The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Lee Techner - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of clinical outcomes with Alvimopan in clinical practice a national matched cohort study in patients undergoing bowel resection
    Annals of Surgery, 2012
    Co-Authors: Conor P Delaney, Sara Poston, Melinda Maggard Gibbons, Christine J Vandepol, Suzanne F Cook, Christopher Craver, Amy W Rachfal, Michael Calloway, Lee Techner
    Abstract:

    Objective: To evaluate in-hospital clinical outcomes after open and laparoscopic bowel resection (BR) with or without Alvimopan treatment. Background: Delayed return of gastrointestinal function after BR may be associated with greater postoperative morbidity and increased hospital length of stay (LOS). In clinical trials, Alvimopan—a peripherally acting μ-opioid receptor antagonist—accelerated gastrointestinal recovery after open BR. Methods: A retrospective matched-cohort study (NCT01150760) was conducted using a national inpatient database. Each Alvimopan patient was exact matched (surgical procedure, surgeon specialty) and propensity score matched (baseline characteristics) to a nonAlvimopan BR patient. Outcomes included gastrointestinal and other morbidity (cardiovascular, pulmonary, infection, cerebrovascular, thromboembolic); mortality; readmission rate; and intensive care unit (ICU) stay (intent-to-treat [ITT] population). Postoperative LOS and estimated cost were also compared (modified ITT population). Results: Each cohort included 3525 ITT patients with similar baseline characteristics. Gastrointestinal (29.8% vs 35.7%) and other morbidity (cardiovascular [19.4% vs 24.0%], pulmonary [7.3% vs 10.5%], infectious [9.6% vs 11.8%], thromboembolic [1.2% vs 2.1%]), mortality (0.4% vs 1.0%), and mean ICU stay (0.3 vs 0.6 days) were lower in the Alvimopan group (P ≤ 0.003 for each). Postoperative LOS and estimated direct cost were lower for all Alvimopan patients and after laparoscopic and open BR (LOS: –1.1, –0.8, and –1.8 days respectively; cost: –$2345, –$1382, and –$3218, respectively; P ≤ 0.0008 for each). Conclusions: On average, Alvimopan-treated patients had a lower incidence of mortality and most incidents of morbidities. Length of stay, ICU use, and estimated cost were also lower with comparable readmissions. These results in patients outside the clinical trial setting include laparoscopic colectomy and demonstrate a potential association between acceleration of gastrointestinal recovery and improved early postoperative outcomes.

  • impact of Alvimopan entereg on hospital costs after bowel resection results from a large inpatient database
    P & T : a peer-reviewed journal for formulary management, 2011
    Co-Authors: Sara Poston, Michael S Broder, Melinda Maggard Gibbons, Robert Maclaren, Eunice Chang, Christine J Vandepol, Suzanne F Cook, Lee Techner
    Abstract:

    Purpose: Delayed gastrointestinal (GI) recovery after bowel resection is associated with longer hospital stays and increased health care costs. Alvimopan (Entereg), a peripherally acting mu-opioid receptor antagonist, accelerates GI recovery after bowel-resection surgery. We undertook a study to evaluate the economic impact of Alvimopan in clinical practice. Methods: We conducted a retrospective matched cohort study using data from a large national hospital database and identified adults who had undergone small-bowel or largebowel resection with primary anastomosis. The patients were discharged between January 1, 2009, and June 30, 2009. The surgery was performed at a hospital where Alvimopan was used at least once during the study period. We matched each Alvimopan patient (“user”) with two controls (“non-users”). The primary outcome of total hospital costs (including the cost of Alvimopan) and secondary outcomes of cost components and length of stay were compared between groups. Results: The final study cohort included 480 Alvimopan patients and 960 matched controls. The mean total hospital cost was $12,865 for Alvimopan patients, compared with $13,905 for controls, for a difference of $1,040 (P = 0.033). There was a nonsignificant trend toward lower ileus-related costs between groups ($83 for Alvimopan vs. $114 for controls, P = 0.086). Pharmacy and diagnostic radiology costs did not differ significantly. The mean length of stay was 5.6 days for Alvimopan patients and 6.5 days for controls (P < 0.001). Conclusion: Patients receiving Alvimopan capsules had significantly lower total hospital costs compared with controls. Along with other initiatives to improve quality and reduce costs of surgical care, Alvimopan might be a good choice for

