An Open-label Extension Study With Flexible Dosing of Extended-release (ER) Tapentadol (CG5503) to Treat Patients With Moderate to Severe Chronic Pain

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess the long-term safety profile of Tapentadol (CG5503) extended release (ER) at dosages ranging from 100 to 250 mg twice a day in treating patients with moderate to severe chronic pain over a period of 1 year. The study will also assess dosage requirements over the long term; characterize adverse events and tolerability, sleep quality, and potential symptoms of withdrawal; characterize pain intensity scores and overall impression of change; and characterize patient-related health outcomes.

Detailed Description
-----------------
All patients who complete the Phase 3 pivotal trials in osteoarthritis (R331333-PAI-3008; KF5503/11) and low back pain (R331333-PAI-3011; KF5503/23) and the Phase 3 safety trial in the non-European sites (R331333-PAI-3007; KF5503/24) will be allowed to continue participation in the program by entering this trial. The trial will consist of three periods (screening, open-label treatment period, and follow-up). In the open-label treatment/maintenance period (1 year), those patients in the safety trial R331333-PAI-3007 (KF5503/24) taking open-label Tapentadol (CG5503) extended release (ER) will continue the dosage they were taking without undergoing titration. All other patients will be titrated to the minimum therapeutic dosage of Tapentadol (CG5503) extended release (ER) over 1 week. The lowest therapeutic dose allowed in the study is 100 mg twice daily, and the maximum upper dosage of Tapentadol (CG5503) extended release (ER) base is 250 mg twice daily. Downward titration (not below the minimum therapeutic dose of 100 mg twice daily) is permitted at any time using the same decrements without any time restriction. Dosages will be assessed at the scheduled (and unscheduled, if any) visits and adjustment under investigator supervision will be made as necessary. Dosage adjustments should be kept to a minimum. Intake of paracetamol/acetaminophen two 500 mg tablets daily is permitted during the titration week, and during the remainder of the open-label treatment/maintenance period up to a maximum of 7 consecutive days but no more than 14 out of 30 days. Following Week 4, all visits will be scheduled at 4-week intervals, through Week 52. The end-of-treatment visit at Week 52 will include both safety and efficacy assessments. Patients will return to the site for a follow-up visit approximately 4 days after their last dose of Tapentadol (CG5503) extended release (ER) for final safety evaluations and completion of the opioid withdrawal assessments (clinical opioid withdrawal scale, or COWS, and subjective opioid withdrawal scale, or SOWS). Patients experiencing withdrawal symptoms prior to the follow-up visit may telephone and request to be seen sooner. Additionally, the research staff at the site will telephone subjects approximately 10 to 14 days after the last dose of Tapentadol (CG5503) extended release (ER) to inquire if any adverse events have occurred since the previous visit. Tapentadol (CG5503) extended release (ER): 50, 100, 150, 200, and 250 mg orally, taken twice daily (morning and evening) for a maximum duration of 1 year.

Official Title
-----------------
Open-Label Extension, Single-Arm, Flexible-Dosing, Phase 3 Trial With CG5503 Extended-Release (ER) in Patients With Moderate to Severe Chronic Pain

Conditions
-----------------
Pain, Osteoarthritis, Low Back Pain

Intervention / Treatment
-----------------
* Drug: Tapentadol (CG5503) Extended Release (ER)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Non-lactating female subjects (Sexually active women must be postmenopausal, surgically sterile, or practicing an effective method of birth control [e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch, male partner sterilization] before entry and throughout the trial. Female patients of childbearing potential must have a negative pregnancy test at screening.) Completion of the expected double-blind treatment period of the pivotal Tapentadol (CG5503) Phase 3 trials in osteoarthritis (R331333-PAI-3008, KF5503/11) or low back pain (R331333-PAI-3011, KF5503/23), or completion of the 1-year treatment period of the safety CG5503 Phase 3 trial in the non-European sites (R331333-PAI-3007, KF5503/24) Must be willing to take Tapentadol (CG5503) extended release (ER) and the rescue medication supplied for the duration of the trial Exclusion Criteria: History of alcohol and/or drug abuse, life-long history of seizure disorder or epilepsy, any of the following within the past year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm Severe traumatic brain injury within the past 15 years Uncontrolled hypertension (repeated systolic blood pressure >160 mmHg or diastolic blood pressure >95 mmHg) Severely impaired renal function Moderately or severely impaired hepatic function Patients taking neuroleptics, monoamine oxidase inhibitors, or tricyclic antidepressants within 14 days prior to screening.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Tapentadol (CG5503) Extended Release (ER) 100 150 200 250 mg oral tablet twice daily for 52 weeks | Drug: Tapentadol (CG5503) Extended Release (ER)<br>* 100, 150, 200, 250 mg oral tablet twice daily for 52 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment-emergent Adverse Events (TEAE) | The number of subjects who reported a TEAE during the treatment period. TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 3 days after the discontinuation of the study medication. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Pain Intensity Scores at Week 52 Using the Numerical Rating Scale (NRS) | The subjects indicated the average level of pain experienced, at each study visit, over the previous 24 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, 52 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CG5503, Tapentadol, chronic non-malignant pain, osteoarthritis, lower back pain, analgesic, opioid