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Supplementary AppendixThis appendix has been provided by the authors to give readers additional information about their work.Supplement to: Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 2011;364:22-32.

Figure 1A. The percentage of patients in each group with adequate relief of Global-IBSsymptoms in TARGET 1 (p 0.02). The p-value represents improvement demonstrated byrifaximin treatment for the 12 week period on the outcome of the percentage whoachieved adequate relief of IBS symptoms for at least one week every two-week period.P-value is calculated based on a repeated measures analysis using a generalizedestimating equation model with fixed effects for the following variables: treatment;analysis center; and week.1

Figure 1B. The percentage of patients in each group with adequate relief of Global-IBSsymptoms in TARGET 2 (p 0.02). The p-value represents improvement demonstrated byrifaximin treatment for the 12 week period on the outcome of the percentage whoachieved adequate relief of IBS symptoms for at least one week every two-week period.P-value is calculated based on a repeated measures analysis using a generalizedestimating equation model with fixed effects for the following variables: treatment;analysis center; and week.2

Online Supplement: Sensitivity AnalysesTable A: Sensitivity Analyses on the Primary Efficacy Endpoint: Adequate Relief ofGlobal IBS Symptoms (TARGET 1 and TARGET 2)TARGET 1Primary Efficacy EndpointObserved Cases AnalysisAdequate Relief of global IBSSymptoms – ITT PopulationRespondersNonrespondersMultiple Imputation AnalysisAdequate Relief of global IBSSymptoms – ITT PopulationRespondersNonrespondersTARGET 2TxTxRFX Placebo p-value Effect RFX Placebo p-value %33%67%32%68%10%0.026441%59%8%8%33%67%Table B: Sensitivity Analyses on the Key Secondary Efficacy Endpoint: AdequateRelief of IBS-Bloating (TARGET 1 and TARGET 2)TARGET 1Key Secondary Efficacy EndpointObserved Cases AnalysisAdequate Relief of Bloating –ITT PopulationRespondersNonrespondersMultiple Imputation AnalysisAdequate Relief of Bloating –ITT PopulationRespondersNonrespondersTARGET 2TxTxRFX Placebo p-value Effect RFX Placebo p-value %38%0.02039%32%68%11%42%58%0.032233%67%

Online supplement Figure 2: Global IBS symptoms: Mean Change from Baseline inAverage Daily Score: Combined Data from TARGET 1 & TARGET 24

Online supplement Figure 3: IBS-related Bloating: Mean Change from Baseline inAverage Daily Score: Combined Data from TARGET 1 & TARGET 25

Online supplement Figure 4: IBS-related Abdominal Pain and Discomfort: MeanChange from Baseline in Average Daily Score: Combined Data from TARGET 1 &TARGET 26

Online supplement Figure 5: Stool Consistency: Mean Change from Baseline inAverage Daily Score: Combined Data from TARGET 1 & TARGET 27

Online supplement Figure 6: Percentage of Days with Stool Urgency: Mean Changefrom Baseline in Average Daily Score: Combined Data from TARGET 1 &TARGET 28