  • Alvimopan for the management of postoperative ileus after bowel resection characterization of clinical benefit by pooled responder analysis
    World Journal of Surgery, 2010
    Co-Authors: Kirk A Ludwig, Bruce G Wolff, Conor P Delaney, Anthony J Senagore, Eugene R. Viscusi, Lee Techner
    Abstract:

    Background A pooled post hoc responder analysis was performed to assess the clinical benefit of Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, for the management of postoperative ileus after bowel resection.

  • Clinical Trials Registration Numbers NCT00388258,
    2010
    Co-Authors: Lee Techner, Bruce G Wolff, Conor P Delaney, Eugene R. Viscusi, Anthony Senagore, Ó Société, Internationale Chirurgie, Nct Nct Nct, Kirk Ludwig
    Abstract:

    Background A pooled post hoc responder analysis was performed to assess the clinical benefit of Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, for the management of postoperative ileus after bowel resection. Methods Adult patients who underwent laparotomy for bowel resection scheduled for opioid-based intravenous patient-controlled analgesia received oral Alvimopan or placebo preoperatively and twice daily postoperatively until hospital discharge or for 7 postoperative days. Th

  • economic analysis of Alvimopan in north american phase iii efficacy trials
    American Journal of Health-system Pharmacy, 2009
    Co-Authors: Timothy J Bell, Conor P Delaney, Michael D. Kraft, Sara Poston, Anthony J Senagore, Lee Techner
    Abstract:

    Purpose. The economic effect of the use of Alvimopan in four randomized, double-blind, placebo-controlled, Phase III, North American efficacy trials was analyzed. Methods. Patients were eligible for the study if they were 18 years or older, were undergoing laparotomy for partial small or large bowel resection with primary anastomosis, and were scheduled for postoperative pain management with opioid-based i.v. patient-controlled analgesia. Patients analyzed in the North American Phase III trials received placebo or Alvimopan 12 mg orally before surgery. Doses were administered twice daily beginning the day after surgery until hospital discharge or for a maximum of 15 doses. Results. Compared with placebo, Alvimopan was associated with a significantly shorter mean time to gastrointestinal (GI) recovery and a significantly shorter mean time to a written discharge order. Alvimopan was also associated with a mean hospital length of stay (LOS) of one full day less than placebo. The mean cost of Alvimopan based on a mean of 8.9 12-mg doses was $558.00; the Alvimopan cost at the upper limit of allowed dosing was $937.50. Combining the Alvimopan and hospital costs for each patient, total costs for the Alvimopan group were estimated to be lower than for the placebo group. Conclusion. In a post hoc analysis, Alvimopan was associated with significantly faster upper and lower GI recovery after bowel resection and a mean LOS reduction of one day compared with placebo. The mean estimated hospital cost was $879–$977 less for patients who received Alvimopan compared with placebo. The base-case and sensitivity analyses suggest that, on average, the use of Alvimopan compared with placebo may have a cost-saving effect in the hospital setting.

Bruce Wallin - One of the best experts on this subject based on the ideXlab platform.

  • Alvimopan for postoperative ileus following bowel resection a pooled analysis of phase iii studies
    Annals of Surgery, 2007
    Co-Authors: Conor P Delaney, John G Fort, Lee Techner, Bruce G Wolff, Anthony J Senagore, Eugene R. Viscusi, Bruce Wallin
    Abstract:

