Controlled-release oxycodone and naloxone in the treatment of chronic low back pain: a placebo-controlled, randomized study.

BACKGROUND: For Canadian regulatory purposes, an analgesic study was required to complement previously completed, pivotal studies on bowel effects and analgesia associated with controlled-release (CR) oxycodone/CR naloxone. OBJECTIVES: To compare the analgesic efficacy and safety of CR oxycodone/CR naloxone versus placebo in patients with chronic low back pain. METHODS: Patients requiring opioid therapy underwent a two- to seven-day opioid washout before being randomly assigned to receive either 10 mg/5 mg CR oxycodone/CR naloxone or placebo every 12 h, titrated weekly according to efficacy and tolerability to 20 mg/10 mg, 30 mg/15 mg or 40 mg/20 mg every 12 h. After four weeks, patients crossed over to the alternative treatment for an additional four weeks. Acetaminophen/codeine (300 mg/30 mg every 4 h to 6 h as needed) was provided as rescue medication. RESULTS: Of the 83 randomized patients, 54 (65%) comprised the per-protocol population. According to per-protocol analysis, CR oxycodone/CR naloxone resulted in significantly lower mean (± SD)pain scores measured on a visual analogue scale (48.6 ± 23.1 mm versus 55.9 ± 25.4 mm; P=0.0296) and five-point ordinal pain intensity scores (2.1 ± 0.8 versus 2.4 ± 0.9; P=0.0415) compared with placebo. After the double-blinded phase, patients and investigators both preferred CR oxycodone/CR naloxone over placebo. These outcomes continued in the 79% of patients who chose to continue receiving CR oxycodone/CR naloxone in a six-month, open-label evaluation. CONCLUSIONS: In patients complying with treatment as per protocol, CR oxycodone/CR naloxone was effective for the management of chronic low back pain of moderate or severe intensity.

A randomized, double-blind, crossover comparison of the efficacy and safety of oral controlled-release tramadol and placebo in patients with painful osteoarthritis.

OBJECTIVE: To compare the efficacy and safety of controlled-release (CR) tramadol (Zytram XL, Purdue Pharma, Canada) and placebo in patients with painful osteoarthritis. METHODS: Patients underwent analgesic washout for two to seven days before random assignment to 150 mg daily of CR tramadol or placebo, and were titrated weekly to 200 mg, 300 mg or a maximum of 400 mg once daily. After four weeks, patients crossed over to the alternate treatment for another four weeks. Plain acetaminophen was provided as a rescue analgesic. All patients who completed the crossover study were eligible to receive open label CR tramadol for six months. RESULTS: Seventy-seven of 100 randomly assigned patients were evaluable for efficacy. CR tramadol resulted in significantly lower visual analogue scale pain intensity scores (37.4+/-23.9 versus 45.1+/-24.3, P=0.0009). Western Ontario and McMaster Universities osteoarthritis index subscale scores for pain (189.0+/-105.0 versus 230.0+/-115.4; P=0.0001) and physical function (632.4+/-361.3 versus 727.4+/-383.4; P=0.0205) were significantly better with CR tramadol. Total pain and disability (22.8+/-14.5 versus 27.2+/-14.8; P=0.0004), and overall pain and sleep (104.7+/-98.0 versus 141.0+/-108.2; P=0.0005) scores in the Pain and Sleep Questionnaire were significantly lower for CR tramadol. Short-form 36 Health Survey scores were significantly better during CR tramadol treatment for the pain index (38.8+/-10.8 versus 35.6+/-9.0; P=0.0100), general health perception (46.5+/-11.2 versus 44.4+/-11.6; P=0.0262), vitality (43.1+/-13.2 versus 40.2+/-13.7; P=0.0255) and overall physical components (40.8+/-8.9 versus 37.8+/-7.7; P=0.0002). CR tramadol treatment was preferred by 55.8% of patients (P=0.0005) versus 20.8% and 23.4% of patients who chose placebo or had no preference, respectively. These improvements were sustained for up to six months, and 86.5% of patients reported at least moderate benefit from CR tramadol during long-term treatment. CONCLUSION: CR tramadol is effective for the management of painful osteoarthritis.

Maintenance treatment of gastroesophageal reflux disease: an evaluation of continuous and on-demand therapy with rabeprazole 20 mg.

OBJECTIVE: To evaluate continuous therapy (COT) and on-demand therapy (ODT) with rabeprazole 20 mg for maintenance in uninvestigated gastroesophageal reflux disease (GERD). METHODS: This randomized, open-label study enrolled 331 GERD (heartburn-predominant) patients with a pre-existing proton pump inhibitor history of one month or longer, to an acute four-week trial with 20 mg rabeprazole daily for heartburn management. Patients who achieved satisfactory heartburn control during the acute phase (three days or less of heartburn, with no more than one episode rated as moderate, and heartburn rated satisfactorily or completely controlled with minimal rescue antacid use in the seven days preceding randomization) were randomly assigned to six months of rabeprazole 20 mg given as either daily COT or daily ODT, which was initiated upon symptom recurrence and stopped upon symptom resolution. Rescue antacid usage was permitted and tracked. Primary efficacy was measured as the proportion of heartburn-free days over six months. RESULTS: For the 268 patients, the mean percentage of heartburn-free days for the COT group and for the ODT group were 90.3%+/-14.8% and 64.8%+/-22.3%, respectively (P<0.0001). COT was associated with an increased number of medication intake days (154+/-40.2) versus ODT (68+/-46.1), with less heartburn episodes observed with COT versus ODT, respectively (n=7, n=26, P<0.0001). Ninety-two per cent of COT patients and 79% of ODT patients were either 'satisfied' or 'very satisfied' with treatment. The mean usage of antacids was low and similar in both groups. COT and ODT regimens were safe and well-tolerated, with a similar incidence of adverse events. CONCLUSION: Results based on symptom assessments favour COT with rabeprazole 20 mg for maintenance therapy in patients with uninvestigated GERD; however, both therapy types are safe and acceptable treatment options for selected patients.