Morphine Sulfate Extended-release Capsules Research Articles

Factors affecting dosing regimens of morphine sulfate extended-release (KADIAN) capsules

Although most extended-release morphine formulations are indicated for use once-daily (q24h) or twice-daily (q12h), KADIAN (morphine sulfate extended-release) capsules, which contain polymer-coated, extended-release morphine sulfate pellets, are indicated for q24h and q12h dosing. This analysis identified factors that might impact decisions to choose q24h or q12h regimens for patients with chronic, nonmalignant pain. Data were obtained from a supplemental analysis of the KRONUS-MSP trial, a community-based, open-label, 4-week study in which patients with chronic, nonmalignant pain (N = 1,428) were randomized to KADIAN q24h dosed either AM or PM. At week 2, investigators could switch to q12h dosing if indicated. For this analysis, demographics, baseline pain features, efficacy outcomes (changes in pain intensity, sleep interference, quality of life [SF-36v2 Health Survey], and Patient and Clinician Global Assessments of Therapy) were compared between patients who remained on q24h regimens and those who switched to q12h. By week 4 (n = 1,042), 56.8 percent of patients reporting were on q24h dosing, and 43.2 percent were dosing q12h. Older patients remained on q24h regimens more frequently than did younger patients. There were no differences in dosing regimen based on sex or race. Mean daily KADIAN doses and baseline pain scores were lower in patients who remained on q24h compared with those who switched to q12h. Patients who switched to q12h had higher pain scores at baseline and week 2 compared with patients who remained on q24h dosing. They demonstrated a smaller degree of change on the other efficacy outcomes than those who remained on q24h dosing at the week 2 visit. However, once switched to q12h, improvements in efficacy measures at week 4 were comparable between the two schedules; Patient and Clinician Global Assessments of Therapy scores also increased compared with previous therapy. Results were significant versus baseline for all outcomes. Adverse event rates were similar for the two groups; the most common adverse events were constipation and nausea. Results demonstrate that KADIAN was effective in relieving pain and improving sleep and quality-of-life scores, regardless of whether patients dosed q24h or q12h, and that dosing decisions can be made, based on individual factors, within the first few weeks of therapy.

Assessment, stratification, and monitoring of the risk for prescription opioid misuse and abuse in the primary care setting

To evaluate potential for and incidence of aberrant drug-related behaviors among patients with chronic, moderate-to-severe pain in a primary care setting and to determine investigator compliance with universal precautions (UP) approach to pain management. Open label, multicenter. Primary care centers (N = 281) across the United States. Opioid naïve and opioid experienced with chronic, moderate-to-severe pain (N = 1,487). Morphine sulfate extended-release capsules for < or = 4 months. Tools comprising UP approach were treatment agreement, card for obtaining/tracking prescriptions, Screener and Opioid Assessment for Patients with Pain-Revised questionnaire, pill counts, pain-patient follow-up tool, investigator assessment/plan, and urine drug screens (UDSs). Proportion of patients at low, moderate, and high risk of opioid misuse/abuse based on prespecified criteria and investigator judgment, proportion of patients with aberrant drug-related behaviors, and proportion of investigators compliant with UP approach. Patients were primarily white (87 percent), women (57 percent); mean age, 53 years (range, 21-92years). At baseline, 47 percent were considered low risk for opioid misuse/abuse, 52 percent moderate, and 1 percent high. UDSs were positive for illicit/nonprescribed drugs in a proportion of patients throughout the study. Overall, 64 percent of investigators were compliant with major components of UP approach in > or = 75 percent of their patients. However, there was a tendency for investigators to assign risk levels for opioid misuse/abuse as lower than protocol specified. Most patients in these primary care study centers were categorized as at least moderate risk for opioid misuse/abuse at baseline. Most primary care investigators complied with the UP approach to pain management and risk assessment. The completion of the brief training and clinical use of the tools during the study led to retained behavior change, but there was a tendency for investigators to assign lower risk levels than those that were protocol-specified, suggesting a need for better understanding of factors influencing investigator decisions.