    In the United States, nearly 350,000 patients undergo colorectal or small bowel resection (BR) annually.1 These patients spend an average of 11 days in the hospital and account for >$15 billion in annual national healthcare costs.1 All of these patients experience postoperative ileus (POI), a temporary impairment of gastrointestinal (GI) function.2–4 Moreover, associated GI complications are common.5 For patients who undergo BR, length of hospital stay (LOS) is dictated mostly by timing of GI recovery. To facilitate GI recovery, some specialized centers have used accelerated care pathways, although readmission rates have been increased in some cases.6–10 Reducing surgical complications and further accelerating GI recovery after BR could increase patient comfort, decrease the average LOS, and reduce costs, readmission rates, and other demands on healthcare resources.11 The etiology of POI is complex, and major intrinsic contributing factors include surgical stress (ie, from physical manipulation of the bowel), secretion of inflammatory mediators and endogenous opioids in the GI tract, and changes in hormone levels and electrolyte and fluid balance.12–15 Opioids are the most widely prescribed analgesics used to treat postoperative pain.16 However, opioids bind to mu-opioid receptors within the gut, exacerbating POI.12,14 No specific treatment currently exists for the treatment or prevention of POI. Alvimopan is a novel, oral, peripherally acting, mu-opioid receptor (PAM-OR) antagonist that has been studied in patients undergoing abdominal and pelvic surgery.17–19 In 3 phase III multicenter trials, Alvimopan accelerated GI recovery after BR or total abdominal hysterectomy (TAH).17–19 Although the results favored Alvimopan across studies, statistical significance and magnitude of treatment effect were not consistent with regard to the primary endpoint, a composite assessment that included toleration of solid food and first passage of flatus or stool (GI-3). Further, the individual studies were not powered sufficiently to investigate infrequent but clinically important postoperative morbidities or investigate potential differences between the 6- and 12-mg doses. Hence, a pooled analysis was performed to examine the safety and efficacy of Alvimopan within the subgroup of patients who underwent BR.

  • a double blind randomized placebo controlled phase iii study of the safety of Alvimopan in patients who undergo simple total abdominal hysterectomy
    American Journal of Obstetrics and Gynecology, 2006
    Co-Authors: Thomas J Herzog, John G Fort, Lee Techner, Kathie Gabriel, Robert L Coleman, James P Guerrieri, Bruce Wallin
    Abstract:

    Objective The purpose of this study was to investigate the safety and efficacy of Alvimopan, a novel peripherally acting mu-opioid receptor antagonist, in patients who undergo simple total abdominal hysterectomy. Study design Women (n = 519) were randomized (4:1) to receive Alvimopan 12 mg (n = 413) or placebo (n = 106) ≥2 hours before the operation then twice daily for 7 days (hospital and home). Adverse events were monitored up to 30 days after the last dose of study drug was administered. Efficacy was assessed for 7 postoperative days. Results Overall, the most common adverse events were nausea, vomiting, and constipation; P Conclusion Alvimopan has a safety profile that is similar to that of placebo and provides significantly improved lower gastrointestinal recovery in women who undergo simple total abdominal hysterectomy.

  • Alvimopan a peripherally acting mu opioid receptor antagonist compared with placebo in postoperative ileus after major abdominal surgery results of a randomized double blind controlled study
    Surgical Endoscopy and Other Interventional Techniques, 2006
    Co-Authors: Eugene R. Viscusi, Lee Techner, Kathie Gabriel, Scott M Goldstein, Thomas A Witkowski, A Andonakakis, R Jan, Bruce Wallin
    Abstract:

    Background Alvimopan is a peripherally acting mu-opioid receptor (PAM-OR) antagonist for accelerating gastrointestinal recovery after surgery.

  • effect of Alvimopan and codeine on gastrointestinal transit a randomized controlled study
    Clinical Gastroenterology and Hepatology, 2005
    Co-Authors: Jonathan Gonenne, Michael Camilleri, Bruce Wallin, Irene Ferber, Duane Burton, Kari Baxter, Kian Keyashian, Joseph F Foss, Alan R Zinsmeister
    Abstract:

    Background & Aims: Opiate bowel dysfunction is a significant clinical problem. Our aim was to evaluate the ability of a peripheral μ-opioid antagonist, Alvimopan, to reverse the effect of codeine on gastric, small-bowel, and colonic transit time in healthy volunteers. Methods: Seventy-four healthy participants (43 women) were randomized in a double-blind, placebo-controlled manner to 1 of 4 groups: Alvimopan 12 mg twice daily in the presence and absence of codeine sulfate 30 mg 4 times/day, or codeine or placebo alone. Gastric emptying, small-bowel, and colonic transit were measured by scintigraphy using a 99m-labeled technetium egg meal and 111-labeled indium charcoal delivered to the proximal colon via a delayed-release capsule. The primary end points for colonic transit were geometric center of the colonic counts at 24 hours and time for 50% ascending colon emptying. Analysis of covariance was used to assess the significance of the primary and secondary end points. Results: Codeine delayed gastric, small-bowel, proximal, and overall colonic transit ( P P P Conclusions: Alvimopan reverses codeine's inhibitory effect on small-bowel and colon transit and has potential for treatment of opiate bowel dysfunction. Alvimopan alone accelerates colonic transit, suggesting that μ-opiate mechanisms participate in the physiologic control of colonic transit.

