An Efficacy and Safety Study of Extended Release (ER) Tramadol Hydrochloride (HCl)/Acetaminophen in Participants With Chronic Low-Back Pain

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy and safety of extended release (ER) tramadol hydrochloride (HCl)/acetaminophen compared with placebo in participants with chronic (lasting a long time) low-back pain.

Detailed Description
-----------------
This is a double blind (a medical research study in which neither the researchers nor the participants know what treatment the participants is receiving), randomized (study drug is assigned by chance), placebo-controlled, parallel group (a medical research study comparing the response in 2 or more groups of participants receiving different interventions [treatments]) and up-titration study in participants with chronic low back pain. The study will consist of 6 visits (Day -7 to Day -1 [Visit 1], Day 1 [Visit 2], Day 3 [telephone visit], Day 8 [Visit 3], Day 15 [Visit 4] and Day 29 [Visit 5]) and 2 phases: a screening phase and treatment phase. Screening phase will be of 7 days during which, participants will receive stable dose of non-steroidal anti-inflammatory drugs (NSAIDS) or COX-2 selective inhibitors (NSAID that specifically inhibits an enzyme known as cyclooxygenase-2) for pain therapy. On the basis of average pain intensity over the last 48 hours which will be measured at baseline (at the end of screening period), participants will enter the treatment phase. Treatment phase will be of 28 days which includes 7-days of dose titration period. In treatment phase all participants will be randomly assigned to 1 of 2 possible treatments: tramadol HCl 75 milligram (mg)/acetaminophen 650 mg ER tablet treatment or the equivalent placebo (an inactive substance) treatment until study completion, Day 29. Participants will receive 1 tablet of tramadol HCl/acetaminophen ER or its equivalent placebo, once daily for 3 days. After the first 3 days, the participants will receive a telephone inquiry monitoring the occurrence of adverse events and will be given additional administration instructions for the next 4 days (1 tablet twice daily for 4 days). From Day 7, participants will receive 1 or 2 tablets twice a day depending on the degree of pain relief required. Participants will visit the center on the Day 8 (Visit 3), Day 15 (Visit 4), and Day 29 (Visit 5) after starting study drug. The efficacy will be assessed by measuring extent of reduction in pain intensity on a Visual Analog Scale (VAS). Participants' safety will be monitored throughout the study.

Official Title
-----------------
A Randomized, Placebo-Controlled, Parallel Group, Double-Blind Clinical Study to Evaluate the Efficacy and Safety of Tramadol HCl/Acetaminophen Extended Release Tablet in Subjects With Chronic Low Back Pain

Conditions
-----------------
Low Back Pain

Intervention / Treatment
-----------------
* Drug: Tramadol HCl/acetaminophen Extended Release
* Drug: Placebo
* Drug: Tramadol HCl/acetaminophen Extended Release
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants diagnosed with low back pain at least 3 months before the screening or washout period Participants who have taken a stable dose of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (drugs used for reducing inflammation and pain ) or Cyclo-Oxygenase 2 (COX-2) selective inhibitors (an anti-inflammatory drug that fights pain) from 7 days before investigational product administration, and could maintain the same dose during the period of the study Participants whose average pain intensity is more than or equal to 4.0 centimeters on Visual Analog Scale over the last 48 hours after the completion of screening Postmenopausal or surgically sterile or abstinent women or practicing a highly effective method of birth control Women with childbearing potential must have negative pregnancy test Exclusion Criteria: Participants who have taken tramadol or tramadol HCl or acetaminophen, or narcotic (strong habit-forming drug that stops pain and depresses the central nervous system) analgesic tablet within 30 days before investigational product administration Participants who have taken acetaminophen tablet within 7 days before investigational product administration Participants with tumor or infection in meninges or spinal cord Participants who have fibromyalgia (neurosensory disorder characterized by muscle pain, joint stiffness, and fatigue), reflex sympathetic dystrophy (feeling of pain associated with evidence of minor nerve injury) or causalgia (persistent, severe burning sensation of the skin), acute spinal cord compression, acute nerve root compression, severe lower extremity weakness or numbness, regional pain syndrome, meningitis (inflammation of the meninges), diskitis (nonbacterial inflammation of an intervertebral disk or disk space), back pain because of secondary infection or tumor, or pain caused by a confirmed or suspected neoplasm Participants who have taken analgesic (including local agents or anesthetics), sedative-hypnotic (e.g., diazepam), or muscle relaxant other than a stable dose of NSAIDs or COX-2 selective inhibitors within 5 times the half-life of the concerned agent before investigational product administration

