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

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

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).

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.

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".

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)

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.

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".

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

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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.

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A Study to Evaluate the Effectiveness and Safety of Tapentadol (R331333) Extended Release (ER) in Patients with Moderate to Severe Chronic Low Back Pain