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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Low Back Pain

Intervention / Treatment
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* Drug: tapentadol (CG5503) ER
* Drug: oxycodone CR
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>tapentadol (CG5503) ER 50 100 150 200 250 mg twice daily for 15 weeks | Drug: tapentadol (CG5503) ER<br>* 50, 100, 150, 200, 250 mg twice daily for 15 weeks<br>|
| Active Comparator: 002<br>oxycodone CR 10 20 30 40 50 mg twice daily for 15 weeks | Drug: oxycodone CR<br>* 10, 20, 30, 40, 50 mg twice daily for 15 weeks<br>|
| Placebo Comparator: 003<br>placebo matching placebo twice daily for 15 weeks | Drug: placebo<br>* matching placebo twice daily for 15 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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 | 
| 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 | 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. | 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. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low Back Pain, Chronic Pain, Pain Assessment, Tapentadol