Effectiveness and safety of morphine sulfate extended-release capsules in patients with chronic, moderate-to-severe pain in a primary care setting

BackgroundThe purpose of this study was to determine the effectiveness and safety of morphine sulfate extended-release capsules among primary care patients with chronic, moderate-to-severe pain using a universal precautions approach that assessed and monitored risk for opioid misuse and abuse.MethodsThis open-label, uncontrolled, multicenter, prospective study was conducted in primary care centers (n = 281) and included opioid-naïve and opioid-experienced patients with either a pain score ≥4 (0 = no pain, 10 = pain as bad as you can imagine), or with unacceptable side effects while taking opioids. The patients were treated with morphine sulfate extendedrelease capsules for up to four months. Patient-rated pain intensity (worst, least, average) over the past 24 hours (0–10 scale), pain interference with seven activities of daily living (0 = no interference, 10 = completely interferes), and adverse events were recorded.ResultsOf 1487 patients who filled at least one prescription, 561 (38%) completed the study. Patients were primarily white (87%) and female (57%); 92% had pain for more than one year; and 79% were opioid-experienced. Median age was 52 years. Decreases in mean (± standard deviation) average pain scores (baseline 6.2 ± 2.3) were −0.8 ± 2.2 at visit 2 (5–14 days later), and −1.6 ± 2.3 and −1.7 ± 2.2 at visits 3 and 4 (spaced 3–4 weeks apart), respectively, and −1.1 ± 2.4 at visit 5 (included patients withdrawn from the study who were no longer taking the study drug). A similar trend was observed for worst pain and least pain scores and for pain interference with activities. Fifty-one percent of the safety population patients and 81% in the completer population reported being satisfied or very satisfied with the study treatment. Most common adverse events were typical of opioids, ie, constipation (14%), nausea (11%), vomiting (5%), and somnolence (5%).ConclusionThe results suggest that pain outcomes improved in patients with chronic, moderate-to-severe pain receiving morphine sulfate extended-release capsules within the context of a structured universal precautions approach in the primary care setting.

The Relative Bioavailability of Morphine Sulfate and Naltrexone Hydrochloride Extended Release Capsules (EMBEDA®) and an Extended Release Morphine Sulfate Capsule Formulation (KADIAN®) in Healthy Adults Under Fasting Conditions

Morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA®, King Pharmaceuticals®, Inc., Bristol, TN), indicated for the management of chronic, moderate to severe pain, contain extended release morphine pellets with a sequestered naltrexone core (MS-sNT). If the product is tampered with by crushing, naltrexone, a μ-opioid antagonist, is intended for release to mitigate morphine-induced subjective effects. The primary end point of this randomized 2-way crossover study in healthy fasted volunteers was evaluation of morphine bioequivalence between MS-sNT (treatment A) and morphine sulfate extended release capsules (KADIAN®, treatment B). Morphine pharmacokinetics were assessed predose to 72 hours postdose of single 100-mg doses of treatment A or B. Analysis of variance of ln-transformed ratios of least squares mean of the area under the concentration time curve (AUC) from time 0 to last measurable concentration (AUC0-t) and AUC from time 0 to infinity (AUCinf) and maximum serum concentration (Cmax) for treatments A versus B were performed. Ratios and 90% confidence intervals for least squares mean for AUC0-t (102.2%; 98.6-105.9%), AUCinf (97.4%; 91.2-104.1%), and Cmax (93.8%; 82.4-106.7%) indicated bioequivalence between the 2 formulations. When subjects who vomited during the 12-hour dosing interval were excluded, the confidence interval for AUC0-t and AUCinf fell within the 80%-125% range, but the lower limit for Cmax was 76.9%.

