This was a randomized, open-label, comparative, parallel group study designed to demonstrate the noninferiority of once-daily OROS<sup>®</sup> hydromorphone compared with twice-daily sustained-release (SR) oxycodone in subjects with chronic noncancer pain severe enough to require continuous opioid therapy. The core phase (24 weeks) consisted of titration and maintenance periods. This was followed by an optional extension phase (28 weeks), which collected data used to assess long-term safety and efficacy outcomes. Five hundred four subjects were randomized between the 2 treatment groups. The primary efficacy analysis showed that OROS hydromorphone was noninferior to SR oxycodone (<i>P</i> = 0.011) as measured by change in Brief Pain Inventory (BPI) pain severity subscore “pain right now.” The treatment difference with respect to change in BPI pain severity subscore “pain right now” was 0.29 (95% confidence interval: −0.27 to 0.84). The equianalgesic doses were 16 mg OROS hydromorphone and 40 mg SR oxycodone (median values). Secondary outcomes included other BPI scale items, the Medical Outcomes Study (MOS) Sleep Indices, and quality of life measured by the Short Form 36 (SF-36) questionnaire. Both treatment groups showed improvements in the main secondary efficacy endpoints. No statistically significant differences were shown between the treatment groups, except for the scores for somnolence (MOS sleep subscale) and physical functioning (SF-36), which both had a statistically significant difference between treatments groups in favor of OROS hydromorphone. Both study medications had equivalent and acceptable safety profiles. The results of this open-label study showed that once-daily OROS hydromorphone is a safe and well-tolerated treatment for chronic pain and as efficacious as twice-daily SR oxycodone. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
<b>OBJECTIVE: </b>Tapentadol is a novel, centrally acting analgesic with two mechanisms of action, mu-opioid receptor agonism and norepinephrine reuptake inhibition, in a single molecule. This phase III, randomized, double-blind, active-controlled study evaluated the tolerability of tapentadol immediate release (IR) and oxycodone IR for low back pain or osteoarthritis pain (hip or knee), using flexible dosing over 90 days.<b>METHODS: </b>Patients (N = 878) were randomly assigned (4:1 ratio) to receive tapentadol IR (50 or 100 mg, q4-6h, p.o.) or oxycodone IR (10 or 15 mg, q4-6h, p.o.). Tapentadol IR was evaluated for tolerability over 90 days, tolerability relative to oxycodone IR, withdrawal symptoms, and pain intensity. This study was not placebo-controlled, which limited efficacy evaluations.<b>RESULTS: </b>In total, 849 intent-to-treat patients received tapentadol IR (n = 679) or oxycodone IR (n = 170), and among these, 391 patients (57.6%) in the tapentadol IR group and 86 patients (50.6%) in the oxycodone IR group completed the study. Gastrointestinal events, including nausea (18.4% vs 29.4%), vomiting (16.9% vs 30.0%), and constipation (12.8% vs 27.1%), were reported by 44.2% of patients receiving tapentadol IR and 63.5% of patients receiving oxycodone IR, respectively. Nervous system events, including dizziness (18.1% vs 17.1%), headache (11.5% vs 10.0%), and somnolence (10.2% vs 9.4%), were reported by 36.7% of patients receiving tapentadol and 37.1% of patients receiving oxycodone, respectively. Odds ratios (tapentadol:oxycodone) showed that the incidences of somnolence and dizziness were similar; however, nausea, vomiting, and constipation were significantly less likely with tapentadol IR compared with oxycodone IR. The pattern of withdrawal symptoms suggests that drug tapering may not be necessary after tapentadol IR treatment of this duration. Pain intensity measurements showed similar efficacy for tapentadol and oxycodone.<b>CONCLUSION: </b>During this 90-day study, tapentadol IR was associated with improved gastrointestinal tolerability compared with oxycodone IR while providing similar pain relief. Trial registration information: NCT00364546.