AppendixThe participants in the TARGET Study Group were as follows: M. Alexander; NiagaraClinical Research, Niagara Falls, CAN - L. Alwine; Brandywine Clinical Research,Downingtown, PA - R. Anspach; Tatum Highlands Medical Associates, Phoenix, AZ - D.Armstrong; McMaster Medical Center Health Science 3 WIZ, Hamilton, ON - K. Ashby;Therapeutic Research Institute of Orange County, Laguna Hills, CA - L. Banker;Carolina Research Trials, PC, New Bern, NC - T. Barker; Research Institute of theCarolinas, PLLC, Mooresville, NC - M. Baron; Rapid Medical Research, Inc., Cleveland,OH - C. Baum; Cotton O'Neil Digestive Health Center, Topeka, KS - R. Bennetts;Northwest Gastroenterology Clinic, Portland, OR - R. Beyer; Women's Health CareSpecialists, P.C., Paw Paw, MI - B. Bhandari; Gastroenterology Clinic, Monroe, LA - F.Braunstein; Upstate Gastroenterology Associates, Troy, NY - E. Bretton; AlbuquerqueClinical Trials, Inc., Albuquerque, NM - K. Brown; Digestive Health Associates, Plano,TX - R. Burakoff; Brigham and Women's Hospital, Boston, MA - E. Burbige; John MuirPhysician Network Clinical Research Center, Concord, CA - W. Burch; FranklinGastroenterology, Franklin, TN - D. Callaghan; Callaghan Denis, Hamilton, ON - J.Cappleman; CEC Research, Inc, Winter Garden, FL - M. Castillo; Hidalgo ClinicalResearch, LLC, San Antonio, TX - S. Challa; Kansas Medical Center, Topeka, KS - T.Chami; Florida Medical Clinic, P.A., Zephyrhills, FL - M. Chilvers; Sarnia ResearchInstitute, Sarnia, ON - L. Clark; Gastroenterology Associates, Greensboro, NC - A.Coates; Gastroenterology Associates of Western Michigan, P.L.C., Wyoming, MI - A.Coppola; Little Rock Diagnostic Clinic, Little Rock, AR - I. Crespo; Advanced ResearchInstitute, Trinity, FL - D. Crowley; KGK Synergize Inc., London, - S. Daly; Salt Lake9

Research, Inc., Salt Lake City, UT - J. D'Ambrosio; Kalamazoo Center for Med,Kalamazoo, MI - D. D'Auria; D'Auria, Daniel A., Sicklerville, NJ - G. Davis; LynnInstitute of the Ozarks, Little Rock, AR - J. Davis; Hope Research Institute, Phoenix, AZ- M. DiGiovanna; DiGiovanna Institute for Medical Education & Research, N.Massapequa, NY - G. Doering; Spokane Internal Medicine, Spokane Valley, WA - D.Dozer; Discovery Research International, LLC, West Bend, WI - D. Dulitz; ClinicalTrials Management, Meltairie, LA - S. Dunmyer; Pharmacotherapy Research Associates,Inc., Zanesville, OH - M. Dupree; Consultants for Clinical Research of South Florida,Boynton Beach, FL - W. Emlich; Remington-Davis, Inc., Columbus, OH - S. Esposito;Hepatobiliary Associates of New York, Bayside, NY - C. Farrington; Crescent MedicalResearch, Salisbury, NC - S. Fein; Digestive Health Center, Pasadena, TX - N. Ferreira;The Center for Clinical Research at Washington County Hospital, Hagerstown, MD - S.Finkelstein; Advanced Medical Research, LLC, Lakewood, CA - L. Freeman; DigestiveHealth Specialists of Tyler, Tyler, TX - B. Fung Liu; Long Island Clinical ResearchAssociates, Great Neck, NY - W. Futch; Southern Gastroenterology Associates, NewBern, NC - S. Gaddam; Digestive & Liver Disease Spec, Garden Grove, CA - T. Gardner;Northside Internal Medicine, Spokane, WA - M. Gaspari; Metrolina Medical Research,Charlotte, NC - D. Geenen; Wisconsin Center for Advanced Research, Milwaukee, WI C. Goetsch; Clinical Research Associates, LLC, Huntsville, AL - G. Gordon; Center forDigestive and Liver Diseases, Inc., Mexico, MO - P. Gupta; Gastrointestinal & LiverDisease Consultants, Dayton, OH - D. Gutman; Progressive GastroenterologyConsultants, Mineola, NY - C. Hall; CRC of Jackson, Jackson, MS - A. Harris; Harris &Associates, Detroit, MI - A. Hemaidan; Advanced Medical Research Center, Port Orange,10