Embeda™: morphine sulfate extended-release capsules with sequestered naltrexone, a novel opioid formulation for the treatment of chronic pain

Chronic opioids are often used in the management of chronic osteoarthritis pain. Embeda™ (Alpharma Pharmaceuticals, NJ, USA) is a novel and recently approved (in the USA) extended-release formulation of morphine. It combines morphine with a sequestered, inner core of naltrexone (an opioid antagonist) that is not significantly absorbed when the capsule is taken as directed (whole). Should the capsule be tampered with, such as crushing or chewing, the naltrexone will be released, absorbed and counter the opioid effect. It is hoped that this combination morphine product will help deter patients or addicts from inappropriate use of opioids. Short-term clinical trials of Embeda demonstrate analgesia and improved physical functioning among patients with chronic pain related to osteoarthritis. This article reviews the chemistry, clinical efficacy and possible role of Embeda for the management of chronic pain.

Managing Chronic Moderate to Severe Pain—EMBEDA® (Morphine Sulfate and Naltrexone Hydrochloride) Extended Release Capsules for Oral Use

EMBEDA® (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules for oral use, indicated for the management of chronic moderate to severe pain, contain extended-release pellets of morphine sulfate with a sequestered core of naltrexone, an opioid antagonist. When EMBEDA is taken orally as directed, it is bioequivalent with regard to rate and extent of plasma morphine absorption to KADIAN® (morphine sulfate extended-release) Capsules, a similar formulation without naltrexone. EMBEDA has been shown to be significantly superior to placebo in maintaining pain relief over 12 weeks and, in one of the longest durability studies, to reduce pain intensity for up to 12 months. Upon tampering by crushing EMBEDA, naltrexone is released to mitigate morphine-induced euphoria. Euphoria and drug-liking measures after oral administration of intact or crushed EMBEDA were similar, and were reduced compared with morphine sulfate solution; crushing EMBEDA did not yield more euphoria and desirability for abuse than the intact product. The most common adverse events after long-term use were constipation, nausea, and vomiting, which are typical of opioids. Over long-term use as directed, there was no evidence of naltrexone accumulation or opioid withdrawal. The impact of formulations such as EMBEDA on the abuse rate among real-world abusers requires long-term epidemiologic studies.

Morphine sulfate extended-release capsules for the treatment of chronic, moderate-to-severe pain

Background: Morphine sulfate extended-release capsules (KADIAN®) contain polymer-coated morphine sulfate pellets that are formulated to deliver sustained plasma morphine levels with minimal fluctuation. Morphine sulfate extended-release capsules, the only opioid formulation indicated in the US for both once- and twice-daily (every 12 and every 24 h) dosing, is approved in eight dosage strengths and is effective against pain from diverse sources in a variety of patient types. The formulation of morphine sulfate extended-release capsules allows flexible dosing options: capsules can be taken whole or the contents can be sprinkled on apple sauce or delivered via a gastrostomy tube. Morphine sulfate extended-release capsules have no immediate-release component and no components that would limit high doses. Results/conclusion: The bioavailability of morphine sulfate extended-release capsules is not compromised when taken with food and dose dumping (immediate elevations in dose) does not occur when morphine sulfate extended-release capsules are taken concomitantly with alcohol. Nearly all patients taking morphine sulfate extended-release capsules for pain relief adhere to the recommended dosing frequency. The flexibility available with morphine sulfate extended-release capsules may offer clinical advantages for pain management.

KADIAN® (morphine sulfate extended-release) Capsules for treatment of chronic, moderate-to-severe, nonmalignant pain

Chronic pain, one of the most common reasons for which patients seek medical attention, is defined as pain that persists beyond the normal healing time, usually about 3 months. Chronic pain can be malignant or nonmalignant in origin, or can appear in the absence of identifiable pathology. Pharmacological treatment options include non-opioid and opioid analgesics, as well as adjuvant medications. Opioids, the most potent analgesics, are typically reserved for the treatment of chronic, moderate-to-severe pain that has not responded to non-opioid therapy. Morphine remains the gold standard among commonly used opioids. Long-acting opioids are formulated to offer continuous delivery of analgesia around the clock. These agents are formulated to maintain therapeutic blood levels of morphine, with minimal fluctuations. KADIAN Capsules, which contain polymer-coated extended-release morphine sulfate pellets, is one such formulation available for the treatment of moderate-to-severe pain for which an analgesic is indicated for more than a few days. This article reviews KADIAN and identifies unique features from early pharmacokinetic and pharmacodynamic studies, recent data on pharmacokinetic interactions with alcohol and results from recent trials in treating nonmalignant pain.

