The ACTION study: A randomized, open-label, multicenter trial comparing once-a-day extended-release morphine sulfate capsules (AVINZA®) to twice-a-day controlled-release oxycodone hydrochloride tablets (OxyContin®) for the treatment of chronic, moderate to severe low back pain

2006 ◽  
Vol 2 (3) ◽  
pp. 155 ◽  
Author(s):  
Richard L. Rauck, MD ◽  
Stephen A. Bookbinder, MD ◽  
Timothy R. Bunker, MD ◽  
Christopher D. Alftine, MD ◽  
Richard Ghalie, MD ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Pain Control ◽  
Extended Release ◽  
Morphine Sulfate ◽  
Dose Titration ◽  
Low Back ◽  
Open Label ◽  
Opioid Dose ◽  
Evaluation Phase

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 AMQD 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.

scholarly journals A randomized, open-label study of once-a-day AVINZA® (morphine sulfate extended-release capsules) versus twice-a-day OxyContin® (oxycodone hydrochloride controlled-release tablets) for chronic low back pain: The extension phase of the ACTION trial

2006 ◽  
Vol 2 (6) ◽  
pp. 325 ◽  
Author(s):  
Richard L. Rauck, MD ◽  
Stephen A. Bookbinder, MD ◽  
Timothy R. Bunker, MD ◽  
Christopher D. Alftine, MD ◽  
Richard Ghalie, MD ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Extended Release ◽  
Extension Phase ◽  
Low Back ◽  
Open Label ◽  
Pain Scores ◽  
Evaluation Phase ◽  
Morphine Equivalent

Study design and objective: The ACTION ® trial, an open-label, randomized, multicenter, two-part study, compared the efficacy and safety of two 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 subjects with chronic, moderate to severe low back pain. The first part of the study, the evaluation phase, was followed by an optional four-month extension phase aimed at evaluating the long-term stability of pain control, SRO dose, and quality of sleep.Results: Three hundred and ninety-two subjects were enrolled in the study; 220 completed the evaluation phase, and 174 entered the extension phase. During the latter phase, subjects in the A-MQD group (n = 79) continued to report lower pain scores, better quality of sleep, lower daily morphine-equivalent doses (means of 86 mg versus 119 mg), and a comparable usage of ibuprofen compared to subjects in the O-ER group (n = 95). The incidence and severity of elicited opioid side effects were similar between the two groups.Conclusions: Both study drugs resulted in significant pain relief and improved sleep in SRO-naive patients with chronic low back pain, and this outcome was attained with a stable daily SRO dose. In patients who completed opioid dose titration, AVINZA performed significantly better than OxyContin in reducing pain scores and improving sleep—with a lower morphine-equivalent daily dose—during both the evaluation and extension phases.

Six-month, open-label study of hydrocodone extended release formulated with abuse-deterrence technology: Safety, maintenance of analgesia, and abuse potential

2016 ◽  
Vol 12 (2) ◽  
pp. 139 ◽  
Author(s):  
Martin E. Hale, MD ◽  
Yuju Ma, MS ◽  
Richard Malamut, MD
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Pain Intensity ◽  
Chronic Low Back Pain ◽  
Extended Release ◽  
Study Drug ◽  
Dose Titration ◽  
Controlled Study ◽  
Low Back ◽  
Open Label

Objective: To evaluate long-term safety, maintenance of analgesia, and aberrant drug-related behaviors of hydrocodone extended release (ER) formulated with CIMA® Abuse-Deterrence Technology.Design: Phase 3, multicenter, open-label extension.Setting: Fifty-six US centers.Patients: Adults with chronic low back pain completing a 12-week placebo-controlled study of abuse-deterrent hydrocodone ER were eligible. One hundred eighty-two patients enrolled and received ≥1 dose of study drug, 170 entered open-label treatment, and 136 completed the study.Interventions: Patients receiving hydrocodone ER in the 12-week, placebo-controlled study continued their previous dose unless adjustment was needed; those previously receiving placebo (n = 78) underwent dose titration/adjustment to an analgesic dose (15-90 mg every 12 hours). Patients received 22 weeks of open-label treatment.Main outcome measures: Safety: adverse events (AEs). Maintenance of analgesia: worst pain intensity (WPI) and average pain intensity (API) at each study visit. Aberrant drug behavior: study drug loss and diversion. Results: AEs were reported for 65/182 (36 percent) patients during dose titration/adjustment and 88/170 (52 percent) during open-label treatment. No treatment-related serious AEs were reported. There were no clinically meaningful trends in other safety assessments, including physical examinations and pure tone audiometry. One patient receiving hydrocodone ER 30 mg twice daily experienced a severe AE of neurosensory deafness that was considered treatment related. Mean WPI and API remained steady throughout open-label treatment. Six (3 percent) patients reported medication loss, and 5 (3 percent) reported diversion.Conclusions: Abuse-deterrent hydrocodone ER was generally well tolerated in patients with chronic low back pain, maintained efficacy, and was associated with low rates of loss and diversion.

