcohol and/or drug abuse in Investigator's judgement
- history of significant liver insufficiency
- chronic hepatitis B or C, or HIV, presence of active hepatitis B or C within the past 3 months
- life-long history of seizure disorder or epilepsy
- history of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated
- uncontrolled hypertension
- patients with severely impaired renal function
- patients with moderate to severly impaired hepatic function or with laboratory values reflecting inadequate hepatic function
About this study
Official title: A Randomized Double-Blind, Placebo- and Active-Control, Parallel-arm, Phase III Trial With Controlled Adjustment of Dose to Evaluate the Efficacy and Safety of CG5503 Extended-Release (ER) in Patients With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee
The purpose of this trial is to evaluate the effectiveness (level of pain control) and safety of orally administered tapentadol (CG5503) Extended Release (ER) (base) at doses of 100-250 mg twice daily in patients with moderate to severe chronic pain due to osteoarthritis of the knee, in comparison with placebo and Oxycodone Controlled Release (CR).
Read the detailed description
The primary objective of this randomized (study medication assigned to patients by chance), double-blind (neither patient nor investigator knows the study medication) , phase III, placebo and active controlled trial is to evaluate the efficacy and safety of orally administered tapentadol (CG5503) Extended Release (ER) (base) at doses of 100-250 mg twice daily in patients with moderate to severe chronic pain from osteoarthritis (OA) of the knee. The study is being conducted for registration and approval of tapentadol (CG5503) in the US and outside the US. The trial will consist of five periods: screening (to assess eligibility) , washout (3-7 days with determination of a baseline pain intensity), titration (of dose over 3 weeks to the optimal individual level) , maintenance (investigational drug intake for 12 weeks with adjustments allowed), and follow-up (2 weeks post treatment discontinuation). The study hypothesis is that the study drug will be more effective than placebo in reducing patients pain intensity. The Secondary objectives include the collection of pharmacokinetic (related to how the body uses the drug) information for dose verification. The trial objectives will be assessed by comparing the baseline pain level to the level of week 12 of the maintenance phase. This will be done by looking at the patient's pain diary information. Titrate tapentadol (CG5503) ER (extended release) 50mg to patient's optimal dose ranging between 100mg and 250mg twice a day; Oxycodone CR (controlled release) 10mg to 50mg twice a day; Placebo (no active ingredients). All doses of trial treatment will be taken orally with approximately 120 mL of water with or without food for a maximum timeframe of 15 weeks.
- Conditions
- Osteoarthritis, Knee, Pain
- Being tested
- oxycodone, placebo, tapentadol (CG5503)
- Keywords
- Chronic Pain, Osteoarthritis, Knee, tapentadol, Pain Assessment
- Medical subject headings
- Osteoarthritis, Knee, Pain, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oxycodoneDrug
10, 20, 30, 40, 50mg twice a day (BID) during 15 weeks
placeboDrug
matching placebo twice a day (BID) during 15 weeks
tapentadol (CG5503)Drug
50, 100, 150, 200, 250mg twice a day (BID) during 15 weeks
| Study group | Role | What they receive |
|---|---|---|
| 001 | Experimental | tapentadol (CG5503) 50 100 150 200 250mg twice a day (BID) during 15 weeks Receives: Drug: tapentadol (CG5503) |
| 002 | Active comparator | oxycodone 10 20 30 40 50mg twice a day (BID) during 15 weeks Receives: Drug: oxycodone |
| 003 | Placebo comparator | placebo matching placebo twice a day (BID) during 15 weeks Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline of the Average Pain Intensity Based on an 11-point Numerical Rating Scale(NRS) Over the Last Week of the Maintenance Period at Week 12.
For this twice daily pain assessment, the subjects were to indicate the level of pain experienced over the previous 12 hours on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".
Measured: Baseline and 12 weeks (Primary endpoint is the average pain intensity score during the last week of the maintenance period).
Secondary outcomes (6)
Change From Baseline in Western Ontario McMaster Questionnaire (WOMAC) Assessing Pain, Disability and Joint Stiffness of the Knee Over the Last Week of the Maintenance Period at Week 12
Change from baseline to Week 12 of WOMAC Global Score: WOMAC is measure with a Likert ordinal scale from 0-4 with lower scores indicating lower levels of symptoms or physical disability
Measured: Baseline and 12 week endpoint
Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12.
A Sleep Questionniare addressed the following question: "How long after bedtime/lights out did you fall asleep last night (hours)?" 12 week endpoint-mean changes from baseline at endpoint for sleep latency. Decrease in time(hours) indicates improvement.
Measured: Baseline and 12 week endpoint
Percentage of Patients Who Reported Very Much Improved or Much Improved From Baseline in Patient Global Impression of Change Over the Last Week of the Maintenance Period at Week 12
Ordinal measure indicating change from start of treatment (on a scale of 7 = Very much worse to 1 = Very much improved)
Measured: Baseline and 12 week endpoint
Distribution of Time to Treatment Discontinuation Due to Lack of Efficacy
The median time to treatment discontinuation due to lack of efficacy from baseline to endpoint
Measured: Baseline to 12 weeks
Change From Baseline in EuroQol-5 (EQ-5D) Health Status Index to Week 12
Change from baseline to end point in EuroQol-5 (EQ-5D) Dimension Questionnaire. A higher score indicates an improvement in health in the Health Status Index. The EQ-5D is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead
Measured: Baseline and 12 week endpoint
Change From Baseline in Responder Analysis 50% Improvement to Week 12
Defined by the percentage of subjects achieving at least 50% improvement from baseline in the primary endpoint based on the 11-point NRS at week 12. For this twice daily pain assessment, the subjects were to indicate the level of pain experienced over the previous 12 hours on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2007 (estimated)
- Study startJan 2007
- Primary completionJul 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,030 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Grünenthal GmbH
- Investigators
- Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Study director, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00421928
- Sponsor's protocol ID
- CR013402
- Other IDs
- R331333PAI3008, KF11
- Status last verified
- Apr 2012
- First submitted
- 12 Jan 2007
- Last updated
- 18 Apr 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Etropolski M, Kuperwasser B, Flugel M, Haufel T, Lange B, Rauschkolb C, Laschewski F. Safety and tolerability of tapentadol extended release in moderate to severe chronic osteoarthritis or low back pain management: pooled analysis of randomized controlled trials. Adv Ther. 2014 Jun;31(6):604-20. doi: 10.1007/s12325-014-0128-6. Epub 2014 Jul 2.
PubMed 24985410Biondi DM, Xiang J, Etropolski M, Moskovitz B. Evaluation of blood pressure and heart rate in patients with hypertension who received tapentadol extended release for chronic pain: a post hoc, pooled data analysis. Clin Drug Investig. 2014 Aug;34(8):565-76. doi: 10.1007/s40261-014-0209-y.
PubMed 24916058Etropolski M, Lange B, Goldberg J, Steup A, Rauschkolb C. A pooled analysis of patient-specific factors and efficacy and tolerability of tapentadol extended release treatment for moderate to severe chronic pain. J Opioid Manag. 2013 Sep-Oct;9(5):343-56. doi: 10.5055/jom.2013.0177.
PubMed 24353047Merchant S, Provenzano D, Mody S, Ho KF, Etropolski M. Composite measure to assess efficacy/gastrointestinal tolerability of tapentadol ER versus oxycodone CR for chronic pain: pooled analysis of randomized studies. J Opioid Manag. 2013 Jan-Feb;9(1):51-61. doi: 10.5055/jom.2013.0147.
PubMed 23709304Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40.
PubMed 23340531
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-Blind, Placebo- and Active-Control, Parallel-arm, Phase III Trial With Controlled Adjustment of Dose to Evaluate the Efficacy and Safety of CG5503 Extended-Release (ER) in Patients With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee
- ClinicalTrials.gov ID
- NCT00421928
- Acronym / sponsor ID
- CR013402
- Conditions
- Osteoarthritis, Knee, Pain
- Keywords
- Chronic Pain, Osteoarthritis, Knee, tapentadol, Pain Assessment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,030 participants (actual)
- Lead sponsor
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.Industry (pharma, biotech, devices)
- Collaborators
- Grünenthal GmbH
- Study start
- Jan 2007
- Primary completion
- Jul 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 15 Jan 2007 (estimated)
- Results
- Posted 23 Apr 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to evaluate the effectiveness (level of pain control) and safety of orally administered tapentadol (CG5503) Extended Release (ER) (base) at doses of 100-250 mg twice daily in patients with moderate to severe chronic pain due to osteoarthritis of the knee, in comparison with placebo and Oxycodone Controlled Release (CR).
Detailed description
The primary objective of this randomized (study medication assigned to patients by chance), double-blind (neither patient nor investigator knows the study medication) , phase III, placebo and active controlled trial is to evaluate the efficacy and safety of orally administered tapentadol (CG5503) Extended Release (ER) (base) at doses of 100-250 mg twice daily in patients with moderate to severe chronic pain from osteoarthritis (OA) of the knee. The study is being conducted for registration and approval of tapentadol (CG5503) in the US and outside the US. The trial will consist of five periods: screening (to assess eligibility) , washout (3-7 days with determination of a baseline pain intensity), titration (of dose over 3 weeks to the optimal individual level) , maintenance (investigational drug intake for 12 weeks with adjustments allowed), and follow-up (2 weeks post treatment discontinuation). The study hypothesis is that the study drug will be more effective than placebo in reducing patients pain intensity. The Secondary objectives include the collection of pharmacokinetic (related to how the body uses the drug) information for dose verification. The trial objectives will be assessed by comparing the baseline pain level to the level of week 12 of the maintenance phase. This will be done by looking at the patient's pain diary information. Titrate tapentadol (CG5503) ER (extended release) 50mg to patient's optimal dose ranging between 100mg and 250mg twice a day; Oxycodone CR (controlled release) 10mg to 50mg twice a day; Placebo (no active ingredients). All doses of trial treatment will be taken orally with approximately 120 mL of water with or without food for a maximum timeframe of 15 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 001 | Experimental | Drug: tapentadol (CG5503)tapentadol (CG5503) 50 100 150 200 250mg twice a day (BID) during 15 weeks |
| 002 | Active comparator | Drug: oxycodoneoxycodone 10 20 30 40 50mg twice a day (BID) during 15 weeks |
| 003 | Placebo comparator | Drug: placeboplacebo matching placebo twice a day (BID) during 15 weeks |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients diagnosed with osteoarthritis of the knee based on the American College of Rheumatology (ACR) criteria and functional capacity class of I-III
- patients taking analgesic medications for at least 3 months prior to screening and/or dissatisfied with their current therapy
- Patients requiring opioid treatment must be taking daily doses of opioid-based analgesic, equivalent to <160 mg of oral morphine
- baseline score of greater than or equal to 5 on an 11-point numerical rating scale, calculated as the average pain intensity during the last 3 days prior to randomization.
