A Study to Evaluate the Efficacy and Safety of CG5503 Prolonged Release (PR) in Subjects With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee
- Conditions
- PainKnee Osteoarthritis
- Interventions
- Drug: Matching Placebo (twice daily)
- Registration Number
- NCT00486811
- Lead Sponsor
- Grünenthal GmbH
- Brief Summary
The purpose of this study is to evaluate whether tapentadol (CG5503) prolonged-release (PR) tablets at doses of 100-250 mg twice daily provide a better pain relief in patients with moderate to severe chronic pain due to osteoarthritis of the knee than a placebo (a medication without active substance). In addition the tolerability of CG5503 PR will be assessed. One third of the patients will receive CG5503 and one third will receive placebo. For further comparison one third of the patients will receive oxycodone controlled release (CR) at doses of 20-50 mg twice daily which is an active approved pain medication. Please note that tapentadol ER (Extended Release) and tapentadol PR (Prolonged Release) are identical and used interchangeably. This is due to United States of America and European naming conventions.
- Detailed Description
This is a randomized (study medication assigned to patients by chance), double-blind (neither patient nor investigator knows which patient gets which study medication, i.e. CG5503, placebo, oxycodone), placebo and active control study. The primary objective is to evaluate the efficacy and safety of orally administered tapentadol (CG5503) prolonged-release (PR) at doses of 100-250 mg (base) twice daily in patients with moderate to severe chronic pain from osteoarthritis (OA) of the knee. The study 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 after end of treatment). 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 absorbs, distributes, changes and excretes the drug) information for dose verification. The efficacy objectives will be assessed by comparing the baseline pain level to the pain level during the maintenance period. This will be done by looking at the patients' pain diary information (electronic diaries).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 990
- 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 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 >=5 on an 11-point numeric rating scale, calculated as the average pain intensity during the last 3 days prior to randomization.
- History of alcohol and/or drug abuse in Investigator's judgment;
- 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 severely impaired hepatic function or with laboratory values reflecting inadequate hepatic function,
- Treatment with neuroleptics, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants, anticonvulsants, or anti-parkinsonian drugs, treatment with any other analgesic therapy than investigational medication or rescue medication during the trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tapentadol ER (100 to 250 mg twice daily) Tapentadol ER (100 to 250 mg twice daily) The starting dose was tapentadol ER 50 mg twice daily for 3 days. The dose was then increased to 100 mg tapentadol ER twice daily for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days. Dose decreases were allowed without time restrictions. Matching Placebo (twice daily) Matching Placebo (twice daily) The starting dose of placebo was matched with the active treatment arms taken twice daily for the first 3 days. The dose was then increased to match the active treatments for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days as in the active treatment arms. Dose decreases were allowed without time restrictions. Oxycodone CR (20 to 50 mg twice daily) Oxycodone CR (20 to 50 mg twice daily) The starting dose was oxycodone CR 10 mg twice daily for 3 days. The dose was then increased to 20 mg oxycodone CR twice daily for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days. Dose decreases were allowed without time restrictions.
- Primary Outcome Measures
Name Time Method Change From Baseline of the Average Pain Intensity Overall in the 12-week Maintenance Period of the Daily Pain Intensity on an 11-point Numeric Rating Scale (NRS). Change from baseline over the 12 week Maintenance Period For this twice daily pain assessment, the participants were required to indicate the level of pain experienced over the previous 12 hours on an 11-point Numeric Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The lower the value the less pain in the treatment group. Negative values indicate a reduction in pain.
- Secondary Outcome Measures
Name Time Method Time to Treatment Discontinuation Due to Lack of Efficacy Baseline to week 12 of the maintenance period The median time to treatment discontinuation due to lack of efficacy from baseline to endpoint.
Patient Global Impression of Change Baseline; End of 12 week maintenance period In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.
Change in the Health Survey Scores Form (SF-36) Change From Baseline to Week 12 of the Maintenance Period The Scores Form 36 (SF-36) includes several brief board questions on 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state.
