Clinical trial NCT00487435: An Open-label Extension Study With Flexible Dosing of Extended-release (ER) Tapentadol (CG5503) to Treat Patients With Moderate to Severe Chronic Pain
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Osteoarthritis
Low Back Pain
Keywords: CG5503
Tapentadol
chronic non-malignant pain
osteoarthritis
lower back pain
analgesic
opioid
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
Collaborators: name: Grünenthal GmbH
First posted: 2007-06-18
Enrollment: 1166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Subjects With Treatment-emergent Adverse Events (TEAE)
timeFrame: 52 weeks
Secondary outcomes:
measure: Change From Baseline in Average Pain Intensity Scores at Week 52 Using the Numerical Rating Scale (NRS)
timeFrame: Baseline, 52 weeks
Other outcomes:
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city: Kelowna
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city: Saskatoon
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state: Saskatchewan
city: Halifax
country: Canada
city: Christchurch
country: New Zealand
city: Tauranga
country: New Zealand
city: Wellington
country: New Zealand
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: Buynak R, Rappaport SA, Rod K, Arsenault P, Heisig F, Rauschkolb C, Etropolski M. Long-term Safety and Efficacy of Tapentadol Extended Release Following up to 2 Years of Treatment in Patients With Moderate to Severe, Chronic Pain: Results of an Open-label Extension Trial. Clin Ther. 2015 Nov 1;37(11):2420-38. doi: 10.1016/j.clinthera.2015.08.014. Epub 2015 Oct 1.