A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Arm, Multicenter Study in Subjects With End-Stage Joint Disease to Compare the Frequency of Constipation Symptoms in SubjectsTreated With Tapentadol IR and Oxycodone IR Using a Bowel Function Patient Diary
A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Arm, Multicenter Study in Subjects With End-Stage Joint Disease to Compare the Frequency of Constipation Symptoms in SubjectsTreated With Tapentadol IR and Oxycodone IR Using a Bowel Function Patient Diary
The purpose of this study is to compare bowel function/constipation that occurs during tapentadol treatment with that occuring during oxycodone treatment, as measured by the frequency of spontaneous bowel movements per week. The frequency of spontaneous bowel movements will be determined from a Bowel Function Patient Diary completed by the enrolled sujbects.
Chronic pain from end-stage degenerative joint disease is often moderate to severe in intensity and results in a relatively constant level of pain requiring continuous pain relief medication. Despite available pain relief medications, 60% to 80% of subjects suffering from chronic pain are currently inadequately treated. Opioid pain medications are central to the effective treatment of moderate to severe pain. However, opioid therapy is frequently complicated by side effects. Constipation is one of the most commonly reported side effects and most debilitating. An opioid medication that provides pain relief with a reduced incidence of constipation symptoms would improve the capability of subjects to stay on medication to achieve the long-term relief they need. This is a randomized, double-blind, placebo- and active-controlled, parallel-arm, multicenter study with 4 treatment groups of subjects who have moderate to severe chronic pain from end-stage degenerative joint disease of the hip or knee and who are candidates for primary total or partial joint replacement. The study consists of 3 periods: a pretreatment period (a 14-day screening for study eligibility and a 7-day washout of any previously taken opioid medication), a double-blind treatment period (a 14-day IR treatment phase followed by a 28-day ER treatment phase), and a follow-up period (1 study-site visit within 4 days after the last dose of study drug is taken and 1 telephone contact within 10 to 14 days after the last dose of study drug is taken). On Day 1 of the IR treatment phase, patients will be randomly assigned to 1 of 4 possible treatment groups to receive 50 mg CG5503 IR, 75 mg CG5503 IR, 10 mg oxycodone IR, or placebo daily every 4 to 6 hours. At the beginning of the ER treatment phase, patients' study drugs will be transitioned to the ER form (by conversion from the IR to approximate equivalent total daily doses of the ER form) of their randomly assigned study drug of tapentadol ER, oxycodone CR, or placebo. The ER study drugs will be taken every 12 hours b.i.d. Dosages will be adjustable, with the study site personnel oversight, to ensure adequate pain relief is provided. Beginning with the washout period, patients will be given hand-held computer diaries in which to record their pain intensity, pain relief, bowel movement information, and answer questions on any nausea or vomiting that may occur. In addition, patients will write down the times and dosages of all medications they take during the study in a medication diary. Safety and tolerability will be assessed using physical examination, monitoring of adverse events, clinical and laboratory measures, and 12 lead ECG results. The first study hypothesis is that both tapentadol IR dosages are more effective than placebo in relieving pain based on the SPID score recorded by the patients over the first 5 days of the study. The second study hypothesis is that the Bowel Function Patient Diary results for both tapentadol IR dosages demonstrate improved tolerability compared to oxycodone IR 10 mg, based on the number of spontaneous bowel movements per week over the first 2 weeks of the study. In the IR treatment phase, each patient will take CG5503 IR 50 mg, CG5503 IR 75 mg, oxycodone IR 10 mg, or placebo orally every 4 to 6 hours for 14 days. In the ER treatment phase, dosages of the IR treatment groups will be converted to approximately equivalent dosages of the ER form of the assigned study drug: tapentadol ER, oxycodone CR, or placebo. Dosages may range from 100 to 500 mg/day of tapentadol ER and 20 to 60 mg/day of oxycodone CR taken orally 2x daily for 28 days.
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