  • phase iii trial of Alvimopan a novel peripherally acting mu opioid antagonist for postoperative ileus after major abdominal surgery
    Diseases of The Colon & Rectum, 2005
    Co-Authors: Conor P Delaney, Lee Techner, James L. Weese, Neil Hyman, Joel J Bauer, Kathie Gabriel, William K Schmidt, Bruce Wallin
    Abstract:

    PURPOSE: Postoperative ileus presents significant clinical challenges that potentially prolong hospital stay, contribute to readmission, and increase morbidity. There is no approved treatment for postoperative ileus. Alvimopan is a novel, peripherally acting, mu opioid receptor antagonist currently in development for the management of postoperative ileus. METHODS: Patients undergoing partial colectomy or simple or radical hysterectomy were randomized to receive Alvimopan 6 mg (n = 152), Alvimopan 12 mg (n = 146), or placebo (n = 153) orally 2 hours before surgery and twice daily thereafter until discharge or for up to seven days. The primary efficacy end point, time to return of gastrointestinal function, was a composite measure of passage of flatus or stool and tolerating solid food. Secondary end points included time to the hospital discharge order written. Adverse events were monitored throughout the study. RESULTS: Mean time to gastrointestinal recovery was significantly reduced in patients treated with Alvimopan 6 mg vs. placebo (hazard ratio = 1.45; P = 0.003), with a smaller reduction seen with Alvimopan 12 mg (hazard ratio = 1.28; P = 0.059). Mean time to the hospital discharge order written was significantly accelerated in patients treated with Alvimopan 6 mg (hazard ratio = 1.50; P < 0.001). The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in the Alvimopan 12-mg group. CONCLUSIONS: In patients undergoing major abdominal surgery, Alvimopan accelerated gastrointestinal recovery and time to the hospital discharge order written compared with placebo and was well tolerated.

Conor P Delaney - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of healthcare use and clinical outcomes of Alvimopan in patients undergoing bowel resection a propensity score matched analysis
    Diseases of The Colon & Rectum, 2018
    Co-Authors: Scott R Steele, Justin T Brady, Zhun Cao, Dorothy Baumer, Scott B Robinson, Keri H Yang, Conor P Delaney
    Abstract:

    BACKGROUND Postoperative ileus is a significant complication after bowel resection surgeries. Alvimopan is the only US Food and Drug Administration-approved therapy for accelerating the return of bowel function after large- and small-bowel resection. OBJECTIVE The purpose of this study was to estimate the healthcare use and in-hospital morbidities associated with on-label use of Alvimopan in patients undergoing bowel resection surgeries. DESIGN A retrospective observational propensity-matched cohort study was conducted using a large hospital administrative database. SETTING The study included inpatient postsurgical patients. PATIENTS Patients aged ≥18 years undergoing a primary large or small segmental bowel resection with discharge dates between January 2010 and December 2014 were included. INTERVENTIONS Patients receiving 2 to 15 doses of Alvimopan were defined as the treatment cohort, and those without any Alvimopan use were included as control subjects. MAIN OUTCOME MEASURES The primary outcome was postoperative length of stay. Secondary outcomes included postoperative in-hospital morbidities, inpatient mortality, intensive care unit length of stay, discharge disposition, and 30-day readmission. RESULTS Each propensity-score matched cohort included 18,559 patients. The mean (±SD) postoperative length of stay was 4.62 ± 2.45 days in Alvimopan-treated patients compared with 5.24 ± 3.35 days in control subjects (p < 0.001). Alvimopan-treated patients had lower rates of postoperative GI complication (12.15% vs 16.50%; p < 0.001). The rates of urinary tract infections; other postoperative infections; and cardiovascular, pulmonary, thromboembolic, and cerebrovascular events were also lower compared with the control subjects. LIMITATIONS The study was limited by its inability to generalize to the US population, because the database included a convenience sample of hospital discharges. The identification of patients undergoing bowel resection and their clinical conditions relied on the accuracy and completeness of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedure coding. There may be a confounding effect by the use of enhanced recovery pathways associated with the use of Alvimopan. CONCLUSIONS The use of Alvimopan was associated with a reduction of 0.62 days in postsurgery length of stay and lower rates of postoperative GI complications, infections, and other in-hospital morbidities. See Video Abstract at http://links.lww.com/DCR/A703.