Effect of Concomitant Ingestion of Alcohol on the In Vivo Pharmacokinetics of KADIAN (Morphine Sulfate Extended-Release) Capsules

The recent withdrawal of hydromorphone hydrochloride extended-release capsules (Palladone; Purdue Pharma L.P., Stamford, CT) from the market after pharmacokinetic data revealed a risk of alcohol-induced dose-dumping prompted a re-examination of the risk-benefit profiles of extended-release drugs. Although warnings on concomitant alcohol use are included on opioid product labels, further investigations of extended-release formulations to determine the risk of dose-dumping were recommended by the US Food and Drug Administration. The present study was undertaken to assess the single-dose relative bioavailability of polymer-coated, extended-release morphine sulfate capsules (KADIAN, 100 mg; Alpharma Pharmaceuticals LLC, Piscataway, NJ). This open-label, randomized, 3-way crossover study with an additional index arm, conducted among 32 healthy male volunteers, found no significant evidence of a formulation interaction between KADIAN and alcohol, in vivo. The pharmacokinetics of serum morphine did not differ significantly among subjects taking KADIAN with water (fasted) or with 240 mL 40% alcohol under fasted or fed conditions. Analysis of variance ratios of least-squares means for ln-transformed AUC(infinity) and C(max) satisfied the criteria (90% confidence intervals within 80%-125%) to declare no drug formulation interaction among the KADIAN regimens dosed with alcohol compared with KADIAN taken with water. There were no serious adverse events or deaths reported during the study. Because of the high rate of alcohol use in the United States, the potential for drug-alcohol interactions is an important clinical concern. Although it is recommended that alcohol not be used while the patient is taking opioids, results of this in vivo study indicate that the risk of alcohol-induced dose-dumping in connection with the use of KADIAN is negligible.

(765): Long-term improvement in physical function observed in the ACTION Trial: A randomized, multi-center study of once daily AVINZA® (morphine sulfate extended-release capsules) versus twice daily OxyContin® (oxycodone hydrochloride controlled-release) for modera

The ACTION trial compared once daily AVINZA to twice daily OxyContin in subjects 30-70 years old with chronic moderate to severe low back pain. After opioid dose titration, subjects entered an 8-week evaluation phase followed by an optional 4-month extension phase. In addition to assessment of pain scores, sleep, opioid dose, and ibuprofen use for breakthrough pain, subjects completed the SF-12® quality of life questionnaire and the Work Limitations Questionnaire® (WLQ), at baseline, at the end of the dose-titration, and then monthly x6 months.

(758): In vivo pharmacokinetics of KADIAN® (morphine sulfate extended-release) capsules taken with alcohol

(758): In vivo pharmacokinetics of KADIAN® (morphine sulfate extended-release) capsules taken with alcohol

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

This multicenter trial compared the efficacy, safety, and effect on quality of life and work limitation of once-daily extended-release morphine sulfate capsules (AVINZA, A-MQD) and twice-daily controlled-release oxycodone HCI tablets (OxyContin, 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 optionalf our-month extension phase (n=174 in extension phase). Subjects were assessed using the 12-item Short-Form Health Survey (SF-12) and the Work Limitations Questionnaire (WLQ). In both groups, significant improvements were observed in the SF-12 mean scores forp hysicalf unctioning (p < 0.001), role physical (p < 0.0001), bodilyp ain (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), andp hysical summary (p = 0.0022). In both groups, SF-12 mean scores improved significantly for mental health (p < 0.01), role emotional (p < 0.01), socialfunctioning (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 O-ER group (8.5 percent versus 19.4 percent, respectively; p = 0.0149). In conclusion, compared to twice-daily OxyContin, once-daily A VINZA resulted in significantly better and earlier improvement ofp hysicalf unction and ability to work.

