A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) Extended Release (ER) in Patients With Moderate to Severe Chronic Low Back Pain
Primary Purpose
Low Back Pain
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
tapentadol (CG5503) ER
oxycodone CR
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Low Back Pain focused on measuring Low Back Pain, Chronic Pain, Pain Assessment, Tapentadol
Eligibility Criteria
Inclusion Criteria:
- Men and non-pregnant, non-lactating women having a diagnosis of Lower Back Pain (LBP) of non-malignant origin present for at least 3 months
- Patients taking analgesic medications for at least 3 months prior to screening and/or 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 numerical rater 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 judgement
- History of significant liver insufficiency
- 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 severly impaired hepatic function or with laboratory values reflecting inadequate hepatic function
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
001
002
003
Arm Description
tapentadol (CG5503) ER 50 100 150 200 250 mg twice daily for 15 weeks
oxycodone CR 10 20 30 40 50 mg twice daily for 15 weeks
placebo matching placebo twice daily for 15 weeks
Outcomes
Primary Outcome Measures
Change From Baseline of the Average Pain Intensity Based on a 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".
Secondary Outcome Measures
Change From Baseline in Brief Pain Inventory (BPI) Total Pain Score Over the Last Week of the Maintenance Period at Week 12.
Total pain score where zero equals "no pain" to ten equals "pain as bad as you can imagine" from 12 week endpoint vs baseline.
Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12.
A Sleep Questionnaire 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.
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)
Number of Participants With Treatment Discontinuation Due to Lack of Efficacy
The number of participants who discontinued due to lack of efficacy from baseline to endpoint
Change From Baseline in EuroQol-5® (EQ-5D) Health Status Index to Week 12
Change from baseline to end point in EuroQol-5 Dimension Questionnaire. A higher score indicates an improvement in health in the Health Status Index. The EuroQol-5 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.
Responder Analysis 50% Improvement
Defined by the proportion of subjects achieving at least 50% improvement from baseline in the primary endpoint of change from baseline of the average pain intensity based on the 11-point Numerical Rating Scale (NRS) at week 12. The subjects were to indicate the level of pain experienced over the previous 12 hours on an 11-point NRS where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".
Full Information
NCT ID
NCT00449176
First Posted
March 16, 2007
Last Updated
April 26, 2012
Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Collaborators
Grünenthal GmbH
1. Study Identification
Unique Protocol Identification Number
NCT00449176
Brief Title
A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) Extended Release (ER) in Patients With Moderate to Severe Chronic Low Back Pain
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 Extended-Release (ER) in Subjects With Moderate to Severe Chronic Low Back Pain
Study Type
Interventional
2. Study Status
Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Collaborators
Grünenthal GmbH
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this trial is to evaluate the effectiveness (level of pain control) and safety of orally administrated tapentadol (CG5503) Extended Release (ER) (base) at doses of 100-250 mg twice daily in patients with moderate to severe chronic pain of the lower back, in comparison with placebo and Oxycodone Controlled Release (CR).
Detailed Description
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 100-250 mg twice daily in patients with moderate to severe chronic pain of the lower back. The study is being conducted for registration and approval of tapentadol (CG5503) in the US and outside US. The trial will consist of five periods: screening (to assess eligibility), washout (3-7 days with determination of 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) in 50 mg steps to patient's optimal dose ranging between 100mg and 250mg twice a day; Oxycodone CR (controlled release) 20mg to 50mg twice a day; Placebo (no active ingredients). All doses of trial treatment will be taken orally with or without food, for a maximum timeframe of 15 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Low Back Pain
Keywords
Low Back Pain, Chronic Pain, Pain Assessment, Tapentadol
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
981 (Actual)
8. Arms, Groups, and Interventions
Arm Title
001
Arm Type
Experimental
Arm Description
tapentadol (CG5503) ER 50 100 150 200 250 mg twice daily for 15 weeks
Arm Title
002
Arm Type
Active Comparator
Arm Description
oxycodone CR 10 20 30 40 50 mg twice daily for 15 weeks
Arm Title
003
Arm Type
Placebo Comparator
Arm Description
placebo matching placebo twice daily for 15 weeks
Intervention Type
Drug
Intervention Name(s)
tapentadol (CG5503) ER
Intervention Description
50, 100, 150, 200, 250 mg twice daily for 15 weeks
Intervention Type
Drug
Intervention Name(s)
oxycodone CR
Intervention Description
10, 20, 30, 40, 50 mg twice daily for 15 weeks
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
matching placebo twice daily for 15 weeks
Primary Outcome Measure Information:
Title
Change From Baseline of the Average Pain Intensity Based on a 11-point Numerical Rating Scale (NRS) Over the Last Week of the Maintenance Period at Week 12.
Description
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".
Time Frame
Baseline and 12 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Brief Pain Inventory (BPI) Total Pain Score Over the Last Week of the Maintenance Period at Week 12.
Description
Total pain score where zero equals "no pain" to ten equals "pain as bad as you can imagine" from 12 week endpoint vs baseline.
Time Frame
Baseline and 12 week endpoint
Title
Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12.
Description
A Sleep Questionnaire 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.
Time Frame
Baseline and 12 week endpoint
Title
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
Description
Ordinal measure indicating change from start of treatment (On a scale of 7 = Very much Worse to 1 = very much improved)
Time Frame
Baseline and 12 week endpoint
Title
Number of Participants With Treatment Discontinuation Due to Lack of Efficacy
Description
The number of participants who discontinued due to lack of efficacy from baseline to endpoint
Time Frame
Baseline and 12 weeks
Title
Change From Baseline in EuroQol-5® (EQ-5D) Health Status Index to Week 12
Description
Change from baseline to end point in EuroQol-5 Dimension Questionnaire. A higher score indicates an improvement in health in the Health Status Index. The EuroQol-5 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.
Time Frame
Baseline and 12 week endpoint
Title
Responder Analysis 50% Improvement
Description
Defined by the proportion of subjects achieving at least 50% improvement from baseline in the primary endpoint of change from baseline of the average pain intensity based on the 11-point Numerical Rating Scale (NRS) at week 12. The subjects were to indicate the level of pain experienced over the previous 12 hours on an 11-point NRS where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".
Time Frame
Baseline and Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men and non-pregnant, non-lactating women having a diagnosis of Lower Back Pain (LBP) of non-malignant origin present for at least 3 months
Patients taking analgesic medications for at least 3 months prior to screening and/or 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 numerical rater 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 judgement
History of significant liver insufficiency
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 severly impaired hepatic function or with laboratory values reflecting inadequate hepatic function
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
Organizational Affiliation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
24985410
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.
Results Reference
derived
PubMed Identifier
24916058
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.
Results Reference
derived
PubMed Identifier
24353047
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.
Results Reference
derived
PubMed Identifier
23709304
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.
Results Reference
derived
PubMed Identifier
23340531
Citation
Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=68&filename=CR013399_CSR.pdf
Description
A Study to Evaluate the Effectiveness and Safety of Tapentadol (R331333) Extended Release (ER) in Patients with Moderate to Severe Chronic Low Back Pain
Learn more about this trial
A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) Extended Release (ER) in Patients With Moderate to Severe Chronic Low Back Pain
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