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| ID | Type | Description | Link |
|---|---|---|---|
| R331333PAI3008 | Other Identifier | Johnson & Johnson Pharmaceutical Research & Development, L.L.C. | |
| KF11 | Other Identifier | Grunenthal GMBH |
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| Name | Class |
|---|---|
| Grünenthal GmbH | INDUSTRY |
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The purpose of this trial is to evaluate the effectiveness (level of pain control) and safety of orally administered tapentadol (CG5503) Extended Release (ER) (base) at doses of 100-250 mg twice daily in patients with moderate to severe chronic pain due to osteoarthritis of the knee, in comparison with placebo and Oxycodone Controlled Release (CR).
The primary objective of this randomized (study medication assigned to patients by chance), double-blind (neither patient nor investigator knows the study medication) , phase III, placebo and active controlled trial is to evaluate the efficacy and safety of orally administered tapentadol (CG5503) Extended Release (ER) (base) at doses of 100-250 mg 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 tapentadol (CG5503) in the US and outside the US. The trial 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 post treatment discontinuation). 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 uses the drug) information for dose verification. The trial objectives will be assessed by comparing the baseline pain level to the level of week 12 of the maintenance phase. This will be done by looking at the patient's pain diary information. Titrate tapentadol (CG5503) ER (extended release) 50mg to patient's optimal dose ranging between 100mg and 250mg twice a day; Oxycodone CR (controlled release) 10mg to 50mg twice a day; Placebo (no active ingredients). All doses of trial treatment will be taken orally with approximately 120 mL of water with or without food for a maximum timeframe of 15 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 001 | Experimental | tapentadol (CG5503) 50 100 150 200 250mg twice a day (BID) during 15 weeks |
|
| 002 | Active Comparator | oxycodone 10 20 30 40 50mg twice a day (BID) during 15 weeks |
|
| 003 | Placebo Comparator | placebo matching placebo twice a day (BID) during 15 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| oxycodone | Drug | 10, 20, 30, 40, 50mg twice a day (BID) during 15 weeks |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | For this twice daily pain assessment, the subjects were to indicate the level of pain experienced over the previous 12 hours 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". | Baseline and 12 weeks (Primary endpoint is the average pain intensity score during the last week of the maintenance period). |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Western Ontario McMaster Questionnaire (WOMAC) 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 WOMAC Global Score: WOMAC is measure with a Likert ordinal scale from 0-4 with lower scores indicating lower levels of symptoms or physical disability | Baseline and 12 week endpoint |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial | Johnson & Johnson Pharmaceutical Research & Development, L.L.C. | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24985410 | Derived | 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. | |
| 24916058 |
| Label | URL |
|---|---|
| A Randomized Double-Blind, Placebo \& Active-Control, Parallel-Arm Phase 3 Study With Controlled Dose Adjustment to Evaluate the Efficacy and Safety of Tapentadol Extended-Release (ER) in Subjects With Moderate to Severe Chronic Pain Due to OA of the Knee | View source |
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The study consisted of a screening period (duration up to 14 days), a washout period (duration 3 to 7 days), a double-blind active treatment period with titration period (duration 3 weeks) and maintenance period (duration 12 weeks)
The recruitment period for this out-patient, multicenter study occurred between 07 February 2007 and 15 July 08.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tapentadol (CG5503) | Tapentadol(CG5503) extended release (ER) 100-250mg twice daily (BID) |
| FG001 | Oxycodone | oxycodone controlled release (CR)20-50mg twice daily (BID) |
| FG002 | Placebo | Matching Placebo twice daily (BID) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tapentadol (CG5503) | Tapentadol(CG5503) extended release (ER) 100-250mg twice daily (BID) |
| BG001 | Oxycodone | oxycodone controlled release (CR)20-50mg twice daily (BID) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | For this twice daily pain assessment, the subjects were to indicate the level of pain experienced over the previous 12 hours 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". | Intent-to-treat (ITT) population. Last observation carried forward (LOCF) was used to impute pain score after discontinuation | Posted | Mean | Standard Deviation | Scores on a scale | Baseline and 12 weeks (Primary endpoint is the average pain intensity score during the last week of the maintenance period). |
|
All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tapentadol (CG5503) | Tapentadol(CG5503) extended release (ER) 100-250mg twice daily (BID) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myocardial Infarction | Cardiac disorders | MedDRA (11.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Director, Clinical Leader | Johnson & Johnson Pharmaceutical Research & Development, L.L.C. | 609-730-4537 |
| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| D010146 | Pain |
| D059350 | Chronic Pain |
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D010098 | Oxycodone |
| D000077432 | Tapentadol |
| ID | Term |
|---|---|
| D003061 | Codeine |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
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| placebo |
| Drug |
matching placebo twice a day (BID) during 15 weeks |
|
| tapentadol (CG5503) | Drug | 50, 100, 150, 200, 250mg twice a day (BID) during 15 weeks |
|
| Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12. | A Sleep Questionniare addressed the following question: "How long after bedtime/lights out did you fall asleep last night (hours)?" 12 week endpoint-mean changes from baseline at endpoint for sleep latency. Decrease in time(hours) indicates improvement. | Baseline and 12 week endpoint |