Sleep Questionnaire: Amount of Time Slept in Hours Baseline to Week 12 of the maintenance period The Sleep Questionnaire addressed the following question: "How long did you sleep last night?". The mean change for the number of hours slept during the night before from baseline to 12 weeks was studied.
Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) Week 12 of the maintenance period compared to baseline The Sleep Questionnaire addressed the following question: "Please rate the overall quality of your sleep last night?" The quality of sleep at baseline and prior to completion of treatment are reported. The participant can choose one of the following options: Excellent, good, fair and poor.
Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period. Week 12 of the maintenance period compared to baseline The Sleep Questionnaire addressed the following question: "How long after bedtime/lights out did you fall asleep last night(hours)?". The mean change from baseline to 12 weeks was studied. Decrease in time, measured in hours, indicates an improvement.
Sleep Questionnaire: Number of Awakenings During Sleep Week 12 of the maintenance period compared with baseline The Sleep Questionnaire addressed the following question: "How many times did you wake up during the night?". Sleep was assessed by the subject once a week during the entire double-blind treatment period. Reported are the baseline and end of maintenance period. Generally the less the number of awakenings the better the sleep.
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. Change from Baseline to Week 12 of the Maintenance Period The twice daily pain assessments were averaged. The participants were to indicate their pain 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". The lower the value the less pain intensity.
Change From Baseline in the Western Ontario McMaster Questionnaire (WOMAC) Global Score 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 the maintenance period Change from baseline to week 12 of Western Ontario McMaster Questionnaire (WOMAC) Global Score: WOMAC is measured with a Likert ordinal scale (the participant gives one of 5 possible answers) from 0 to 4. Higher scores indicate that a symptom is bothersome and physically disabling.
EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time Comparison of Baseline to Week 12 of the Maintenance Period The participant scored the EuroQol-5. This 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. The positive values indicate that during the study the health status improved.
Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time Change from Baseline to Week 12 of the Maintenance Period The Constipation Assessment (PAC-SYM) is a 12-item self-report questionnaire that assesses the severity of symptoms of constipation. Participants are asked "How severe have each of these symptoms been in the last two weeks?" e.g. "Pain in your stomach". There are 3 subscales: 4 questions on Abdominal symptoms, 3 on rectal symptoms and 5 on stool symptoms. Responses are rated on a 5-point Likert scale ranging from 0 (absence of symptom) to 4 (very severe symptoms). If the changes in the overall or subscale scores are positive then there is a worsening in symptoms associated with constipation.
Trial Locations
- Locations (100)