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

The ACTION trial, an open-label, randomized, multicenter, two-part study, compared the efficacy and safety of two sustained-release opioids (SROs), A VINZA (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. Three hundred and ninety-two subjects were enrolled in the study; 220 completed the evaluation phase, and 174 entered the extensionphase. During the latterphase, 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. 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, A VINZA 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.

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

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.

(813): Oral once-a-day AVINZA (morphine sulfate extended-release capsules) vs. twice daily OxyContin (oxycodone hydrochloride controlled-release): A randomized, multicenter study for the treatment of chronic moderate to severe low back pain

We evaluated and compared two oral SROs (once-a-day AVINZA® and twice-a-day OxyContin®) in patients with chronic moderate-to-severe low back pain. This was an open-label, randomized, parallel-group multicenter study open to enrollment of SRO-naive subjects, age 30-70, with chronic (≥ 6 months) moderate-to-severe (pain score ’4 on a 0-10 BPI scale) low back pain. A total of 392 subjects were enrolled and underwent opioid dose titration for a period of 3 to 6 weeks. Opioid dose stabilization (pain score< 4 for 3 consecutive days with≤ 2 doses of ibuprofen pain rescue medication per day) was achieved in 266 subjects (132 randomized to AVINZA and 134 to OxyContin) who then entered the 8-week evaluation phase of the study. AVINZA achieved pain control that was significantly better than OxyContin, as demonstrated by a greater decrease from baseline in pain scores evaluated 6, 9, and 12 hours after the morning dose of both opioids (p≤0.02). Subjective sleep parameters assessed by the PSQI were significantly better in the AVINZA group for the entire Evaluation period from Week 1 to 8 (p<0.04). The number of ibuprofen pain rescue medication doses adjusted for the number of patient-days was significantly lower in the AVINZA group (p<0.01). Pain control was achieved with a significantly lower daily opioid dose expressed in morphine-equivalents in the AVINZA group (median of 58 mg and 85 mg, respectively p=0.017). The incidence and severity of elicited opioid side effects was similar in the two treatment groups. This randomized trial showed that AVINZA was significantly better than OxyContin for around-the-clock pain relief and improved sleep, with the added advantage of once-a-day dosing, a lower median morphine-equivalent daily dose, fewer ibuprofen doses for breakthrough pain, and a comparable safety profile. Supported by Ligand Pharmaceuticals Inc, and Organon Pharmaceuticals USA Inc.

(827): Oral once-a-day AVINZA (morphine sulfate extended-release capsules) vs. twice daily OxyContin (oxycodone hydrochloride controlled-release) for the treatment of chronic moderate-to-severe low back pain; final (part I and part II) study results

