Low Back PainPhase 3NCT00449176

A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) Extended Release (ER) in Patients With Moderate to Severe Chronic Low Back Pain

A Phase 3 study testing tapentadol (CG5503) ER and oxycodone CR in people with Low Back Pain, run by Johnson & Johnson Pharmaceutical Research & Development, L.L.C..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Low Back Pain
What is being tested?: tapentadol (CG5503) ER and oxycodone CR
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 981 participants
Where: No sites listed yet
Study dates: Feb 2007to May 2008
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

About this study

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

Read the 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.

Conditions: Low Back Pain
Being tested: tapentadol (CG5503) ER, oxycodone CR, placebo
Keywords: Low Back Pain, Chronic Pain, Pain Assessment, Tapentadol
Medical subject headings: Low Back Pain, Chronic Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

tapentadol (CG5503) ERDrug
50, 100, 150, 200, 250 mg twice daily for 15 weeks
oxycodone CRDrug
10, 20, 30, 40, 50 mg twice daily for 15 weeks
placeboDrug
matching placebo twice daily for 15 weeks

Study groups in NCT00449176
Study group	Role	What they receive
001	Experimental	tapentadol (CG5503) ER 50 100 150 200 250 mg twice daily for 15 weeks Receives: Drug: tapentadol (CG5503) ER
002	Active comparator	oxycodone CR 10 20 30 40 50 mg twice daily for 15 weeks Receives: Drug: oxycodone CR
003	Placebo comparator	placebo matching placebo twice daily for 15 weeks Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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".
Measured: Baseline and 12 weeks

Secondary outcomes (6)

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.
Measured: Baseline and 12 week endpoint
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.
Measured: 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)
Measured: Baseline and 12 week endpoint
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
Measured: Baseline and 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 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.
Measured: Baseline and 12 week endpoint
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".
Measured: Baseline and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2007May 2008

First posted20 Mar 2007 (estimated)
Study startFeb 2007
Primary completionMay 2008
Study completionMay 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Low Back PainStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 981 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00449176
Sponsor's protocol ID: CR013399
Other IDs: R331333PAI3011
Status last verified: Apr 2012
First submitted: 16 Mar 2007
Last updated: 30 Apr 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 24985410
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.
PubMed 24916058
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.
PubMed 24353047
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.
PubMed 23709304
Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40.
PubMed 23340531

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Low Back Pain trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00449176
Acronym / sponsor ID: CR013399
Conditions: Low Back Pain
Keywords: Low Back Pain, Chronic Pain, Pain Assessment, Tapentadol
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 981 participants (actual)
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.Industry (pharma, biotech, devices)
Collaborators: Grünenthal GmbH
Study start: Feb 2007
Primary completion: May 2008 (actual)
Study completion: May 2008 (actual)
First posted: 20 Mar 2007 (estimated)
Results: Posted 24 Jun 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
001	Experimental	Drug: tapentadol (CG5503) ERtapentadol (CG5503) ER 50 100 150 200 250 mg twice daily for 15 weeks
002	Active comparator	Drug: oxycodone CRoxycodone CR 10 20 30 40 50 mg twice daily for 15 weeks
003	Placebo comparator	Drug: placeboplacebo matching placebo twice daily for 15 weeks

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
tapentadol (CG5503) ER50, 100, 150, 200, 250 mg twice daily for 15 weeks	Drug	001
oxycodone CR10, 20, 30, 40, 50 mg twice daily for 15 weeks	Drug	002
placebomatching placebo twice daily for 15 weeks	Drug	003

Primary outcome

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.
Time frame: Baseline and 12 weeks
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".

6 secondary outcomes

Change From Baseline in Brief Pain Inventory (BPI) Total Pain Score Over the Last Week of the Maintenance Period at Week 12.
Time frame: Baseline and 12 week endpoint
Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12.
Time frame: 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
Time frame: Baseline and 12 week endpoint
Number of Participants With Treatment Discontinuation Due to Lack of Efficacy
Time frame: Baseline and 12 weeks
Change From Baseline in EuroQol-5® (EQ-5D) Health Status Index to Week 12
Time frame: Baseline and 12 week endpoint
Responder Analysis 50% Improvement
Time frame: Baseline and Week 12

Results and safety

Results posted to the registry on 24 Jun 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tapentadol ER	318	166
Oxycodone CR	328	133
Placebo	319	152

Primary outcome: 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.

Time frame: Baseline and 12 weeks. Mean (Standard Deviation). Unit: scores on a scale

Measure	Tapentadol ER n = 312	Oxycodone CR n = 323	Placebo n = 316
Value	-2.9 (2.66)	-2.9 (2.52)	-2.1 (2.33)

Tapentadol ER vs Placebo: Mean Difference (Final Values): -0.8 (95% CI -1.22 to -0.47), p <0.001, ANCOVA

Population analysed: Intent To Treat (ITT) analysis set utilizing Last Observation Carried Forward (LOCF) imputation. The ITT analysis set included all randomized patients that took at least one dose of study medication following randomization. 7 patients (3 tapentadol ER, 3 oxycodone CR, 1 placebo) had no baseline pain scores therefore excluded from the analysis.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tapentadol ER	8 of ?	192 of 318 (60.4%)	Not reported
Oxycodone CR	11 of ?	240 of 328 (73.2%)	Not reported
Placebo	3 of ?	118 of 319 (37%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24985410Etropolski 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.
Derived from this study: PubMed 24916058Biondi 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.
Derived from this study: PubMed 24353047Etropolski 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.
Derived from this study: PubMed 23709304Merchant 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.
Derived from this study: PubMed 23340531Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40.
A Study to Evaluate the Effectiveness and Safety of Tapentadol (R331333) Extended Release (ER) in Patients with Moderate to Severe Chronic Low Back PainLink provided by the sponsor.

Related trials for Low Back Pain

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Effect of Lumbar Stabilization Exercises With and Without YTWL (Scapular Stabilization Exercises) on Reducing Chronic Low Back Pain and Related Disability. A Randomized Clinical Trial,
Chronic Non Specific Mechanical Low Back Pain
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial study director

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing tapentadol (CG5503) ER and oxycodone CR in people with Low Back Pain, run by Johnson & Johnson Pharmaceutical Research & Development, L.L.C..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jun 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00449176, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2012.