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.

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

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.

Extended-release tramadol (tramadol ER) in the treatment of chronic low back pain

2018 ◽  
Vol 4 (2) ◽  
pp. 87 ◽  
Author(s):  
Gary J. Vorsanger, PhD, MD ◽  
Jim Xiang, PhD ◽  
Theophilus J. Gana, MD, PhD ◽  
Maria Luz G. Pascual, MD, MPH ◽  
R. Rosanna B. Fleming, MS
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Pain Relief ◽  
Adverse Events ◽  
Pain Intensity ◽  
Chronic Low Back Pain ◽  
Low Back ◽  
Open Label ◽  
Once Daily ◽  
To Receive

Background: This study evaluated the safety and efficacy of tramadol ER 300 mg and 200 mg versus placebo once daily in the treatment of chronic low back pain, using an open-label run-in followed by, without washout, a randomized controlled study design.Methods: Adults with scores ≥40 on a pain intensity visual analog scale (VAS; 0 = no pain; 100 = extreme pain) received open-label tramadol ER, initiated at 100 mg once daily and titrated to 300 mg once daily during a three-week open-label run-in. Patients completing run-in were randomized to receive tramadol ER 300 mg, 200 mg, or placebo once daily for 12 weeks.Results: Of 619 patients enrolled, 233 (38 percent) withdrew from the run-in, primarily because of adverse event (n = 128) or lack of efficacy (n = 41). A total of 386 patients were then randomized to receive either 300 mg (n = 128), 200 mg (n = 129), or placebo (n = 129). Following randomization, mean scores for pain intensity VAS since the previous visit, averaged over the 12-week study period, increased more in the placebo group (12.2 mm) than in the tramadol ER 300-mg (5.2 mm, p = 0.009) and 200-mg (7.8 mm, p = 0.052) groups. Secondary efficacy scores for current pain intensity VAS, patient global assessment, Roland Disability Index, and overall sleep quality improved significantly (p ≤ 0.029 each) in the tramadol ER groups compared with placebo. The most common adverse events during the double-blind period were nausea, constipation, headache, dizziness, insomnia, and diarrhea.Conclusions: In patients who tolerated and obtained pain relief from tramadol ER, continuation of tramadol ER treatment for 12 weeks maintained pain relief more effectively than placebo. Adverse events were similar to those previously reported for tramadol ER.

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.

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