  • Alvimopan in the setting of colorectal resection with an ostomy to use or not to use
    Surgical Endoscopy and Other Interventional Techniques, 2017
    Co-Authors: Yuxiang Wen, Conor P Delaney, Murad A Jabir, Michael Keating, Alison R Althans, Justin T Brady, Bradley J Champagne, Scott Steele
    Abstract:

    Postoperative ileus (POI) is a major cause of morbidity, increased length of stay (LOS) and hospital cost after colorectal surgery. Alvimopan is a µ-opioid antagonist used to accelerate upper and lower gastrointestinal function after bowel resection. We hypothesized that Alvimopan would reduce LOS in patients undergoing colorectal resection with stoma, a situation that has not been evaluated. A retrospective review (2010–2015) identified 58 patients who underwent colorectal resection for benign or malignant disease with stoma creation and received Alvimopan. They were case-matched to 58 non-Alvimopan patients based on age, BMI, baseline comorbidities, stoma type created and surgical approach. We compared overall LOS, incidence of POI and other postoperative complications. There were equal numbers of laparoscopic (N = 18) and open resections (N = 40) in the Alvimopan group and non-Alvimopan group. There were also equal numbers of patients with an ileostomy (N = 37) or colostomy (N = 21) in each group. Overall, 41 patients underwent resection for malignant disease in the Alvimopan group compared to 37 in the non-Alvimopan group. There was a significant reduction in median LOS overall (Alvimopan 5 (4–7) versus control 6 (4.75–9.25) days, P = 0.03). While the 6-day median LOS was similar for patients undergoing ileostomy creation (P = 0.25), Alvimopan patients had a 3-day decreased median LOS that approached statistical significance (P = 0.06). The overall 30-day complication rate was higher in the control group (41.4 vs. 51.7%, P = 0.26), but the readmission rate within 30 days was higher in the Alvimopan group (19 vs. 13.8%, P = 0.45). Neither of these differences reached statistically significance. The use of Alvimopan in patients undergoing colorectal resection with stoma is associated with a significantly shorter LOS, but the increased readmission rate warrants further study. Based on these data, Alvimopan should be evaluated in a controlled setting for patients undergoing colorectal resection with colostomy creation.

  • the use of Alvimopan for postoperative ileus in small and large bowel resections
    Expert Review of Gastroenterology & Hepatology, 2015
    Co-Authors: Justin T Brady, Benjamin P Crawshaw, Scott R Steele, Eslam Dosokey, Conor P Delaney
    Abstract:

    Transient ileus is a normal physiologic process after surgery. When prolonged, it is an important contributor to postoperative complications, increased length of stay and increased healthcare costs. Efforts have been made to prevent and manage postoperative ileus; Alvimopan is an oral, peripheral μ-opioid receptor antagonist, and the only currently US FDA-approved medication to accelerate the return of gastrointestinal function postoperatively.

  • Alvimopan and enhanced recovery pathways in colorectal surgery
    Clinical investigation, 2014
    Co-Authors: Benjamin P Crawshaw, Deborah S Keller, Conor P Delaney
    Abstract:

    Postoperative ileus negatively impacts patient outcomes and healthcare utilization, increasing both postoperative length of stay and health care costs. In efforts to optimize perioperative care, efforts have been placed into developing tools to minimize postoperative ileus. Alvimopan (Entereg®) was developed to meet this need. Alvimopan has permitted accelerated return of bowel function after abdominal surgery in select patients. Alvimopan has the potential to significantly improve clinical and financial results, and research is ongoing to determine effective further applications of this medication.