This open-label, randomized, parallel-group multicenter study evaluated the efficacy and safety of two oral SROs (once-a-day AVINZA® and twice-a-day OxyContin®) in SRO-naive subjects, age 30-70, with chronic (≥ 6 months) moderate-to-severe low back pain. During Part I of the study 392 subjects enrolled and underwent opioid dose titration (3 to 6 weeks). Opioid dose stabilization (pain score ≤4 for 3 consecutive days with ≤2 doses per day of ibuprofen for breakthrough pain) was achieved in 266 subjects (132 randomized to AVINZA and 134 to OxyContin) who then entered an 8-week evaluation period. Following completion of Part I of the study, 174 subjects (95 AVINZA and 79 OxyContin) entered a 4-month extension phase (Part II). During Part I, AVINZA achieved significantly better pain scores (p≤ 0.02) and sleep parameters (p< 0.04) than OxyContin. These improvements were achieved with a significantly lower total daily opioid dose expressed in morphine-equivalents (median of 58mg for AVINZA and 85mg for OxyContin, p=0.017). Ibuprofen doses adjusted for the number of patient-days were significantly lower in the AVINZA group (p<0.01). These clinical benefits were maintained or further improved during Part II. At the end of Part I, the mean NRS pain scores were 3.5 for AVINZA and 3.8 for OxyContin, and further decreased to 3.1 and 3.5, respectively, at Month 4, the end of Part II (p= 0.01 favoring AVINZA). Improvements in the quality of sleep were also maintained. These results were achieved with a significantly lower daily opioid dose in the AVINZA group (86mg) compared to OxyContin (119mg morphine-equivalents) with p =0.0029. The incidence and severity of elicited opioid side effects was similar in the two treatment groups during both study phases. Final results for both parts will be presented. Supported by Ligand Pharmaceuticals Inc. and Organon Pharmaceuticals USA Inc. This open-label, randomized, parallel-group multicenter study evaluated the efficacy and safety of two oral SROs (once-a-day AVINZA® and twice-a-day OxyContin®) in SRO-naive subjects, age 30-70, with chronic (≥ 6 months) moderate-to-severe low back pain. During Part I of the study 392 subjects enrolled and underwent opioid dose titration (3 to 6 weeks). Opioid dose stabilization (pain score ≤4 for 3 consecutive days with ≤2 doses per day of ibuprofen for breakthrough pain) was achieved in 266 subjects (132 randomized to AVINZA and 134 to OxyContin) who then entered an 8-week evaluation period. Following completion of Part I of the study, 174 subjects (95 AVINZA and 79 OxyContin) entered a 4-month extension phase (Part II). During Part I, AVINZA achieved significantly better pain scores (p≤ 0.02) and sleep parameters (p< 0.04) than OxyContin. These improvements were achieved with a significantly lower total daily opioid dose expressed in morphine-equivalents (median of 58mg for AVINZA and 85mg for OxyContin, p=0.017). Ibuprofen doses adjusted for the number of patient-days were significantly lower in the AVINZA group (p<0.01). These clinical benefits were maintained or further improved during Part II. At the end of Part I, the mean NRS pain scores were 3.5 for AVINZA and 3.8 for OxyContin, and further decreased to 3.1 and 3.5, respectively, at Month 4, the end of Part II (p= 0.01 favoring AVINZA). Improvements in the quality of sleep were also maintained. These results were achieved with a significantly lower daily opioid dose in the AVINZA group (86mg) compared to OxyContin (119mg morphine-equivalents) with p =0.0029. The incidence and severity of elicited opioid side effects was similar in the two treatment groups during both study phases. Final results for both parts will be presented. Supported by Ligand Pharmaceuticals Inc. and Organon Pharmaceuticals USA Inc.

(825): Pain control in chronic non-cancer pain patients treated with once-a-day AVINZA (morphine sulfate extended-release capsules)

AVINZA is approved for once-daily administration in patients with chronic moderate to severe pain. In this study, 491 subjects with chronic non-cancer pain (≥ 4, on a 0-10 scale) were enrolled and interviewed by phone at baseline and then monthly x3 about pain control, opioid dose, sleep, and QOL. Medication was not provided by Ligand and patients were eligible if they were currently taking another opioid but getting a sub-therapeutic response. At 3 months, 339 (69%) patients remained in the study and 149 were still taking AVINZA®. The primary indications were back pain (63%), osteoarthritis (10%), and other arthropathies (8%). The median dose of AVINZA at baseline, 30 mg, increased to 60 mg at Month 1 and remained at 60 mg through Month 3. The mean score for “average daily pain” for those remaining on AVINZA for 3 months was 7.83 at entry, decreased to a mean of 5.77 at Month 1 (p< 0.01) and remained stable through Month 3. Previous research has suggested that a reduction of 2 points is clinically significant. The mean score for “pain right now” for these patients was 5.28 at baseline, and then 5.14, 5.01, and 5.13 for Months 1 through 3, respectively. This level of pain is consistent with the level patients say they can live with and still function. Significant improvements were seen in all sleep measures, including trouble falling asleep, night awakening due to pain, morning awakening due to pain, and need for sleep medications. The Composite Sleep Score, a global measure of sleep quality, improved from a mean of 5.73 at baseline to 4.93 at Month 3 (p< 0.01). In summary, patients taking AVINZA® reported improved pain control and improved sleep over a period of 3 months while their dose remained stable. Supported by Ligand Pharmaceuticals Inc.