OBJECTIVE: This study compared the efficacy and tolerability of a once-daily controlled-release formulation of hydromorphone and twice-daily extended-release (ER) oxycodone in patients with chronic, moderate to severe osteoarthritis (OA) pain. METHODS: The study consisted of a 14-day dose-titration and stabilization phase and a 28-day maintenance phase. OROS hydromorphone and ER oxycodone were initiated at dosages of 8 mg QD and 10 mg BID, respectively. Patients maintained diaries in which they rated their pain (from 0 = none to 3 = severe) and pain relief (from 0 = no relief to 4 = complete relief). Noninferiority analyses were conducted on all primary and secondary efficacy variables. RESULTS: One hundred thirty-eight patients (71 OROS hydromorphone, 67 ER oxycodone) received treatment (safety population), and 83 (60.1%) completed the study. There were no statistically significant differences between groups in total WOMAC scores at end point, and similar improvements from baseline in the WOMAC physical function, stiffness, and pain scales were observed in both groups. CONCLUSIONS: Once-daily OROS hydromorphone and twice-daily ER oxycodone provided similar pain relief in these patients with OA of the knee or hip. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
This large, open-label, randomized, parallel-group, multicenter study compared two oral sustained-release opioids (SROs)--AVINZA (A-MQD), morphine sulfate extended-release capsules given once a day, and OxyContin (O-ER), oxycodone modified-release tablets given twice a day--in SRO-naive subjects ages 30 to 70 with chronic, moderate to severe low back pain. Of the 392 subjects enrolled and randomized, 266 (132 in the A-MQD group and 134 in the O-ER group) completed the opioid dose titration phase and entered an eight-week evaluation phase. During the evaluation phase, A-MQD achieved significantly better pain control than O-ER, as demonstrated by a greater decrease from baseline in pain scores obtained four times daily during weeks one, four, and eight (p = 0.002). The number of breakthrough-pain rescue medication doses adjusted for the number of patient days was significantly lower in the A-MQD group (p < 0.0001). Better pain control with A-MQD was achieved with a significantly lower daily opioid dose than with O-ER (mean 69.9 mg and 91 mg morphine equivalents, respectively; p = 0.0125). Quality of sleep was significantly better with A-MQD for the entire evaluation phase (p = 0.0026). The incidence and severity of elicited opioid side effects were similar in the two groups. This trial demonstrated that once-daily A-MQD provides consistent around-the-clock pain relief in patients with low back pain. In patients who completed opioid dose titration, A-MQD was significantly better than O-ER for reducing pain and improving sleep, while requiring a lower daily opioid dose.
OBJECTIVE: To assess the long-term efficacy, tolerability and safety of polymer-coated extended-release morphine sulfate (P-ERMS) (KADIAN) compared with controlled-release oxycodone HCl (CRO) (OxyContin) in treating chronic, nonmalignant, moderate to severe pain in a community-based outpatient population.
DESIGN: Phase IV, prospective, randomized, open-label.
PARTICIPANTS: Adults (N = 112) with chronic, nonmalignant, moderate to severe pain with visual numeric scale (VNS) scores > or = 4 (0 = no pain; 10 = worst pain).
INTERVENTIONS: Patients were randomized to receive either P-ERMS once-daily (QD) dosing or CRO twice-daily (BID) dosing for a 24-week treatment period. Upward titration of dose and switching P-ERMS to BID or CRO to thrice-daily (TID) dosing was allowed Weeks 2-24.
MAIN OUTCOME MEASURES: Quality of life (Physical [PCS] and Mental [MCS] Component Summary scores of the SF-36v2 Health Survey), pain and sleep scores (0-10), and patient and clinician assessments of current therapy (-4 to +4).
RESULTS: Patients in both treatment groups experienced significant improvements in PCS scores (P-ERMS, +2.6; CRO, +3.1; p < 0.05 vs. baseline); patients taking CRO also demonstrated improvements in MCS scores (+4.7, p < 0.05 vs. baseline). Both groups attained significant reductions from baseline to 24 weeks in pain (P-ERMS, -2.0; CRO, -1.4; p < or = 0.001 vs. baseline); the reduction with P-ERMS was clinically meaningful (as defined by at least a 2-point reduction in VNS score). Patients attained significant improvement in sleep scores (P-ERMS, -2.6; CRO, -1.6; p < 0.001 vs. baseline; p < 0.05, P-ERMS vs. CRO). At Week 24, both groups indicated significantly increased patient (P-ERMS, +2.6; CRO, +1.7; p < 0.001 vs. baseline) and clinician (P-ERMS, +4.0; CRO, +3.1; p < 0.001 vs. baseline) global assessments of therapy. After 24 weeks, all patients on P-ERMS were dosing within the FDA-approved frequencies (65% QD, 35% BID); 56% of patients on CRO dosed BID, but 38% dosed TID and 6% dosed four times daily (QID). Most common adverse events were constipation, nausea, and somnolence, with no significant difference between treatment groups.
CONCLUSIONS: P-ERMS and CRO both relieved chronic nonmalignant pain in this community-based population; however, patients taking P-ERMS dosed in accordance with FDA-approved frequencies (QD/BID); 44% of those taking CRO dosed more frequently (TID/QID).
