Impact of Patient Subgroups on the Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients with Advanced Illness.

Purpose: We evaluated the impact of baseline patient characteristics on safety and efficacy of methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, in patients with advanced illness with opioid-induced constipation (OIC).

Patients And Methods: This analysis pooled data from 2 randomized, double-blind, placebo-controlled studies (study 302: NCT00402038; study 4000: NCT00672477) in patients with advanced illness, including cancer, and OIC. Patients were randomized to receive subcutaneous methylnaltrexone (study 302: 0.

Methylnaltrexone Treatment for Opioid-Induced Constipation in Patients with and without Cancer: Effect of Initial Dose.

Purpose: Opioid-induced constipation (OIC) is a common side effect of opioid therapy. Methylnaltrexone (MNTX) is a selective, peripherally acting μ-opioid receptor antagonist, with demonstrated efficacy in treating OIC. We pooled results from MNTX clinical trials to compare responses to an initial dose in patients with chronic cancer and noncancer pain.

Cumulative Laxation Response with Methylnaltrexone: Implications for Hospitalized Patients with Advanced Illness and Opioid-Induced Constipation.

Background: Opioid-induced constipation (OIC) may increase the risk of fecal impaction and mortality in patients with advanced illness. Methylnaltrexone (MNTX) is efficacious for OIC.

Objective: The purpose of this analysis was to evaluate cumulative rescue-free laxation response with repeat MNTX dosing in patients with advanced illness who were refractory to current laxative regimens and to assess the influence, if any, of poor functional status on response to MNTX treatment.

A Randomized, Double-Blind, Parallel Design Thorough QT Study With a Nested Crossover to Compare the Cardiac Safety of Amiselimod With Placebo and Positive Control in Healthy Volunteers.

This double-blind study evaluated the cardiac safety of amiselimod. Healthy adults (n = 190) were randomized (2:1:1) to receive (1) oral placebo (day -1), followed by oral amiselimod (days 1-26), which was upwardly titrated from 0.4 to 1.

Reductions in All-Cause Mortality Associated with the Use of Methylnaltrexone for Opioid-Induced Bowel Disorders: A Pooled Analysis.

Objective: Preclinical and clinical studies suggest that activation of the µ-opioid receptor may reduce overall survival and increase the risk for all-cause mortality in patients with cancer and noncancer pain. Methylnaltrexone, a selective, peripherally acting µ-opioid receptor antagonist, has demonstrated efficacy for the treatment of opioid-induced constipation. This retrospective analysis of 12 randomized, double-blind, placebo-controlled studies of methylnaltrexone evaluated the treatment of opioid-induced bowel disorders in patients with advanced illness or noncancer pain.

Opioid-Induced Constipation: Cost Impact of Approved Medications in the Emergency Department.

Introduction: Opioid-induced constipation (OIC) prescription medications (OIC-Rx) like methylnaltrexone subcutaneous (SC) have shown efficacy in treating OIC in the emergency department (ED). This study aimed to describe and compare healthcare resource utilization (HRU) and healthcare costs in ED patients with OIC receiving OIC-Rx versus those not receiving OIC-Rx.

Methods: Adult patients with OIC during an ED encounter were identified from a hospital-based ED encounters database (2016-2019) and classified on the basis of receipt of OIC-Rx (OIC-Rx versus No OIC-Rx cohorts).

First-Dose Efficacy of Methylnaltrexone in Patients with Severe Medical Illness and Opioid-Induced Constipation: A Pooled Analysis.

Background: Opioid-induced constipation (OIC) is a frequent consequence of opioid analgesia that may increase patient risk for emergency department visits and hospitalization. Methylnaltrexone is a peripherally acting µ-opioid receptor antagonist indicated for the treatment of OIC.

Objective: To assess the safety and efficacy of a single methylnaltrexone dose.

P029 Pharmacokinetic/Pharmacodynamic Analysis of Amiselimod, a Selective Sphingosine 1-Phosphate Receptor Modulator, in Healthy Subjects: Results From a Phase 1 Study.

Background: Amiselimod is a selective sphingosine 1-phosphate receptor modulator in development for inflammatory bowel disease. It is converted to its active metabolite, amiselimod phosphate (amiselimod-P), and has a long half-life and slow accumulation to steady state. We evaluated a multiple-dose titration regimen to determine the plasma pharmacokinetic (PK) profile of amiselimod and amiselimod-P at steady state for the 0.

Attrition of methylnaltrexone treatment-emergent adverse events in patients with chronic noncancer pain and opioid-induced constipation: a post hoc pooled analysis of two clinical trials.

Opioids prescribed for the management of chronic noncancer pain are associated with nausea, vomiting, and constipation. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, has demonstrated robust efficacy and was well-tolerated in treating opioid-induced constipation without affecting central analgesia. Our objective was to assess changes in the frequency of treatment-emergent adverse events (TEAEs) after the first or second dose of methylnaltrexone or placebo.

Subcutaneous Methylnaltrexone for Treatment of Opioid-Induced Constipation in Cancer versus Noncancer Patients: An Analysis of Efficacy and Safety Variables from Two Studies.

Purpose: Methylnaltrexone inhibits opioid-induced constipation (OIC) by binding to peripheral µ-opioid receptors without impacting central opioid receptor mediated analgesia. This analysis compared methylnaltrexone efficacy and safety among advanced illness patients with and without active cancer and OIC.

Patients And Methods: This post hoc analysis included two multicenter, randomized, double-blind, placebo-controlled studies in adults with advanced illness and OIC who received subcutaneous methylnaltrexone.

The Influence of Age on Central Effects of Methylnaltrexone in Patients with Opioid-Induced Constipation.

Background: Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist approved for the treatment of opioid-induced constipation (OIC), has restricted diffusion across the blood-brain barrier (BBB) and has not been demonstrated to impact opioid-induced central analgesia. Age-related changes in BBB permeability may compromise methylnaltrexone's restricted diffusion and alter opioid-induced central analgesic effects.

Objective: This analysis evaluated whether opioid analgesia is compromised in older adults receiving methylnaltrexone for OIC.

The influence of brain metastases on the central nervous system effects of methylnaltrexone: a post hoc analysis of 3 randomized, double-blind studies.

Purpose: Peripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor) are indicated for the treatment of opioid-induced constipation (OIC). The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC.

Subcutaneous methylnaltrexone for opioid-induced constipation in advanced-illness patients with or without active cancer.

To evaluate methylnaltrexone for opioid-induced constipation in patients with and without cancer. This analysis comprises two Phase III, multicenter, double-blind, randomized studies of advanced-illness patients who received methylnaltrexone subcutaneous injection or placebo. Significantly more patients treated with methylnaltrexone than placebo experienced laxation within 4 (cancer = 55.

Safety of oral methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain.

Purpose: Oral methylnaltrexone was shown to be effective in treating opioid-induced constipation (OIC) in patients with chronic noncancer pain in a Phase III randomized controlled trial. This report provides a detailed safety analysis from that study.

Methods: Adults (n=803) with chronic noncancer pain for ≥2 months and confirmed OIC while receiving opioid doses ≥50 mg morphine equivalent per day for ≥14 days were randomized 1:1:1:1 to oral methylnaltrexone (150, 300, or 450 mg) or placebo once daily for 4 weeks, followed by as-needed use for 8 weeks.

Fulranumab as Adjunctive Therapy for Cancer-Related Pain: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study.

This randomized, double-blind (DB), placebo-controlled, phase 2 study assessed the efficacy and safety of fulranumab as a pain therapy adjunctive to opioids in terminally ill cancer patients. Ninety-eight patients were randomized (2:1) to receive one subcutaneous injection of fulranumab (9 mg) or placebo in the 4-week DB phase. Seventy-one (72%) patients entered the 48-week open-label extension phase and were administered 9 mg of fulranumab every 4 weeks.

Randomized, Double-Blind Trial of Oral Methylnaltrexone for the Treatment of Opioid-Induced Constipation in Patients with Chronic Noncancer Pain.