Randomized, multi-center study of oral once-a-day AVINZA® (morphine sulfate extended-release capsules) vs. twice daily OxyContin® (oxycodone hydrochloride controlled-release) for the treatment of chronic moderate to severe low back pain

This 8-week randomized, parallel-group, multi-center study will evaluate the efficacy of oral once daily AVINZA vs. twice daily OxyContin in patients 30–70 years old requiring opioid therapy for chronic moderate to severe low back pain. Inclusion criteria include a diagnosis of chronic pain; prior sub-optimal analgesic response to treatment with other medications including NSAIDS, acetaminophen and/or prior intermittent immediate release opioid analgesics; currently not taking sustained release opioids (SROs) for pain; and demonstration of a baseline pain intensity score of >4 on an 11 point numerical scale (0= no pain; 10= pain as bad as you can imagine).

Efficacy and safety of long-term, once-daily morphine sulfate extended-release capsules in cancer patients with chronic, moderate-to-severe pain

8075 Background: This subset analysis evaluated the long-term efficacy and safety of once-daily morphine sulfate extended-release capsules (Avinza®, Ligand Pharmaceuticals [LMSER]) in cancer patients (pts) with chronic moderate-to-severe pain. Once-daily LMSER provides sustained morphine plasma levels with minimal peak-to-trough fluctuation over a 24-hr dosing interval. Methods: Pts completing a prior study with LMSER were eligible for a 1-year, multicenter, open-label trial, of which this subset analysis includes all pts with malignancies. Analgesic efficacy was assessed monthly using the Brief Pain Inventory (BPI, scale of 0 to 10); daily LMSER dose; number (#) of doses of rescue drugs; and the SF36 Survey. Safety was assessed by recording treatment-emergent side effects (TESE) and changes in lab values or physical exam. Results: The LMSER open-label study enrolled 284 pts, of which 31 (15 male; median age 61 years, range 42–78) were in this cancer pt subset; 13 completed >6 months of the trial. The median once-daily LMSER dose was 120 mg at baseline (range 60–390 mg) and 90 mg at endpoint (range 60–180 mg). During the one-year course of pain therapy, pts experienced median BPI scores for 24-hr average pain of moderate to low intensity. Pts who completed > 6 mo of the trial had a median # of rescue doses per day ranging from 1 to 2. Twenty-nine percent of pts required no rescue drugs during the trial. The once-daily LMSER dose did not correlate with the # of rescue doses required (Spearman's correlation = .36). As assessed by the SF36, changes in social function were minimal. The most common TESE were mild to moderate asthenia (35.5%) and nausea (29%). There were 11 deaths from underlying malignancy. Conclusion: Once-daily LMSER provided effective pain control despite disease progression through this 1-year study; BPI remained stable, as did the # of rescue doses required. TESE were of acceptable severity. Breakthrough pain in pts receiving higher LMSER doses was no more difficult to manage than that of pts who were on lower doses of LMSER, as reflected in the same requirement for numbers of rescue medication doses. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Pharmaceuticals Ligand Pharmaceuticals Ligand Pharmaceuticals

Efficacy and safety of long-term, once-daily morphine sulfate extended-release capsules in cancer patients with chronic, moderate-to-severe pain

8075 Background: This subset analysis evaluated the long-term efficacy and safety of once-daily morphine sulfate extended-release capsules (Avinza®, Ligand Pharmaceuticals [LMSER]) in cancer patients (pts) with chronic moderate-to-severe pain. Once-daily LMSER provides sustained morphine plasma levels with minimal peak-to-trough fluctuation over a 24-hr dosing interval. Methods: Pts completing a prior study with LMSER were eligible for a 1-year, multicenter, open-label trial, of which this subset analysis includes all pts with malignancies. Analgesic efficacy was assessed monthly using the Brief Pain Inventory (BPI, scale of 0 to 10); daily LMSER dose; number (#) of doses of rescue drugs; and the SF36 Survey. Safety was assessed by recording treatment-emergent side effects (TESE) and changes in lab values or physical exam. Results: The LMSER open-label study enrolled 284 pts, of which 31 (15 male; median age 61 years, range 42–78) were in this cancer pt subset; 13 completed >6 months of the trial. The med...