  • REVIEW Management of postoperative ileus: focus on Alvimopan
    2013
    Co-Authors: Eric Marderstein, Conor P Delaney
    Abstract:

    Abstract: Postoperative ileus (POI) is a transient loss of coordinated peristalsis precipitated by surgery and exacerbated by opioid pain medication. Ileus causes a variety of symptoms including bloating, pain, nausea, and vomiting, but particularly delays tolerance of oral diet and liquids. Thus POI is a primary determinant of hospital stay after surgery. ‘Fast-track ’ recovery protocols, opioid sparing analgesia, and laparoscopic surgery reduce but do not eliminate postoperative ileus. Alvimopan is a mu opioid receptor antagonist that blocks the effects of opioids on the intestine, while not interfering with their centrally mediated analgesic effect. Several large randomized clinical trials have demonstrated that Alvimopan accelerates the return of gastrointestinal function after surgery and subsequent hospital discharge by approximately 20 hours after elective open segmental colectomy. However, it has not been tested in patients undergoing laparoscopic surgery and is less effective in patients receiving nonsteroidal antiinflammatory agents in a narcotic sparing postoperative pain control regimen. Safety concerns seen with chronic low dose administration of Alvimopan for opioid bowel dysfunction have not been noted with its acute use for POI

Christi S Kleoudis - One of the best experts on this subject based on the ideXlab platform.

  • a randomized placebo controlled phase 3 trial study sb 767905 012 of Alvimopan for opioid induced bowel dysfunction in patients with non cancer pain
    The Journal of Pain, 2011
    Co-Authors: Jan Peter Jansen, Ben Lasko, Amy Pierce, Christi S Kleoudis, Jerry Snidow, John I Wurzelmann, Daniel Lorch, John Langan, Kai Hermanns, E Mortensen
    Abstract:

    Abstract Gastrointestinal (GI) side effects are common with opioid medication, and constipation affects ∼40% of patients. Such symptoms considerably impair patients' quality of life. Alvimopan is an orally administered, systemically available, peripherally acting mu-opioid receptor (PAM-OR) antagonist approved in the US for short-term, in-hospital management of postoperative ileus in patients undergoing bowel resection. This double-blind, placebo-controlled trial was conducted as part of a recently discontinued clinical program, in which Alvimopan was being developed for opioid-induced constipation (OIC). Patients (N = 518) receiving opioids for non-cancer pain were randomized to receive Alvimopan .5 mg once daily, Alvimopan .5 mg twice daily, or placebo for 12 weeks. The primary efficacy endpoint was the proportion of patients experiencing ≥3 spontaneous bowel movements (SBMs; bowel movements with no laxative use in the previous 24 hours) per week over the treatment period and an average increase from baseline of ≥1 SBM per week. A significantly greater proportion of patients in the Alvimopan .5 mg twice-daily group met the primary endpoint compared with placebo (72% versus 48%, P P Perspective These results demonstrate the potential for a PAM-OR antagonist to improve the symptoms of OIC without antagonizing opioid analgesia.

  • a randomized placebo controlled phase 3 trial study sb 767905 013 of Alvimopan for opioid induced bowel dysfunction in patients with non cancer pain
    The Journal of Pain, 2011
    Co-Authors: Gordon Irving, Amy Pierce, Christi S Kleoudis, Janos Penzes, Brian Ramjattan, Michael J Cousins, Richard Rauck, Egilius L H Spierings, Jerry Snidow, John I Wurzelmann
    Abstract:

