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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

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ClinicalTrials.gov Identifier: NCT00486811
Recruitment Status : Completed
First Posted : June 15, 2007
Results First Posted : January 11, 2011
Last Update Posted : October 18, 2019
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Grünenthal GmbH

Tracking Information
First Submitted Date  ICMJE June 14, 2007
First Posted Date  ICMJE June 15, 2007
Results First Submitted Date  ICMJE October 25, 2010
Results First Posted Date  ICMJE January 11, 2011
Last Update Posted Date October 18, 2019
Study Start Date  ICMJE June 2007
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2011)
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). [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 14, 2007)
Change from baseline of the average pain intensity over the last week of the Maintenance period at Week 12 or over the entire 12-week Maintenance period, depending on country requirements. [ Time Frame: 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2012)
  • 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: 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.
  • Patient Global Impression of Change [ Time Frame: 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 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 [ Time Frame: 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.
  • Time to Treatment Discontinuation Due to Lack of Efficacy [ Time Frame: Baseline to week 12 of the maintenance period ]
    The median time to treatment discontinuation due to lack of efficacy from baseline to endpoint.
  • Change in the Health Survey Scores Form (SF-36) [ Time Frame: 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.
  • EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time [ Time Frame: 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.
  • Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period. [ Time Frame: 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: Amount of Time Slept in Hours [ Time Frame: 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.
  • Sleep Questionnaire: Number of Awakenings During Sleep [ Time Frame: 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.
  • Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) [ Time Frame: 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.
  • Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2007)
Incidence rates of treatment-emergent adverse events. Changes from baseline of the Western Ontario MacMaster Questionnaire (WOMAC). Sleep Questionnaire (SQ). 11-point NRS, SF-36, EQ-5D, and others, for a maximum timeframe of 20 weeks.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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 Prolonged Release (PR) in Subjects With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee.
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Pain
  • Knee Osteoarthritis
Intervention  ICMJE
  • Drug: Tapentadol ER (100 to 250 mg twice daily)
    50, 100, 150, 200, 250 mg twice a day (BID) during 15 weeks (3 weeks titration and 12 weeks maintenance)
  • Drug: Matching Placebo (twice daily)
    Matching Placebo during 15 weeks (3 weeks titration and 12 weeks maintenance)
  • Drug: Oxycodone CR (20 to 50 mg twice daily)
    10, 20, 30, 40, 50 mg twice a day (BID) during 15 weeks (3 weeks titration and 12 weeks maintenance)
Study Arms  ICMJE
  • Placebo Comparator: 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.
    Intervention: Drug: Matching Placebo (twice daily)
  • Experimental: 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.
    Intervention: Drug: Tapentadol ER (100 to 250 mg twice daily)
  • Active Comparator: 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.
    Intervention: Drug: Oxycodone CR (20 to 50 mg twice daily)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 16, 2012)
990
Original Estimated Enrollment  ICMJE
 (submitted: June 14, 2007)
942
Actual Study Completion Date  ICMJE July 2008
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Croatia,   Germany,   Hungary,   Italy,   Latvia,   Netherlands,   Poland,   Portugal,   Romania,   Slovakia,   Spain,   United Kingdom
Removed Location Countries Czech Republic,   France
 
Administrative Information
NCT Number  ICMJE NCT00486811
Other Study ID Numbers  ICMJE 335862
2006-005783-67 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Grünenthal GmbH
Study Sponsor  ICMJE Grünenthal GmbH
Collaborators  ICMJE Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators  ICMJE
Principal Investigator: Alain Serrie, Dr. C.E.T.D Hôpital Lariboisière, Paris, France
PRS Account Grünenthal GmbH
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP