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PainPhase 3NCT00486811

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

A Phase 3 study testing Tapentadol ER (100 to 250 mg twice daily) and Oxycodone CR (20 to 50 mg twice daily) in people with Pain and Knee Osteoarthritis, run by Grünenthal GmbH at 100 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Pain, Knee Osteoarthritis
What is being tested?
Tapentadol ER (100 to 250 mg twice daily) and Oxycodone CR (20 to 50 mg twice daily)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
990 participants
Where
100 sitesin 13 countries
Study dates
Jun 2007to Jul 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 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.

Who cannot join

  • 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.

Trial locations and contacts

100 sites in 13 countries.

100 sites in 13 countries

United Kingdom14 sites

  • Site 044012

    Birmingham

  • Site 044004

    Blackpool

  • Site 044009

    Bradford

  • Site 044013

    Cardiff

  • Site 044002

    Chesterfield

  • Site 044018

    Chorley

  • Site 044005

    Ecclesfield

  • Site 044008

    Falkirk

  • Site 044001

    Kenton

  • Site 044006

    London

  • Site 044011

    London

  • Site 044016

    Reading

  • Site 044003

    Solihull

  • Site 044007

    Woolpit

Other trials in United Kingdom

Spain12 sites

  • Site 034002

    Alicante

  • Site 034009

    Benidorm

  • Site 034005

    L'Hospitalet de Llobregat

  • Site 034007

    La Roca del Vallès

  • Site 034015

    Málaga

  • Site 034008

    Móstoles

  • Site 034003

    Oviedo

  • Site 034013

    Oviedo

  • Site 034016

    Seville

  • Site 034001

    Torrelavega

  • Site 034012

    Valencia

  • Site 034004

    Vic

Other trials in Spain

Poland11 sites

  • Site 048007

    Bielsko-Biala

  • Site 048005

    Gmina Końskie

  • Site 048006

    Katowice

  • Site 048004

    Krakow

  • Site 048001

    Lublin

  • Site 048008

    Mielec

  • Site 048003

    Piekary Śląskie

  • Site 048010

    Rzeszów

  • Site 048009

    Warsaw

  • Site 048002

    Wroclaw

  • Site 048011

    Wroclaw

Other trials in Poland

Germany10 sites

  • Site 049002

    Berlin

  • Site 049008

    Berlin

  • Site 049010

    Berlin

  • Site 049003

    Dresden

  • Site 049004

    Frankfurt

  • Site 049007

    Hamburg

  • Site 049001

    Leipzig

  • Site 049005

    Magdeburg

  • Site 049009

    Schwerin

  • Site 049006

    Wiesbaden

Other trials in Germany

Romania10 sites

  • Site 040001

    Bucharest

  • Site 040002

    Bucharest

  • Site 040005

    Bucharest

  • Site 040006

    Bucharest

  • Site 040007

    Bucharest

  • Site 040008

    Bucharest

  • Site 040009

    Bucharest

  • Site 040011

    Bucharest

  • Site 040004

    Campulung Muscel

  • Site 040010

    Craiova

Other trials in Romania

Hungary8 sites

  • Site 036003

    Budapest

  • Site 036005

    Budapest

  • Site 036006

    Budapest

  • Site 036009

    Budapest

  • Site 036008

    Debrecen

  • Site 036004

    Kecskemét

  • Site 036007

    Kecskemét

  • Site 036002

    Visegrád

Other trials in Hungary

Portugal7 sites

  • Site 351001

    Coimbra

  • Site 351003

    Faro

  • Sites 351008

    Funchal

  • Site 351005

    Guimarães

  • Site 351004

    Lisbon

  • Site 351009

    Lisbon

  • Site 351002

    Ponta Delgada

Other trials in Portugal

Austria6 sites

  • Site 043005

    Innsbruck

  • Site 043006

    Mitterdorf

  • Site 043002

    Salzburg

  • Site 043001

    Vienna

  • Site 043004

    Vienna

  • Site 043003

    Wiener Neustadt

Other trials in Austria

Croatia5 sites

  • Site 385003

    Karlovac

  • Site 385001

    Osijek

  • Site 385004

    Sisak

  • Seite 385005

    Zagreb

  • Site 385002

    Zagreb

Other trials in Croatia

Netherlands5 sites

  • Site 031008

    Eindhoven

  • Site 031003

    Losser

  • Site 031006

    Oude Pekela

  • Site 031004

    s'Hertogenbosch

  • Site 031007

    Spijkenisse

Other trials in Netherlands

Slovakia5 sites

  • Site 421005

    Banská Bystrica

  • Site 421001

    Košice

  • Site 421003

    Poprad

  • Site 421004

    Prešov

  • Site 421002

    Rimavská Sobota

Other trials in Slovakia

Italy4 sites

  • Site 039002

    Chieti

  • Site 039003

    Milan

  • Site 039004

    Pavia

  • Site 039001

    Perugia

Other trials in Italy

Latvia3 sites

  • Site 371002

    Bauska

  • Site 371004

    Riga

  • Site 371005

    Riga

Other trials in Latvia

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 Prolonged Release (PR) in Subjects With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee.

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.

Read the 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).

Being tested
Tapentadol ER (100 to 250 mg twice daily), Matching Placebo (twice daily), Oxycodone CR (20 to 50 mg twice daily)
Keywords