    Abstract The balance between the pain relief provided by opioid analgesics and the side effects caused by such agents is of particular significance to patients who take opioids for the long-term relief of non-cancer pain. The spectrum of signs and symptoms affecting the gastrointestinal (GI) tract associated with opioid use is known as opioid-induced bowel dysfunction. Alvimopan is an orally administered, systemically available, peripherally acting mu-opioid receptor (PAM-OR) antagonist, approved in the US for the management of postoperative ileus in patients undergoing bowel resection (short-term, in-hospital use only). Alvimopan was under clinical development for long-term treatment of opioid-induced constipation (OIC) but this program has been discontinued. This double-blind, placebo-controlled trial, part of the former OIC development program, enrolled patients (N = 485) receiving opioids for non-cancer pain. Patients were randomized to receive Alvimopan .5 mg once daily, Alvimopan .5 mg twice daily, or placebo, for 12 weeks. The primary efficacy endpoint was the proportion of patients who experienced ≥3 spontaneous bowel movements (SBMs; bowel movements with no laxative use in the previous 24 hours) per week over the treatment period, and an average increase from baseline of ≥1 SBM per week. There were greater proportions of SBM responders in both Alvimopan treatment groups (63% in both groups) compared with placebo (56%), although these differences were not statistically significant. Secondary efficacy analyses indicated that Alvimopan was numerically superior to placebo in improving opioid-induced bowel dysfunction symptoms and patients' global assessment of opioid-induced bowel dysfunction, and reduced the requirement for rescue laxatives. Active treatment was well tolerated and Alvimopan did not antagonize opioid analgesia. Perspective Although the primary endpoint was not met in this study, the magnitude of Alvimopan-induced improvements versus baseline, together with previous study results, suggest that a PAM-OR antagonist has the potential to improve OIC.

  • Alvimopan a peripherally acting mu opioid receptor pam or antagonist for the treatment of opioid induced bowel dysfunction results from a randomized double blind placebo controlled dose finding study in subjects taking opioids for chronic non cancer pain
    Pain, 2008
    Co-Authors: Lynn R Webster, Jan Peter Jansen, John F Peppin, Ben Lasko, Gordon Irving, Bart Morlion, J Snidow, Amy Pierce, E Mortensen, Christi S Kleoudis
    Abstract:

    Our objective was to investigate the efficacy and safety of Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, in subjects with non-cancer pain and opioid-induced bowel dysfunction (OBD), and to identify at least one treatment regimen that improves OBD. Following a 2-week baseline period, 522 subjects reporting or=25% accompanied by a sensation of incomplete evacuation, straining, or lumpy hard stools), requiring analgesia equivalent to >or=30 mg oral morphine/day were randomized to Alvimopan 0.5mg twice daily (BID), 1mg once daily (QD), 1mg BID, or placebo for 6 weeks. Compared with placebo, there was a statistically and clinically significant increase in mean weekly SBM frequency over the initial 3 weeks of treatment (primary endpoint) with Alvimopan 0.5mg BID (+1.71 mean SBMs/week), Alvimopan 1mg QD (+1.64) and Alvimopan 1mg BID (+2.52); P<0.001 for all comparisons. Increased SBM frequency and additional treatment effects, including improvements in symptoms such as straining, stool consistency, incomplete evacuation, abdominal bloating/discomfort, and decreased appetite, were sustained over 6 weeks. The most frequently reported adverse events were abdominal pain, nausea, and diarrhea, occurring more frequently in the higher dosage groups. The Alvimopan 0.5mg BID regimen demonstrated the best benefit-to-risk profile for managing OBD with Alvimopan in this study population, with a side effect profile similar to that of placebo. There was no evidence of opioid analgesia antagonism. Competitive peripheral antagonism of opioids with Alvimopan can restore GI function and relieve OBD without compromising analgesia.

  • Alvimopan a peripherally acting mu opioid receptor pam or antagonist for the treatment of opioid induced bowel dysfunction results from a randomized double blind placebo controlled dose finding study in subjects taking opioids for chronic non cancer pain
    Pain, 2008
    Co-Authors: Lynn R Webster, Jan Peter Jansen, John F Peppin, Ben Lasko, Gordon Irving, Bart Morlion, J Snidow, Amy Pierce, E Mortensen, Christi S Kleoudis
    Abstract:

    Abstract Our objective was to investigate the efficacy and safety of Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, in subjects with non-cancer pain and opioid-induced bowel dysfunction (OBD), and to identify at least one treatment regimen that improves OBD. Following a 2-week baseline period, 522 subjects reporting

E Mortensen - One of the best experts on this subject based on the ideXlab platform.

