Clinical trial NCT00486811: 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: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Knee Osteoarthritis
Keywords: Osteoarthritis
Knee
Pain Assessment
CG5503 PR
Centrally acting analgesic
Placebo
Oxycodone
Chronic Pain due to knee Osteoarthritis
Tapentadol
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
First posted: 2007-06-15
Enrollment: 990
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
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).
timeFrame: Change from baseline over the 12 week Maintenance Period
Secondary outcomes:
measure: 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.
timeFrame: Change from Baseline to Week 12 of the Maintenance Period
measure: Patient Global Impression of Change
timeFrame: Baseline; End of 12 week maintenance period
measure: 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
timeFrame: Change from baseline to week 12 of the maintenance period
measure: Time to Treatment Discontinuation Due to Lack of Efficacy
timeFrame: Baseline to week 12 of the maintenance period
measure: Change in the Health Survey Scores Form (SF-36)
timeFrame: Change From Baseline to Week 12 of the Maintenance Period
measure: EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time
timeFrame: Comparison of Baseline to Week 12 of the Maintenance Period
measure: Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period.
timeFrame: Week 12 of the maintenance period compared to baseline
measure: Sleep Questionnaire: Amount of Time Slept in Hours
timeFrame: Baseline to Week 12 of the maintenance period
measure: Sleep Questionnaire: Number of Awakenings During Sleep
timeFrame: Week 12 of the maintenance period compared with baseline
measure: Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire)
timeFrame: Week 12 of the maintenance period compared to baseline
measure: Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time
timeFrame: Change from Baseline to Week 12 of the Maintenance Period
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Site 043005
city: Mitterdorf
country: Austria
facility: Site 043006
city: Salzburg
country: Austria
facility: Site 043002
city: Vienna
country: Austria
facility: Site 043001
city: Vienna
country: Austria
facility: Site 043004
city: Wiener Neustadt
country: Austria
facility: Site 043003
city: Karlovac
country: Croatia
facility: Site 385003
city: Osijek
country: Croatia
facility: Site 385001
city: Sisak
country: Croatia
facility: Site 385004
city: Zagreb
country: Croatia
facility: Seite 385005
city: Zagreb
country: Croatia
facility: Site 385002
city: Berlin
country: Germany
facility: Site 049002
city: Berlin
country: Germany
facility: Site 049008
city: Berlin
country: Germany
facility: Site 049010
city: Dresden
country: Germany
facility: Site 049003
city: Frankfurt
country: Germany
facility: Site 049004
city: Hamburg
country: Germany
facility: Site 049007
city: Leipzig
country: Germany
facility: Site 049001
city: Magdeburg
country: Germany
facility: Site 049005
city: Schwerin
country: Germany
facility: Site 049009
city: Wiesbaden
country: Germany
facility: Site 049006
city: Budapest
country: Hungary
facility: Site 036003
city: Budapest
country: Hungary
facility: Site 036005
city: Budapest
country: Hungary
facility: Site 036006
city: Budapest
country: Hungary
facility: Site 036009
city: Debrecen
country: Hungary
facility: Site 036008
city: Kecskemet
country: Hungary
facility: Site 036004
city: Kecskemét
country: Hungary
facility: Site 036007
city: Visegrad
country: Hungary
facility: Site 036002
city: Chieti
country: Italy
facility: Site 039002
city: Milano
country: Italy
facility: Site 039003
city: Pavia
country: Italy
facility: Site 039004
city: Perugia
country: Italy
facility: Site 039001
city: Bauska
country: Latvia
facility: Site 371002
city: Riga
country: Latvia
facility: Site 371004
city: Riga
country: Latvia
facility: Site 371005
city: Eindhoven
country: Netherlands
facility: Site 031008
city: Losser
country: Netherlands
facility: Site 031003
city: Oude Pekela
country: Netherlands
facility: Site 031006
city: s'Hertogenbosch
country: Netherlands
facility: Site 031004
city: Spijkenisse
country: Netherlands
facility: Site 031007
city: Bielsko-Biala
country: Poland
facility: Site 048007
city: Katowice
country: Poland
facility: Site 048006
city: Konskie
country: Poland
facility: Site 048005
city: Krakow
country: Poland
facility: Site 048004
city: Lublin
country: Poland
facility: Site 048001
city: Mielec
country: Poland
facility: Site 048008
city: Piekary Slaskie
country: Poland
facility: Site 048003
city: Rzeszow
country: Poland
facility: Site 048010
city: Warszawa
country: Poland
facility: Site 048009
city: Wroclaw
country: Poland
facility: Site 048002
city: Wroclaw
country: Poland
facility: Site 048011
city: Coimbra
country: Portugal
facility: Site 351001
city: Faro
country: Portugal
facility: Site 351003
city: Funchal
country: Portugal
facility: Sites 351008
city: Guimaraes
country: Portugal
facility: Site 351005
city: Lisboa
country: Portugal
facility: Site 351004
city: Lisboa
country: Portugal
facility: Site 351009
city: Ponta Delgada
country: Portugal
facility: Site 351002
city: Bucharest
country: Romania
facility: Site 040001
city: Bucharest
country: Romania
facility: Site 040002
city: Bucharest
country: Romania
facility: Site 040005
city: Bucharest
country: Romania
facility: Site 040006
city: Bucharest
country: Romania
facility: Site 040007
city: Bucharest
country: Romania
facility: Site 040008
city: Bucharest
country: Romania
facility: Site 040009
city: Bucharest
country: Romania
facility: Site 040011
city: Craiova
country: Romania
facility: Site 040010
city: Câmpulung
country: Romania
facility: Site 040004
city: Banska Bystrica
country: Slovakia
facility: Site 421005
city: Kosice
country: Slovakia
facility: Site 421001
city: Poprad
country: Slovakia
facility: Site 421003
city: Presov
country: Slovakia
facility: Site 421004
city: Rimavska Sobota
country: Slovakia
facility: Site 421002
city: Alicante
country: Spain
facility: Site 034002
city: Benidorm
country: Spain
facility: Site 034009
city: L'Hospitalet de Llobregat
country: Spain
facility: Site 034005
city: La roca del Valles
country: Spain
facility: Site 034007
city: Malaga
country: Spain
facility: Site 034015
city: Mostoles
country: Spain
facility: Site 034008
city: Oviedo
country: Spain
facility: Site 034003
city: Oviedo
country: Spain
facility: Site 034013
city: Sevilla
country: Spain
facility: Site 034016
city: Torrelavega
country: Spain
facility: Site 034001
city: Valencia
country: Spain
facility: Site 034012
city: Vic
country: Spain
facility: Site 034004
city: Birmingham
country: United Kingdom
facility: Site 044012
city: Blackpool
country: United Kingdom
facility: Site 044004
city: Bradford
country: United Kingdom
facility: Site 044009
city: Cardiff
country: United Kingdom
facility: Site 044013
city: Chesterfield
country: United Kingdom
facility: Site 044002
city: Chorley
country: United Kingdom
facility: Site 044018
city: Ecclesfield
country: United Kingdom
facility: Site 044005
city: Falkirk
country: United Kingdom
facility: Site 044008
city: Kenton
country: United Kingdom
facility: Site 044001
city: London
country: United Kingdom
facility: Site 044006
city: London
country: United Kingdom
facility: Site 044011
city: Reading
country: United Kingdom
facility: Site 044016
city: Solihull
country: United Kingdom
facility: Site 044003
city: Woolpit
country: United Kingdom
facility: Site 044007
Study officials:
affiliation: C.E.T.D Hôpital Lariboisière, Paris, France
name: Alain Serrie, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40.