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

NCT ID: NCT00486811

Last Updated: 2019-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 990 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2008-07-31

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).

Conditions

Pain; Knee Osteoarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Matching Placebo (twice daily)

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Tapentadol ER (100 to 250 mg twice daily)

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Oxycodone CR (20 to 50 mg twice daily)

Intervention Type: DRUG

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

Interventions

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)

Intervention Type: DRUG

Matching Placebo (twice daily)

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

Intervention Type: 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)

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: collaborator

Grünenthal GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alain Serrie, Dr.

Role: PRINCIPAL_INVESTIGATOR

C.E.T.D Hôpital Lariboisière, Paris, France

Locations

Site 043005

Innsbruck, , Austria

Site 043006

Mitterdorf, , Austria

Site 043002

Salzburg, , Austria

Site 043001

Vienna, , Austria

Site 043004

Vienna, , Austria

Site 043003

Wiener Neustadt, , Austria

Site 385003

Karlovac, , Croatia

Site 385001

Osijek, , Croatia

Site 385004

Sisak, , Croatia

Seite 385005

Zagreb, , Croatia

Site 385002

Zagreb, , Croatia

Site 049002

Berlin, , Germany

Site 049008

Berlin, , Germany

Site 049010

Berlin, , Germany

Site 049003

Dresden, , Germany

Site 049004

Frankfurt, , Germany

Site 049007

Hamburg, , Germany

Site 049001

Leipzig, , Germany

Site 049005

Magdeburg, , Germany

Site 049009

Schwerin, , Germany

Site 049006

Wiesbaden, , Germany

Site 036003

Budapest, , Hungary

Site 036005

Budapest, , Hungary

Site 036006

Budapest, , Hungary

Site 036009

Budapest, , Hungary

Site 036008

Debrecen, , Hungary

Site 036004

Kecskemét, , Hungary

Site 036007

Kecskemét, , Hungary

Site 036002

Visegrád, , Hungary

Site 039002

Chieti, , Italy

Site 039003

Milan, , Italy

Site 039004

Pavia, , Italy

Site 039001

Perugia, , Italy

Site 371002

Bauska, , Latvia

Site 371004

Riga, , Latvia

Site 371005

Riga, , Latvia

Site 031008

Eindhoven, , Netherlands

Site 031003

Losser, , Netherlands

Site 031006

Oude Pekela, , Netherlands

Site 031004

s'Hertogenbosch, , Netherlands

Site 031007

Spijkenisse, , Netherlands

Site 048007

Bielsko-Biala, , Poland

Site 048005

Gmina Końskie, , Poland

Site 048006

Katowice, , Poland

Site 048004

Krakow, , Poland

Site 048001

Lublin, , Poland

Site 048008

Mielec, , Poland

Site 048003

Piekary Śląskie, , Poland

Site 048010

Rzeszów, , Poland

Site 048009

Warsaw, , Poland

Site 048002

Wroclaw, , Poland

Site 048011

Wroclaw, , Poland

Site 351001

Coimbra, , Portugal

Site 351003

Faro, , Portugal

Sites 351008

Funchal, , Portugal

Site 351005

Guimarães, , Portugal

Site 351004

Lisbon, , Portugal

Site 351009

Lisbon, , Portugal

Site 351002

Ponta Delgada, , Portugal

Site 040001

Bucharest, , Romania

Site 040002

Bucharest, , Romania

Site 040005

Bucharest, , Romania

Site 040006

Bucharest, , Romania

Site 040007

Bucharest, , Romania

Site 040008

Bucharest, , Romania

Site 040009

Bucharest, , Romania

Site 040011

Bucharest, , Romania

Site 040004

Campulung Muscel, , Romania

Site 040010

Craiova, , Romania

Site 421005

Banská Bystrica, , Slovakia

Site 421001

Košice, , Slovakia

Site 421003

Poprad, , Slovakia

Site 421004

Prešov, , Slovakia

Site 421002

Rimavská Sobota, , Slovakia

Site 034002

Alicante, , Spain

Site 034009

Benidorm, , Spain

Site 034005

L'Hospitalet de Llobregat, , Spain

Site 034007

La Roca del Vallès, , Spain

Site 034015

Málaga, , Spain

Site 034008

Móstoles, , Spain

Site 034003

Oviedo, , Spain

Site 034013

Oviedo, , Spain

Site 034016

Seville, , Spain

Site 034001

Torrelavega, , Spain

Site 034012

Valencia, , Spain

Site 034004

Vic, , Spain

Site 044012

Birmingham, , United Kingdom

Site 044004

Blackpool, , United Kingdom

Site 044009

Bradford, , United Kingdom

Site 044013

Cardiff, , United Kingdom

Site 044002

Chesterfield, , United Kingdom

Site 044018

Chorley, , United Kingdom

Site 044005

Ecclesfield, , United Kingdom

Site 044008

Falkirk, , United Kingdom

Site 044001

Kenton, , United Kingdom

Site 044006

London, , United Kingdom

Site 044011

London, , United Kingdom

Site 044016

Reading, , United Kingdom

Site 044003

Solihull, , United Kingdom

Site 044007

Woolpit, , United Kingdom

Countries

Austria; Croatia; Germany; Hungary; Italy; Latvia; Netherlands; Poland; Portugal; Romania; Slovakia; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 24985410 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24916058 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24353047 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23709304 (View on PubMed)

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

Reference Type: DERIVED

PMID: 23340531 (View on PubMed)

Other Identifiers

2006-005783-67

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

335862

Identifier Type: -

Identifier Source: org_study_id