Efficacy and safety of a hydrocodone extended-release tablet formulated with abuse-deterrence technology in patients with moderate-to-severe chronic low back pain

2015 ◽  
Vol 11 (6) ◽  
pp. 507 ◽  
Author(s):  
Martin E. Hale, MD ◽  
Thomas R. Zimmerman, MD ◽  
Eli Eyal, MSc ◽  
Richard Malamut, MD
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Extended Release ◽  
Study Drug ◽  
Low Back ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Drug Loss ◽  
Efficacy Measure

Objective: To evaluate efficacy and safety of hydrocodone bitartrate extended-release (ER) tablets developed with CIMA® Abuse-Deterrence Technology (ADT) versus placebo in alleviating moderate-to-severe pain in patients with chronic low back pain.Design: Phase 3, randomized, double-blind study consisting of a screening period (7-14 days), open-label titration period (≤6 weeks), and double-blind treatment period (≤12 weeks).Setting: Seventy-eight US centers.Main outcome measures: Changes from baseline at week 12 in weekly average of daily worst pain intensity (WPI; primary efficacy measure), weekly average pain intensity (API; secondary efficacy measure), adverse events (AEs), and study drug loss and diversion.Results: Patients (N = 625) who entered open-label dose titration and identified the analgesic hydrocodone ER dose (30-90 mg every 12 h) providing optimal pain relief with minimal AEs were randomized to hydrocodone ER (n = 191) or placebo (n = 180) for double-blind treatment at the identified dose; 297 patients completed the study. Least squares means [SE] changes from baseline were significantly greater (worsening pain; 11-point scale) with placebo than hydrocodone ER in weekly average of daily WPI (0.74 [0.15] vs 0.11 [0.14]; p < 0.001) and weekly API (0.55 [0.14] vs −0.03 [0.12]; p < 0.001). The most common AEs with hydrocodone ER were constipation (14 percent) and nausea (10 percent). Study drug loss (≤4 percent) and diversion (≤2 percent) rates were low.Conclusions: Hydrocodone ER formulated with ADT was significantly more effective than placebo in alleviating chronic low back pain and demonstrated a safety profile consistent with that of opioids, with a low occurrence of study drug loss and diversion.

A randomized, open-label, multicenter trial comparing once-a-day AVINZA® (morphine sulfate extended-release capsules) versus twice-a-day OxyContin® (oxycodone hydrochloride controlled-release tablets) for the treatment of chronic, moderate to severe low back pain: Improved physical functioning in the ACTION trial

2007 ◽  
Vol 3 (1) ◽  
pp. 35 ◽  
Author(s):  
Richard L. Rauck, MD ◽  
Stephen A. Bookbinder, MD ◽  
Timothy R. Bunker, MD ◽  
Christopher D. Alftine, MD ◽  
Steven Gershon, MD ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Physical Functioning ◽  
Mental Component Summary ◽  
Extended Release ◽  
Bodily Pain ◽  
Multicenter Trial ◽  
Low Back ◽  
Once Daily ◽  
Evaluation Phase

This multicenter trial compared the efficacy, safety, and effect on quality of life and work limitation of once-daily extended-release morphine sulfate capsules (AVINZA9, A-MQD) and twice-daily controlled-release oxycodone HCl tablets (OxyContin9, O-ER) in subjects with chronic, moderate to severe low back pain. After randomization and a period of opioid dose titration, subjects (n = 266) underwent an eight-week evaluation phase and an optional four-month extension phase (n = 174 in extension phase). Subjects were assessed using the 12-item Short-Form Health Survey9 (SF-12) and the Work Limitations Questionnaire9 (WLQ). In both groups, significant improvements were observed in the SF-12 mean scores for physical functioning (p < 0.001), role physical (p < 0.0001), bodily pain (p < 0.0001), physical summary (p < 0.001), and mental component summary (p < 0.005). At the end of the titration period, greater relative improvements from baseline were seen in the SF-12 section on physical components in the A-MQD group versus the O-ER group, with significant differences observed for physical functioning (p = 0.0374), role physical (p = 0.0341), bodily pain (p = 0.0001), and physical summary (p = 0.0022). In both groups, SF-12 mean scores improved significantly for mental health (p < 0.01), role emotional (p < 0.01), social functioning (p < 0.0005), vitality (p < 0.005), and the mental component summary (p < 0.005), but no significant differences were noted between the two groups. Both groups reported improvement from baseline in WLQ physical demands scores, with no significant differences noted between the two groups. At the end of the evaluation phase, fewer subjects were unable to work due to illness or treatment in the A-MQD group than in the OER group (8.5percent versus 19.4percent, respectively; p = 0.0149). In conclusion, compared to twice-daily OxyContin, once-daily AVINZA resulted in significantly better and earlier improvement of physical function and ability to work.

scholarly journals Dose Conversion Between Tapentadol Immediate and Extended Release for Low Back Pain

2010 ◽  
Vol 1;13 (1;1) ◽  
pp. 61-70
Author(s):  
Mila S. Etropolski
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Pain Intensity ◽  
Chronic Low Back Pain ◽  
Extended Release ◽  
Immediate Release ◽  
Low Back ◽  
Open Label ◽  
Double Blind ◽  
The Mean

Background: Tapentadol, a novel, centrally acting analgesic with 2 mechanisms of action (µopioid receptor agonism and norepinephrine reuptake inhibition), has been developed in an immediate-release (IR) and an extended-release (ER) formulation. Determination of the safety and equianalgesic ratios for conversion between formulations is important for physicians with patients taking tapentadol IR who may want to switch to tapentadol ER, or vice versa, for any reason. Objectives: To test whether the total daily dose (TDD) of tapentadol IR may be directly converted into a comparable TDD of tapentadol ER, and vice versa, with equivalent efficacy and comparable safety. Study Design: Randomized, double-blind, 2-period (2 weeks each) crossover study. Setting: Study centers (N = 13) in the United States. Methods: Patients with moderate to severe chronic low back pain received tapentadol IR 50, 75, or 100 mg every 4 or 6 hours (maximum TDD, 500 mg) during the 3-week open-label period to identify an optimal, stable dose of tapentadol IR for each patient. Patients were then randomized in a 1:1 ratio to receive, during the first 2-week double-blind period, either the optimal dose of tapentadol IR identified during the open-label period or a TDD of tapentadol ER (100, 150, 200, or 250 mg bid) that was as close as possible to the TDD of tapentadol IR from the open-label period. During a subsequent, 2-week double-blind period, patients received whichever formulation was not received during the first double-blind period. The primary endpoint was the mean average daily pain intensity (on an 11-point numerical rating scale) during the last 3 days of each double-blind treatment period. If the 95% confidence intervals (CIs) of the least squares mean difference between formulations were within the range of −2 to 2, the formulations were considered equivalent. Results: Of the 88 patients who were randomized, 72 completed both double-blind treatments, and 60 were included in the per-protocol analysis. The mean (standard deviation [SD]) pain intensity score decreased from 7.3 (1.19) pre-treatment to 4.2 (2.13) after 3 weeks of open-label treatment with tapentadol IR and remained constant throughout double-blind treatment (3.9 or 4.0 each week) for both formulations. The mean (SD) of the average pain intensity scores over the last 3 days of double-blind treatment was 3.9 (2.17) with tapentadol IR and 4.0 (2.29) with tapentadol ER, for an estimated difference of 0.1 (95% CI, −0.09 to 0.28). For both tapentadol IR and tapentadol ER, the median TDD administered was 300.0 mg, and acetaminophen was used by 39.5% and 45.2% of patients, respectively. The incidence of treatment-emergent adverse events during double-blind treatment was similar between the tapentadol IR and tapentadol ER groups. Limitations: Use of rescue medication theoretically could have influenced pain measurements, but in practice, pain measurements did not differ between treatments. Conclusions: Approximately equivalent TDDs of tapentadol IR and tapentadol ER provided equivalent analgesic efficacy for the relief of moderate to severe chronic low back pain and were similarly well tolerated, allowing for direct conversion between the 2 formulations. Key words: Chronic low back pain, conversion, efficacy, equivalence, extended release, immediate release, opioid, safety, tapentadol

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