Subcutaneous Methylnaltrexone for the Treatment of Opioid-Induced Constipation in Patients with Advanced Illness: A Double-Blind, Randomized, Parallel Group, Dose- Ranging Study  Russell K. Portenoy, MD, Jay Thomas, MD, PhD, Michele L. Moehl Boatwright, MD, Diep Tran, MS, Frank L. Galasso, MS, Nancy Stambler, MS, Charles F. Von Gunten, MD, PhD, Robert J. Israel, MD  Journal of Pain and Symptom Management  Volume 35, Issue 5, Pages 458-468 (May 2008) DOI: 10.1016/j.jpainsymman.2007.12.005 Copyright © 2008 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 1 Patient disposition. Of 39 patients screened, 33 met eligibility criteria and received one or more doses of the study drug (intent-to-treat and safety populations). One-third of these patients (n=11) discontinued the study during the double-blind phase. The most common reason for discontinuation during the double-blind phase was “patient request” (n=7), and only one patient discontinued in response to an intolerable adverse event. *One patient received all three doses during the double-blind phase but withdrew from the study without completing the 30-day follow-up period intended by the protocol. Journal of Pain and Symptom Management 2008 35, 458-468DOI: (10.1016/j.jpainsymman.2007.12.005) Copyright © 2008 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 2 Laxation within four hours of dose (mg/kg): double-blind period. The proportion of patients who reported a laxation response within four hours during the double-blind phase, as grouped by weight-adjusted dose categories, is shown. Journal of Pain and Symptom Management 2008 35, 458-468DOI: (10.1016/j.jpainsymman.2007.12.005) Copyright © 2008 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 3 Time to laxation: all double-blind doses (mg) (Kaplan-Meier estimates). The median time to laxation for the 1, 5, 12.5, and 20mg dose groups are visualized in line plots of laxation response vs. time, post-dosing. Journal of Pain and Symptom Management 2008 35, 458-468DOI: (10.1016/j.jpainsymman.2007.12.005) Copyright © 2008 U.S. Cancer Pain Relief Committee Terms and Conditions