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

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Grünenthal GmbH
ClinicalTrials.gov Identifier:
NCT00486811
First received: June 14, 2007
Last updated: April 16, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Pain
Knee Osteoarthritis
Drug: Tapentadol ER (100 to 250 mg twice daily)
Drug: Matching Placebo (twice daily)
Drug: Oxycodone CR (20 to 50 mg twice daily)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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 Prolonged Release (PR) in Subjects With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee.

Resource links provided by NLM:


Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 990
Study Start Date: June 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Matching Placebo (twice daily)
Matching Placebo during 15 weeks (3 weeks titration and 12 weeks maintenance)
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.
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)
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.
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)

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).

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00486811

  Show 101 Study Locations
Sponsors and Collaborators
Grünenthal GmbH
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Principal Investigator: Alain Serrie, Dr. C.E.T.D Hôpital Lariboisière, Paris, France
  More Information

No publications provided by Grünenthal GmbH

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT00486811     History of Changes
Other Study ID Numbers: 335862, 2006-005783-67
Study First Received: June 14, 2007
Results First Received: October 25, 2010
Last Updated: April 16, 2012
Health Authority: Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: IRCCS Ospedale Maggiore di Milano
Latvia: State Agency of Medicines
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: CEBK (Centralna Ewidencja Badan Klinicznych)
Portugal: Board of Hospital Distrital de Faro
Portugal: Board of Hospital Do Divino Espirito Santo de Ponta Delgada
Portugal: Board of Hospitalda Universidade de Coimbra
Portugal: Board of Hospital des. Hospital Senhora da Oliveira Guimaraes
Portugal: Board of Hospital Central do Funchal
Portugal: Board of Instituto de Reumatologia Lisboa
Romania: National Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Grünenthal GmbH:
Osteoarthritis
Knee
Pain Assessment
CG5503 PR
Centrally acting analgesic
Placebo
Oxycodone
Chronic Pain due to knee Osteoarthritis
Tapentadol

Additional relevant MeSH terms:
Osteoarthritis, Knee
Osteoarthritis
Chronic Pain
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Oxycodone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014