Key exclusion criteria (8 listed)
- History of alcohol and/or drug abuse in Investigator's judgement
- history of significant liver insufficiency
- chronic hepatitis B or C, or HIV, presence of active hepatitis B or C within the past 3 months
- life-long history of seizure disorder or epilepsy
- history of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oxycodone10, 20, 30, 40, 50mg twice a day (BID) during 15 weeks | Drug | 002 |
| placebomatching placebo twice a day (BID) during 15 weeks | Drug | 003 |
| tapentadol (CG5503)50, 100, 150, 200, 250mg twice a day (BID) during 15 weeks | Drug | 001 |
Primary outcome
Change From Baseline of the Average Pain Intensity Based on an 11-point Numerical Rating Scale(NRS) Over the Last Week of the Maintenance Period at Week 12.
Time frame: Baseline and 12 weeks (Primary endpoint is the average pain intensity score during the last week of the maintenance period).
For this twice daily pain assessment, the subjects were to indicate the level of pain experienced over the previous 12 hours on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".
6 secondary outcomes
Change From Baseline in Western Ontario McMaster Questionnaire (WOMAC) Assessing Pain, Disability and Joint Stiffness of the Knee Over the Last Week of the Maintenance Period at Week 12
Time frame: Baseline and 12 week endpoint
Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12.
Time frame: Baseline and 12 week endpoint
Percentage of Patients Who Reported Very Much Improved or Much Improved From Baseline in Patient Global Impression of Change Over the Last Week of the Maintenance Period at Week 12
Time frame: Baseline and 12 week endpoint
Distribution of Time to Treatment Discontinuation Due to Lack of Efficacy
Time frame: Baseline to 12 weeks
Change From Baseline in EuroQol-5 (EQ-5D) Health Status Index to Week 12
Time frame: Baseline and 12 week endpoint
Change From Baseline in Responder Analysis 50% Improvement to Week 12
Time frame: Baseline and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24985410Etropolski M, Kuperwasser B, Flugel M, Haufel T, Lange B, Rauschkolb C, Laschewski F. Safety and tolerability of tapentadol extended release in moderate to severe chronic osteoarthritis or low back pain management: pooled analysis of randomized controlled trials. Adv Ther. 2014 Jun;31(6):604-20. doi: 10.1007/s12325-014-0128-6. Epub 2014 Jul 2.
- Derived from this study: PubMed 24916058Biondi DM, Xiang J, Etropolski M, Moskovitz B. Evaluation of blood pressure and heart rate in patients with hypertension who received tapentadol extended release for chronic pain: a post hoc, pooled data analysis. Clin Drug Investig. 2014 Aug;34(8):565-76. doi: 10.1007/s40261-014-0209-y.
- Derived from this study: PubMed 24353047Etropolski M, Lange B, Goldberg J, Steup A, Rauschkolb C. A pooled analysis of patient-specific factors and efficacy and tolerability of tapentadol extended release treatment for moderate to severe chronic pain. J Opioid Manag. 2013 Sep-Oct;9(5):343-56. doi: 10.5055/jom.2013.0177.
- Derived from this study: PubMed 23709304Merchant S, Provenzano D, Mody S, Ho KF, Etropolski M. Composite measure to assess efficacy/gastrointestinal tolerability of tapentadol ER versus oxycodone CR for chronic pain: pooled analysis of randomized studies. J Opioid Manag. 2013 Jan-Feb;9(1):51-61. doi: 10.5055/jom.2013.0147.
- Derived from this study: PubMed 23340531Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40.
- A Randomized Double-Blind, Placebo \& Active-Control, Parallel-Arm Phase 3 Study With Controlled Dose Adjustment to Evaluate the Efficacy and Safety of Tapentadol Extended-Release (ER) in Subjects With Moderate to Severe Chronic Pain Due to OA of the KneeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial study director
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing oxycodone and tapentadol (CG5503) in people with Osteoarthritis, Knee and Pain, run by Johnson & Johnson Pharmaceutical Research & Development, L.L.C..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Apr 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline of the Average Pain Intensity Based on an 11-point Numerical Rating Scale(NRS) Over the Last Week of the Maintenance Period at Week 12. (time frame: Baseline and 12 weeks (Primary endpoint is the average pain intensity score during the last week of the maintenance period).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00421928, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2012.