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

Pain Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00486811
• Other study ID #: 335862
• Secondary ID: 2006-005783-67
• Status: Completed
• Phase: Phase 3
• Start date: June 2007
• Est. completion date: July 2008

Study information

• Verified date: October 2019
• Source: Grünenthal GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 990
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Pain
• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee
• Pain

Intervention

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

Locations

Country	Name	City	State
Austria	Site 043005	Innsbruck
Austria	Site 043006	Mitterdorf
Austria	Site 043002	Salzburg
Austria	Site 043001	Vienna
Austria	Site 043004	Vienna
Austria	Site 043003	Wiener Neustadt
Croatia	Site 385003	Karlovac
Croatia	Site 385001	Osijek
Croatia	Site 385004	Sisak
Croatia	Seite 385005	Zagreb
Croatia	Site 385002	Zagreb
Germany	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
Hungary	Site 036003	Budapest
Hungary	Site 036005	Budapest
Hungary	Site 036006	Budapest
Hungary	Site 036009	Budapest
Hungary	Site 036008	Debrecen
Hungary	Site 036004	Kecskemet
Hungary	Site 036007	Kecskemét
Hungary	Site 036002	Visegrad
Italy	Site 039002	Chieti
Italy	Site 039003	Milano
Italy	Site 039004	Pavia
Italy	Site 039001	Perugia
Latvia	Site 371002	Bauska
Latvia	Site 371004	Riga
Latvia	Site 371005	Riga
Netherlands	Site 031008	Eindhoven
Netherlands	Site 031003	Losser
Netherlands	Site 031006	Oude Pekela
Netherlands	Site 031004	s'Hertogenbosch
Netherlands	Site 031007	Spijkenisse
Poland	Site 048007	Bielsko-Biala
Poland	Site 048006	Katowice
Poland	Site 048005	Konskie
Poland	Site 048004	Krakow
Poland	Site 048001	Lublin
Poland	Site 048008	Mielec
Poland	Site 048003	Piekary Slaskie
Poland	Site 048010	Rzeszow
Poland	Site 048009	Warszawa
Poland	Site 048002	Wroclaw
Poland	Site 048011	Wroclaw
Portugal	Site 351001	Coimbra
Portugal	Site 351003	Faro
Portugal	Sites 351008	Funchal
Portugal	Site 351005	Guimaraes
Portugal	Site 351004	Lisboa
Portugal	Site 351009	Lisboa
Portugal	Site 351002	Ponta Delgada
Romania	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	Câmpulung
Romania	Site 040010	Craiova
Slovakia	Site 421005	Banska Bystrica
Slovakia	Site 421001	Kosice
Slovakia	Site 421003	Poprad
Slovakia	Site 421004	Presov
Slovakia	Site 421002	Rimavska Sobota
Spain	Site 034002	Alicante
Spain	Site 034009	Benidorm
Spain	Site 034005	L'Hospitalet de Llobregat
Spain	Site 034007	La roca del Valles
Spain	Site 034015	Malaga
Spain	Site 034008	Mostoles
Spain	Site 034003	Oviedo
Spain	Site 034013	Oviedo
Spain	Site 034016	Sevilla
Spain	Site 034001	Torrelavega
Spain	Site 034012	Valencia
Spain	Site 034004	Vic
United Kingdom	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

Sponsors (2)

Lead Sponsor	Collaborator
Grünenthal GmbH	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Change from baseline over the 12 week Maintenance Period
Secondary	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.	Change from Baseline to Week 12 of the Maintenance Period
Secondary	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.	Baseline; End of 12 week maintenance period
Secondary	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.	Change from baseline to week 12 of the maintenance period
Secondary	Time to Treatment Discontinuation Due to Lack of Efficacy	The median time to treatment discontinuation due to lack of efficacy from baseline to endpoint.	Baseline to week 12 of the maintenance period
Secondary	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.	Change From Baseline to Week 12 of the Maintenance Period
Secondary	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.	Comparison of Baseline to Week 12 of the Maintenance Period
Secondary	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.	Week 12 of the maintenance period compared to baseline
Secondary	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.	Baseline to Week 12 of the maintenance period
Secondary	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.	Week 12 of the maintenance period compared with baseline
Secondary	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.	Week 12 of the maintenance period compared to baseline
Secondary	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.	Change from Baseline to Week 12 of the Maintenance Period