  • a randomized placebo controlled phase 3 trial study sb 767905 012 of Alvimopan for opioid induced bowel dysfunction in patients with non cancer pain
    The Journal of Pain, 2011
    Co-Authors: Jan Peter Jansen, Ben Lasko, Amy Pierce, Christi S Kleoudis, Jerry Snidow, John I Wurzelmann, Daniel Lorch, John Langan, Kai Hermanns, E Mortensen
    Abstract:

    Abstract Gastrointestinal (GI) side effects are common with opioid medication, and constipation affects ∼40% of patients. Such symptoms considerably impair patients' quality of life. Alvimopan is an orally administered, systemically available, peripherally acting mu-opioid receptor (PAM-OR) antagonist approved in the US for short-term, in-hospital management of postoperative ileus in patients undergoing bowel resection. This double-blind, placebo-controlled trial was conducted as part of a recently discontinued clinical program, in which Alvimopan was being developed for opioid-induced constipation (OIC). Patients (N = 518) receiving opioids for non-cancer pain were randomized to receive Alvimopan .5 mg once daily, Alvimopan .5 mg twice daily, or placebo for 12 weeks. The primary efficacy endpoint was the proportion of patients experiencing ≥3 spontaneous bowel movements (SBMs; bowel movements with no laxative use in the previous 24 hours) per week over the treatment period and an average increase from baseline of ≥1 SBM per week. A significantly greater proportion of patients in the Alvimopan .5 mg twice-daily group met the primary endpoint compared with placebo (72% versus 48%, P P Perspective These results demonstrate the potential for a PAM-OR antagonist to improve the symptoms of OIC without antagonizing opioid analgesia.

  • Alvimopan a peripherally acting mu opioid receptor pam or antagonist for the treatment of opioid induced bowel dysfunction results from a randomized double blind placebo controlled dose finding study in subjects taking opioids for chronic non cancer pain
    Pain, 2008
    Co-Authors: Lynn R Webster, Jan Peter Jansen, John F Peppin, Ben Lasko, Gordon Irving, Bart Morlion, J Snidow, Amy Pierce, E Mortensen, Christi S Kleoudis
    Abstract:

    Our objective was to investigate the efficacy and safety of Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, in subjects with non-cancer pain and opioid-induced bowel dysfunction (OBD), and to identify at least one treatment regimen that improves OBD. Following a 2-week baseline period, 522 subjects reporting or=25% accompanied by a sensation of incomplete evacuation, straining, or lumpy hard stools), requiring analgesia equivalent to >or=30 mg oral morphine/day were randomized to Alvimopan 0.5mg twice daily (BID), 1mg once daily (QD), 1mg BID, or placebo for 6 weeks. Compared with placebo, there was a statistically and clinically significant increase in mean weekly SBM frequency over the initial 3 weeks of treatment (primary endpoint) with Alvimopan 0.5mg BID (+1.71 mean SBMs/week), Alvimopan 1mg QD (+1.64) and Alvimopan 1mg BID (+2.52); P<0.001 for all comparisons. Increased SBM frequency and additional treatment effects, including improvements in symptoms such as straining, stool consistency, incomplete evacuation, abdominal bloating/discomfort, and decreased appetite, were sustained over 6 weeks. The most frequently reported adverse events were abdominal pain, nausea, and diarrhea, occurring more frequently in the higher dosage groups. The Alvimopan 0.5mg BID regimen demonstrated the best benefit-to-risk profile for managing OBD with Alvimopan in this study population, with a side effect profile similar to that of placebo. There was no evidence of opioid analgesia antagonism. Competitive peripheral antagonism of opioids with Alvimopan can restore GI function and relieve OBD without compromising analgesia.

  • Alvimopan a peripherally acting mu opioid receptor pam or antagonist for the treatment of opioid induced bowel dysfunction results from a randomized double blind placebo controlled dose finding study in subjects taking opioids for chronic non cancer pain
    Pain, 2008
    Co-Authors: Lynn R Webster, Jan Peter Jansen, John F Peppin, Ben Lasko, Gordon Irving, Bart Morlion, J Snidow, Amy Pierce, E Mortensen, Christi S Kleoudis
    Abstract:

    Abstract Our objective was to investigate the efficacy and safety of Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, in subjects with non-cancer pain and opioid-induced bowel dysfunction (OBD), and to identify at least one treatment regimen that improves OBD. Following a 2-week baseline period, 522 subjects reporting