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

Condition(s) targeted: Pain; Knee Osteoarthritis

Intervention: CG5503, centrally acting analgesic (Drug); Placebo (Drug); CG5503 (Drug); Oxycodone (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Grünenthal GmbH

Official(s) and/or principal investigator(s):
Alain Serrie, Dr., Principal Investigator, Affiliation: C.E.T.D Hôpital Lariboisière

The purpose of this study is to evaluate whether 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.

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 design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: 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.

Secondary outcome: 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.

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 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 is being conducted for registration and approval of CG5503 in Europe and outside Europe. 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 maintainence period. This will be done by looking at the patients' pain diary information (electronic diaries).

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

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 inhibitor (SNRI), tricyclic antidepressants, anticonvulsants, or anti-parkinsonian drugs, treatment with any other analgesic therapy than investigational medication or rescue medication during the trial

Site 043001, Vienna, Austria

Site 043002, Salzburg, Austria

Site 043003, Wiener Neustadt, Austria

Site 043004, Vienna, Austria

Site 043005, Innsbruck, Austria

Site 043006, Mitterdorf, Austria

Site 385001, Osijek, Croatia

Site 385002, Zagreb, Croatia

Site 385003, Karlovac, Croatia

Site 385004, Sisak, Croatia

Seite 385005, Zagreb, Croatia

Site 049001, Leipzig, Germany

Site 049002, Berlin, Germany

Site 049003, Dresden, Germany

Site 049004, Frankfurt, Germany

Site 049005, Magdeburg, Germany

Site 049006, Wiesbaden, Germany

Site 049007, Hamburg, Germany

Site 049008, Berlin, Germany

Site 049009, Schwerin, Germany

Site 049010, Berlin, Germany

Site 036002, Visegrad, Hungary

Site 036003, Budapest, Hungary

Site 036004, Kecskemet, Hungary

Site 036005, Budapest, Hungary

Site 036006, Budapest, Hungary

Site 036007, Györj, Hungary

Site 036008, Debrecen, Hungary

Site 036009, Budapest, Hungary

Site 039001, Perugia, Italy

Site 039002, Chieti, Italy

Site 039003, Milano, Italy

Site 039004, Pavia, Italy

Site 371002, Bauska, Latvia

Site 371004, Riga, Latvia

Site 371005, Riga, Latvia

Site 031003, Losser, Netherlands

Site 031004, s'Hertogenbosch, Netherlands

Site 031007, Spijkenisse, Netherlands

Site 031006, Oude Pekela, Netherlands

Site 031008, Eindhoven, Netherlands

Site 048001, Lublin, Poland

Site 048002, Wroclaw, Poland

Site 048003, Piekary Slaskie, Poland

Site 048004, Krakow, Poland

Site 048005, Konskie, Poland

Site 048006, Katowice, Poland

Site 048007, Bielsko-Biala, Poland

Site 048008, Mielec, Poland

Site 048009, Warszawa, Poland

Site 048010, Rzeszow, Poland

Site 048011, Wroclaw, Poland

Site 351001, Coimbra, Portugal

Site 351002, Ponta Delgada, Portugal

Site 351003, Faro, Portugal

Site 351004, Lisboa, Portugal

Site 351005, Guimaraes, Portugal

Sites 351008, Funchal, Portugal

Site 351009, Lisboa, Portugal

Site 040001, Bucharest, Romania

Site 040002, Bucharest, Romania

Site 040004, Campulung Muscel Arges County, Romania

Site 040005, Bucharest, Romania

Site 040006, Bucharest, Romania

Site 040007, Bucharest, Romania

Site 040008, Bucharest, Romania

Site 040009, Bucharest, Romania

Site 040010, Craiova, Dolj County, Romania

Site 040011, Bucharest, Romania

Site 421001, Kosice, Slovakia

Site 421002, Rimavska Sobota, Slovakia

Site 421003, Poprad, Slovakia

Site 421004, Presov, Slovakia

Site 421005, Banska Bystrica, Slovakia

Site 034001, Torrelavega, Spain

Site 034002, Petrer, Spain

Site 034004, Vic, Spain

Site 034005, L'Hospitalet de Llobregat, Spain

Site 034007, La roca del Valles, Spain

Site 034008, Mostoles, Spain

Site 034009, Benidorm, Spain

Site 034003, Oviedo, Spain

Site 034013, Oviedo, Spain

Site 034012, Valencia, Spain

Site 034014, Gran Canaria, Spain

Site 034015, Malaga, Spain

Site 034016, Sevilla, Spain

Site 044001, Kenton, United Kingdom

Site 044002, Chesterfield, United Kingdom

Site 044003, Solihull, United Kingdom

Site 044004, Blackpool, United Kingdom

Site 044005, Ecclesfield, United Kingdom

Site 044006, London, United Kingdom

Site 044007, Woolpit, United Kingdom

Site 044008, Falkirk, United Kingdom

Site 044009, Bradford, United Kingdom

Site 044011, London, United Kingdom

Site 044012, Birmingham, United Kingdom

Site 044013, Cardiff, United Kingdom

Site 044016, Gardens Reading, United Kingdom

Site 044018, Chorley, United Kingdom

Starting date: June 2007
Ending date: July 2008
Last updated: June 12, 2008