Site 043002
🇦🇹Salzburg, Austria
Site 385002
🇭🇷Zagreb, Croatia
Site 043006
🇦🇹Mitterdorf, Austria
Site 385003
🇭🇷Karlovac, Croatia
Site 036009
🇭🇺Budapest, Hungary
Site 031008
🇳🇱Eindhoven, Netherlands
Site 031003
🇳🇱Losser, Netherlands
Site 048007
🇵🇱Bielsko-Biala, Poland
Site 048002
🇵🇱Wroclaw, Poland
Site 351002
🇵🇹Ponta Delgada, Portugal
Site 421004
🇸🇰Presov, Slovakia
Site 048004
🇵🇱Krakow, Poland
Site 048010
🇵🇱Rzeszow, Poland
Site 048011
🇵🇱Wroclaw, Poland
Sites 351008
🇵🇹Funchal, Portugal
Site 040006
🇷🇴Bucharest, Romania
Site 040007
🇷🇴Bucharest, Romania
Site 040009
🇷🇴Bucharest, Romania
Site 043001
🇦🇹Vienna, Austria
Site 034016
🇪🇸Sevilla, Spain
Site 036003
🇭🇺Budapest, Hungary
Site 034003
🇪🇸Oviedo, Spain
Site 036008
🇭🇺Debrecen, Hungary
Site 371002
🇱🇻Bauska, Latvia
Site 371005
🇱🇻Riga, Latvia
Site 031006
🇳🇱Oude Pekela, Netherlands
Site 048006
🇵🇱Katowice, Poland
Site 351003
🇵🇹Faro, Portugal
Site 039004
🇮🇹Pavia, Italy
Site 034013
🇪🇸Oviedo, Spain
Site 371004
🇱🇻Riga, Latvia
Site 031004
🇳🇱s'Hertogenbosch, Netherlands
Site 040001
🇷🇴Bucharest, Romania
Site 034008
🇪🇸Mostoles, Spain
Site 048005
🇵🇱Konskie, Poland
Site 040008
🇷🇴Bucharest, Romania
Site 421005
🇸🇰Banska Bystrica, Slovakia
Site 044012
🇬🇧Birmingham, United Kingdom
Site 034007
🇪🇸La roca del Valles, Spain
Site 034001
🇪🇸Torrelavega, Spain
Site 034004
🇪🇸Vic, Spain
Site 036005
🇭🇺Budapest, Hungary
Site 036006
🇭🇺Budapest, Hungary
Site 036007
🇭🇺Kecskemét, Hungary
Site 031007
🇳🇱Spijkenisse, Netherlands
Site 040005
🇷🇴Bucharest, Romania
Site 040011
🇷🇴Bucharest, Romania
Site 040004
🇷🇴Câmpulung, Romania
Site 421001
🇸🇰Kosice, Slovakia
Site 044018
🇬🇧Chorley, United Kingdom
Site 044003
🇬🇧Solihull, United Kingdom
Site 044009
🇬🇧Bradford, United Kingdom
Site 034005
🇪🇸L'Hospitalet de Llobregat, Spain
Site 044006
🇬🇧London, United Kingdom
Site 040010
🇷🇴Craiova, Romania
Site 421003
🇸🇰Poprad, Slovakia
Site 034015
🇪🇸Malaga, Spain
Site 044002
🇬🇧Chesterfield, United Kingdom
Site 044008
🇬🇧Falkirk, United Kingdom
Site 034012
🇪🇸Valencia, Spain
Site 044011
🇬🇧London, United Kingdom
Site 044004
🇬🇧Blackpool, United Kingdom
Site 044013
🇬🇧Cardiff, United Kingdom
Site 044016
🇬🇧Reading, United Kingdom
Site 039002
🇮🇹Chieti, Italy
Site 039003
🇮🇹Milano, Italy
Site 039001
🇮🇹Perugia, Italy
Site 044005
🇬🇧Ecclesfield, United Kingdom
Site 044001
🇬🇧Kenton, United Kingdom
Site 044007
🇬🇧Woolpit, United Kingdom
Site 043005
🇦🇹Innsbruck, Austria
Site 043004
🇦🇹Vienna, Austria
Site 043003
🇦🇹Wiener Neustadt, Austria
Site 385001
🇭🇷Osijek, Croatia
Seite 385005
🇭🇷Zagreb, Croatia
Site 385004
🇭🇷Sisak, Croatia
Site 049002
🇩🇪Berlin, Germany
Site 049008
🇩🇪Berlin, Germany
Site 049010
🇩🇪Berlin, Germany
Site 049001
🇩🇪Leipzig, Germany
Site 049004
🇩🇪Frankfurt, Germany
Site 049003
🇩🇪Dresden, Germany
Site 049007
🇩🇪Hamburg, Germany
Site 049005
🇩🇪Magdeburg, Germany
Site 049009
🇩🇪Schwerin, Germany
Site 049006
🇩🇪Wiesbaden, Germany
Site 036004
🇭🇺Kecskemet, Hungary
Site 036002
🇭🇺Visegrad, Hungary
Site 048001
🇵🇱Lublin, Poland
Site 048008
🇵🇱Mielec, Poland
Site 048003
🇵🇱Piekary Slaskie, Poland
Site 048009
🇵🇱Warszawa, Poland
Site 351001
🇵🇹Coimbra, Portugal
Site 351005
🇵🇹Guimaraes, Portugal
Site 351004
🇵🇹Lisboa, Portugal
Site 351009
🇵🇹Lisboa, Portugal
Site 040002
🇷🇴Bucharest, Romania
Site 421002
🇸🇰Rimavska Sobota, Slovakia
Site 034002
🇪🇸Alicante, Spain
Site 034009
🇪🇸Benidorm, Spain