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tramadol Hydrochloride (HCl)/acetaminophen<br>Participants will receive 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28. | Drug: Tramadol HCl/acetaminophen Extended Release<br>* Participants will receive 1 tablet containing 75 mg of tramadol HCl and 650 mg of acetaminophen, once daily on Days 1to 3, then 1 tablet twice daily on Days 4 to 7<br>* Other names: Ultracet Extended Relaese;Drug: Tramadol HCl/acetaminophen Extended Release<br>* Participants will receive 1 or 2 tablets containing 75 mg of tramadol HCl and 650 mg of acetaminophen, twice daily on Days 8 to 28<br>* Other names: Ultracet Extended Relaese;|
| Placebo Comparator: Placebo<br>Prticipants will receive 1 tablet matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28. | Drug: Placebo<br>* Participants will receive 1 matching placebo tablet once daily on Days 1 to 3, then 1 tablet twice daily on Days 4 to 7<br>Drug: Placebo<br>* Prticipants will receive 1 or 2 matching placebo tablet once daily on Days 1 to 3, then 1 tablet twice daily on Days 8 to 28<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Reduction in Pain Intensity | The percentage of participants with extent of reduction in pain intensity greater than or equal to 30 percent was reported. Pain intensity change rate was calculated by Visual Analog Scale (VAS) score at baseline minus VAS score at Day 29 divided by VAS score at Baseline. VAS is a 10 centimeter (cm) scale. Intensity of pain range: 0 cm=no pain to 10 cm=worst possible pain. | Baseline up to Day 29 | 
| Change From Baseline in Pain Intensity at Day 29 | Change in pain intensity experienced by participants over the last 48 hours was measured on Day 29 against Baseline with VAS. VAS is a 10 cm scale. Intensity of pain range: 0 cm=no pain to 10 cm=worst possible pain. | Baseline and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Pain Relief | Pain relief was measured in 6 stages to assess the participant's pain relief. Extent of pain relief was measured on a scale ranging from 4 to -1, where 4=complete disappearance, 3=fair relief, 2=moderate relief, 1=slight relief, 0=no change and -1=pain worsening. Relief more than 'slight relief (1)' was considered as pain relief success. | Day 8, Day 15 and Day 29 | 
| Change From Baseline in Short Form (SF)-36 Score at Day 29 | The quality of life of participants was evaluated by SF-36 Korean version questionnaire. It is composed of 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Participants answered to the questionnaire of 36 questions; and physical, social, and psychological health status were assessed. It ranges 0 to 100, and higher score indicates better quality of life, But in Reported (Rptd.) Health Transition domain higher score indicates worse quality of life. | Baseline and Day 29 | 
| Change From Baseline in Oswestry Disability Index (ODI) Korean Version Score at Day 29 | The ODI Korean version was used to assess the participant's functionality. The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). Total score is the sum of score obtained in each section and ranges from 0 to 50. A higher score represents greater disability. | Baseline and Day 29 | 
| Percentage of Participants With Investigator's Global Assessment on Investigational Product | Global assessment on investigational product was done by investigator on how well the investigational product controlled chronic (lasting a long time) low back pain. Assessment was done by categories 'Very bad (-2)' 'Bad (-1)' 'Not changed (0) 'Good (1)' and 'Very good (2)'. Assessment better than Good was considered as pain improvement success. Percentage of participants with pain improvement success is reported here. | Day 29 | 
| Percentage of Participants With Participants' Global Assessment on Investigational Product | Global assessment on investigational product was done by participants on how well the investigational product controlled chronic (lasting a long time) low back pain. Assessment was done by categories 'Very bad (-2)' 'Bad (-1)' 'Not changed (0) 'Good (1)' and 'Very good (2)'. Assessment better than Good was considered as pain improvement success. Percentage of participants with pain improvement success is reported here. | Day 29 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic low back pain, Tramadol Hydrochloride (HCl), acetaminophen