FL - S. Henein; Dr. Sam Henein & Associates, Newmarket, - C. Herring; New HanoverMedical Research, Wilmington, NC - J. Herrod; Cochise Clinical Research, Sierra Vista,AZ - C. Hertz; Medical Speciality Clinic, Jackson, TN - R. Hilal; Center for AdvancedGastroenterology, Maitland, FL - D. Homoky; Gastroenterology Associates, Kinsport,TN - K. Horton; IMED Research, PA, San Antonio, TX - S. Ibarra; Research AcrossAmerica - El Paso, El Paso, TX - J. Izanec; Allied Gastrointestinal Associates, Voorhees,NJ - P. Jaffe; Medical Research Center of Connecticut, Hamden, CT - R. Jain; RockyMountain Gastroenterology Associates, Lakewood, CO - V. Jayanty; Houston Endoscopyand Research Center, Inc., Houston, TX - R. Kaplan; LeBauer Research Associates, P.A.,Greensboro, NC - P. Kashyap; Pinnacle Research Group, LLC - Central, Anniston, AL B. Katz; Digestive Disease Consultants of South Florida, Altamonte Spring, FLs - M.Khandelwal; Mukul Khandelwal's Private Practice, Elkridge, MD - J. Kirstein; AdvancedClinical Research (ACR), West Jordan, UT - W. Knapple; Arkansas Gastroenterology,P.A., Sherwood, AR - M. Koch; Capital Gastroenterology Consultants, P.A., SilverSpring, MD - V. Kodali; Cumberland Research Associates, LLC, Fayetteville, NC - W.Koltun; Medical Center for Clinical Research, San Diego, CA - G. Koval; West HillsGastroenterology Research, Portland, OR - R. Krause; ClinSearch, Chattanooga, TN - G.Kubala; Medical Research Unlimited, Cincinnati, OH - B. Lacy; Dartmouth-HitchcockMedical Center, Lebanon, NH - M. Lamet; Mark Lamet, MD, Hollywood, FL - G.Lefebvre; Meridien Research, St. Petersburg, FL - S. Levenson; Digestive Care MedicalCenter, San Carlos, CA - D. Lewis; Arkansas Primary Care Clinic, PA, Little Rock, AR R. Lindenberg; Litchfield County Gastroenterology Associates, LLC, Torrington, CT - I.Lopez; Gastroenterology & Nutrition Specialist, P.A., Orlando, FL - J. Lowe; Advanced11

Research Institute, Ogden, UT - D. Luba; Gastroenterology Consultants, Monterey, CA R. Luton; Oxford AIM Clinic, London, - D. Maico; Southeastern Integrated Medical, PL,Gainesville, FL - P. Malik; Gastroenterology Associates of Tidewater, Chesapeake, VA N. Manji; Pioneer Research Solutions, Houston, TX - I. Marcadis; Palm Beach ResearchCenter, West Palm Beach, FL - R. McCallum; Kansas University Medical Center, KansasCity, KS - T. McDonald; Guthrie Clinic Ltd, Sayre, PA - J. Medoff; Vital Research,Greensboro, NC - P. Milner; Gastrointestinal Associates, PA, Jackson, MS - K. Mirkin;Gastroenterology and Hepatology Consultants of Northern Virg, Fairfax, VA - K. Misik;Topsail Road Medical Clinic, St. John's, NF - D. Morgan; St. Joseph's HealthcareHamilton, Hamilton, ON - P. Moses; University of Vermont, Burlington, VT - M.Nagrani; United Medical Research Institute, New Smyrna Beach, FL - F. Nammour;Innovis Health, Fargo, ND - V. Narayen; Digestive Disease Associates, P.A., Baltimore,MD - M. Oberoi; Central Jersey Health Care, LLC, Elizabeth, NJ - A. Ojuri; WestGastroenterology Group, Murrietta, CA - W. O'Mahony; Corunna Research Centre,Corunna, ON - F. Opper; Hanover Medical Specialists, P.A., Wilmington, NC - G. Orr;Greensboro Medical Associates, Greensboro, NC - T. Patrick; Dayton Science Institute,Dayton, OH - L. Peters; Peters Medical Research, High Point, NC - R. Phillips;Gastroenterology Group of Naples, Naples, FL - M. Pimentel; Cedars-Sinai MedicalCenter, Los Angeles, CA - A. Poch; Louisiana Research Center, LLC, Shreveport, LA - S.Powell; Tri-Cities Medical Research, Bristol, TN - J. Pruthi; High DesertGastroenterology, Inc., Lancaster, CA - L. Quallich; Center for Digestive Health, Troy,MI - C. Randall; Gastroenterology Clinic of San Antonio, San Antonio, TX - D. Rauh;Graves Gilbert Clinic, Bowling Green, KY - M. Raza; Elkhart Clinic, Elkhart, IN - R.12