Osteoarthritis, Knee, Pain Assessment, CG5503 PR, Centrally acting analgesic, Placebo, Oxycodone, Chronic Pain due to knee Osteoarthritis, Tapentadol
Medical subject headings
Pain, Osteoarthritis, Knee, Osteoarthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tapentadol ER (100 to 250 mg twice daily)Drug

    50, 100, 150, 200, 250 mg twice a day (BID) during 15 weeks (3 weeks titration and 12 weeks maintenance)

  • Matching Placebo (twice daily)Drug

    Matching Placebo during 15 weeks (3 weeks titration and 12 weeks maintenance)

  • Oxycodone CR (20 to 50 mg twice daily)Drug

    10, 20, 30, 40, 50 mg twice a day (BID) during 15 weeks (3 weeks titration and 12 weeks maintenance)

Study groups in NCT00486811
Study groupRoleWhat they receive
Matching Placebo (twice daily)Placebo comparatorThe 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.
Receives: Drug: Matching Placebo (twice daily)
Tapentadol ER (100 to 250 mg twice daily)ExperimentalThe 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.
Receives: Drug: Tapentadol ER (100 to 250 mg twice daily)
Oxycodone CR (20 to 50 mg twice daily)Active comparatorThe 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.
Receives: Drug: Oxycodone CR (20 to 50 mg twice daily)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    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.

    Measured: Change from baseline over the 12 week Maintenance Period

Secondary outcomes (11)

  1. 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.

    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.

    Measured: Change from Baseline to Week 12 of the Maintenance Period

  2. Patient Global Impression of Change

    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.

    Measured: Baseline; End of 12 week maintenance period

  3. 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 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.

    Measured: Change from baseline to week 12 of the maintenance period

  4. 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 week 12 of the maintenance period

  5. Change in the Health Survey Scores Form (SF-36)

    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.

    Measured: Change From Baseline to Week 12 of the Maintenance Period

  6. EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time

    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.

    Measured: Comparison of Baseline to Week 12 of the Maintenance Period

  7. Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period.

    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.

    Measured: Week 12 of the maintenance period compared to baseline

  8. Sleep Questionnaire: Amount of Time Slept in Hours

    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.

    Measured: Baseline to Week 12 of the maintenance period

  9. Sleep Questionnaire: Number of Awakenings During Sleep

    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.

    Measured: Week 12 of the maintenance period compared with baseline

  10. Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire)

    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.

    Measured: Week 12 of the maintenance period compared to baseline

  11. Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time

    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.

    Measured: Change from Baseline to Week 12 of the Maintenance Period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2007 (estimated)
  2. Study startJun 2007
  3. Primary completionJul 2008
  4. Study completionJul 2008

Resources

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
Double blind
Who is masked
Participant, Investigator
Enrolment
990 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00486811
Sponsor's protocol ID
335862
Other IDs
2006-005783-67
Status last verified
Oct 2019
First submitted
14 Jun 2007
Last updated
18 Oct 2019
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 24985410

  • Biondi 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 24916058

  • Etropolski 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 24353047

  • Merchant 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 23709304

  • Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40.

    PubMed 23340531

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tapentadol ER (100 to 250 mg twice daily) and Oxycodone CR (20 to 50 mg twice daily) in people with Pain and Knee Osteoarthritis, run by Grünenthal GmbH at 100 sites in 13 countries.

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 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 100 sites in United Kingdom, Spain, Poland, Germany, Romania and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

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 11 Jan 2011). 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 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). 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 NCT00486811, 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 Oct 2019.

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