Clinical trial NCT00449176: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Low Back Pain
Keywords: Low Back Pain
Chronic Pain
Pain Assessment
Tapentadol
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
Collaborators: name: Grünenthal GmbH
First posted: 2007-03-20
Enrollment: 981
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
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.
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change From Baseline in Brief Pain Inventory (BPI) Total Pain Score Over the Last Week of the Maintenance Period at Week 12.
timeFrame: Baseline and 12 week endpoint
measure: Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12.
timeFrame: Baseline and 12 week endpoint
measure: 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
timeFrame: Baseline and 12 week endpoint
measure: Number of Participants With Treatment Discontinuation Due to Lack of Efficacy
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in EuroQol-5® (EQ-5D) Health Status Index to Week 12
timeFrame: Baseline and 12 week endpoint
measure: Responder Analysis 50% Improvement
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
citation: Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40.