| Percentage of Patients Who Reported Very Much Improved or Much Improved From Baseline in Patient Global Impression of Change Over the Last Week of the Maintenance Period at Week 12 | Ordinal measure indicating change from start of treatment (on a scale of 7 = Very much worse to 1 = Very much improved) | Baseline and 12 week endpoint |
| Distribution of 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 12 weeks |
| Change From Baseline in EuroQol-5 (EQ-5D) Health Status Index to Week 12 | Change from baseline to end point in EuroQol-5 (EQ-5D) Dimension Questionnaire. A higher score indicates an improvement in health in the Health Status Index. The EQ-5D 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 | Baseline and 12 week endpoint |
| Change From Baseline in Responder Analysis 50% Improvement to Week 12 | Defined by the percentage of subjects achieving at least 50% improvement from baseline in the primary endpoint based on the 11-point NRS at week 12. For this twice daily pain assessment, the subjects were to indicate the level of pain experienced over the previous 12 hours 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". | Baseline and Week 12 |
| 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. |
| 24353047 | Derived | 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. |
| 23709304 | Derived | 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. |
| 23340531 | Derived | Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40. |
| Withdrawal by Subject |
|
| Lack of Efficacy |
|
| Study drug non-compliant |
|
| All other |
|
| Death |
|
| BG002 | Placebo | Matching Placebo twice daily (BID) |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Oxycodone | oxycodone controlled release (CR)20-50mg twice daily (BID) |
| OG002 | Placebo | Matching Placebo twice daily (BID) |
|
|
|
| Secondary | Change From Baseline in Western Ontario McMaster Questionnaire (WOMAC) 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 WOMAC Global Score: WOMAC is measure with a Likert ordinal scale from 0-4 with lower scores indicating lower levels of symptoms or physical disability | Intent To Treat (ITT), observed cases analysis conducted, no imputation performed. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline and 12 week endpoint |
|
|
|
| Secondary | Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12. | A Sleep Questionniare addressed the following question: "How long after bedtime/lights out did you fall asleep last night (hours)?" 12 week endpoint-mean changes from baseline at endpoint for sleep latency. Decrease in time(hours) indicates improvement. | ITT | Posted | Mean | Standard Deviation | Hours | Baseline and 12 week endpoint |
|
|
|
| Secondary | Percentage of Patients Who Reported Very Much Improved or Much Improved From Baseline in Patient Global Impression of Change Over the Last Week of the Maintenance Period at Week 12 | Ordinal measure indicating change from start of treatment (on a scale of 7 = Very much worse to 1 = Very much improved) | ITT | Posted | Number | percentage of participants | Baseline and 12 week endpoint |
|
|
|
| Secondary | Distribution of Time to Treatment Discontinuation Due to Lack of Efficacy | The median time to treatment discontinuation due to lack of efficacy from baseline to endpoint | ITT: The results for median and interquartile ranges were not estimable because insufficient number of subjects discontinued due to lack of efficacy to estimate the values. | Posted | Number | median time | Baseline to 12 weeks |
|
|
| Secondary | Change From Baseline in EuroQol-5 (EQ-5D) Health Status Index to Week 12 | Change from baseline to end point in EuroQol-5 (EQ-5D) Dimension Questionnaire. A higher score indicates an improvement in health in the Health Status Index. The EQ-5D 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 | ITT | Posted | Mean | Standard Deviation | scores on a scale | Baseline and 12 week endpoint |
|
|
|
| Secondary | Change From Baseline in Responder Analysis 50% Improvement to Week 12 | Defined by the percentage of subjects achieving at least 50% improvement from baseline in the primary endpoint based on the 11-point NRS at week 12. For this twice daily pain assessment, the subjects were to indicate the level of pain experienced over the previous 12 hours 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". | ITT. Subjects who discontinued from the study were considered non-responders. | Posted | Number | Percentage of participants | Baseline and Week 12 |
|
|
|
| 4 |
| 344 |
| 200 |
| 344 |
| EG001 | Oxycodone | oxycodone controlled release (CR)20-50mg twice daily (BID) | 10 | 342 | 269 | 342 |
| EG002 | Placebo | Matching Placebo twice daily (BID) | 6 | 337 | 134 | 337 |
| Cardiac Failure Congestive | Cardiac disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Angina Pectoris | Cardiac disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Atrial Flutter | Cardiac disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Meniere's Disease | Ear and labyrinth disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (11.0) | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (11.0) | Non-systematic Assessment |
|
| Pyelonephritis Acute | Infections and infestations | MedDRA (11.0) | Non-systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Intestinal Mass | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Drug Withdrawal Syndrome | General disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Lung Cancer Metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (11.0) | Non-systematic Assessment |
|
| Embolic Stroke | Nervous system disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Confusional State | Psychiatric disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Suicidal Ideation | Psychiatric disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Renal Failure Acute | Renal and urinary disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Spinal Fusion Surgery | Surgical and medical procedures | MedDRA (11.0) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Non-systematic Assessment |
|
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| D012216 |
| Rheumatic Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000470 |
| Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |