Characterization of Abdominal Pain During Methylnaltrexone Treatment of Opioid- Induced Constipation in Advanced Illness: A Post Hoc Analysis of Two Clinical Trials  Neal E. Slatkin, MD, Richard Lynn, MD, Chinyu Su, MD, Wenjin Wang, PhD, Robert J. Israel, MD  Journal of Pain and Symptom Management  Volume 42, Issue 5, Pages 754-760 (November 2011) DOI: 10.1016/j.jpainsymman.2011.02.015 Copyright © 2011 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 1 Study designs of two double-blind, placebo-controlled, Phase III trials in patients with advanced illness and opioid-induced constipation. ∗Dose escalation was allowed at the discretion of the primary investigator in patients with fewer than three rescue-free bowel movements by Day 8. OL=open label; QOD=every other day; SC=subcutaneous. Journal of Pain and Symptom Management 2011 42, 754-760DOI: (10.1016/j.jpainsymman.2011.02.015) Copyright © 2011 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 2 Incidence of abdominal pain AEs in methylnaltrexone-treated patients across double-blind and open-label phases of Studies 1 and 2. An abdominal pain AE for any given dose occurred after that dose and before the next dose, unless the given dose was the last dose received. In that case, the abdominal pain AE occurred between dose administration and 30 days thereafter. aRepresents the dose number of methylnaltrexone a patient received. For example, the first open-label dose of methylnaltrexone for a patient who previously received double-blind placebo would be considered Dose 1, whereas the first open-label dose of methylnaltrexone for a patient who previously received seven double-blind methylnaltrexone doses would be considered Dose 8. Journal of Pain and Symptom Management 2011 42, 754-760DOI: (10.1016/j.jpainsymman.2011.02.015) Copyright © 2011 U.S. Cancer Pain Relief Committee Terms and Conditions