Background: Subcutaneous methylnaltrexone, a peripherally acting μ-opioid receptor antagonist, improves opioid-induced constipation (OIC) in patients with chronic noncancer pain. An oral methylnaltrexone formulation has been developed.

Methods: In this phase 3, double-blind trial, adults with chronic noncancer pain receiving opioid doses of ≥ 50 mg/day oral morphine equivalents with OIC were randomly assigned to oral methylnaltrexone (150, 300, or 450 mg) or placebo once daily (QD) for 4 weeks followed by as-needed dosing for 8 weeks.

Efficacy and Tolerability of Subcutaneous Methylnaltrexone in Patients with Advanced Illness and Opioid-Induced Constipation: A Responder Analysis of 2 Randomized, Placebo-Controlled Trials.

Background: Subcutaneous methylnaltrexone is efficacious and well tolerated in inducing bowel movements in patients with advanced illness and opioid-induced constipation (OIC); factors determining optimal responsiveness to OIC treatment, however, have not been elucidated. This post hoc responder analysis examined the influence of demographic and baseline characteristics on methylnaltrexone efficacy and tolerability in this population.

Methods: Data were pooled from 2 randomized, double-blind, placebo-controlled, phase 3 studies of subcutaneous methylnaltrexone (0.

Characterization of abdominal pain during methylnaltrexone treatment of opioid-induced constipation in advanced illness: a post hoc analysis of two clinical trials.

Context: Methylnaltrexone is a selective peripherally acting mu-opioid receptor antagonist that decreases the constipating effects of opioids without affecting centrally mediated analgesia. In two double-blind, placebo-controlled, Phase III studies of methylnaltrexone for opioid-induced constipation in patients with advanced illness, abdominal pain was the most common adverse event (AE) reported.

Objectives: This analysis sought to further characterize the Medical Dictionary for Regulatory Activities-defined abdominal pain AEs experienced in these studies.

Long-term tolerability and effectiveness of oxymorphone extended release in patients with cancer.

Objective: To evaluate the long-term safety, tolerability, and effectiveness of oxymorphone extended release (ER) in patients with cancer-related pain.

Design: Post hoc analysis of two-1-year open-label extension studies.

Setting: Multiple US cancer treatment facilities.

Consistent and clinically relevant effects with fentanyl buccal tablet in the treatment of patients receiving maintenance opioid therapy and experiencing cancer-related breakthrough pain.

Fentanyl buccal tablet (FBT) has shown efficacy and tolerability in patients with cancer-related persistent pain treated with maintenance opioids. We conducted a combined analysis of two similarly designed, randomized, placebo-controlled studies to further evaluate the consistency and clinical relevance of analgesia outcomes. Of the 252 patients enrolled, 150 fulfilled the criteria for efficacy analysis and experienced 1,417 breakthrough pain episodes.

Opioid switching and rotation in primary care: implementation and clinical utility.

Background: Opioid therapy is the standard treatment for moderate-to-severe cancer pain and is becoming a more frequent treatment for moderate-to-severe chronic noncancer pain. Response to opioids varies significantly between patients and even within the individual patient at different stages of treatment. Finding an opioid at a dose that provides adequate long-term analgesia with minimal adverse effects can be difficult.

Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients.

Methylnaltrexone, a peripheral mu-opioid receptor antagonist with restricted ability to cross the blood-brain barrier, may relieve opioid-induced constipation (OIC) without reversing analgesia. A total of 154 patients with advanced illness and OIC enrolled in a double-blind, randomized, placebo-controlled trial, with optional open-label phases (up to 4 months) in hospice and palliative care centers during 2003-2005. They received a single subcutaneous injection of methylnaltrexone (0.

Palliative care and pain: new strategies for managing opioid bowel dysfunction.

Opioid analgesics are a cornerstone of pain therapy in the hospice and palliative care population. However, opioid-induced bowel dysfunction (OBD) is a commonly associated condition that frequently compromises the usefulness of these agents. Although its most common and debilitating symptom is constipation, the impact of OBD extends beyond constipation to encompass a myriad of gastrointestinal (GI) signs and symptoms, ranging from decreased gastric emptying and reflux to abdominal pain, cramping, bloating, nausea, and vomiting.