Strategies in Maintenance for Patients Receiving Long-term Therapy (S.I.M.P.L.E.) With MMX (Multi-Matrix System) Mesalamine for Ulcerative Colitis (UC)

A Phase IV, Multi-center, Open-label Study to Assess Clinical Recurrence Related to Compliance With Treatment With MMX Mesalamine 2.4g/Day Given Once Daily for the Maintenance of Quiescent Ulcerative Colitis (UC)

To evaluate the percentage of subjects with clinical recurrence of UC at 6 months using MMX mesalamine once daily.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: MMX Mesalamine

• Study Type: Interventional
• Enrollment (Actual): 290
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Birmingham Gastroenterology Assoc.
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Clopton Clinic
  • California
    • Long Beach, California, United States, 90822
      • VA Medical Center - Long Beach
    • San Diego, California, United States, 92101
      • Sharp Rees-Stealy Medical Group
    • San Diego, California, United States, 92103
      • Clinical Applications Laboratories, Inc.
  • Colorado
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology, P.C.
  • Connecticut
    • Greenwich, Connecticut, United States, 06830
      • The Center for GI Medicine of Fairfield & Westchester, P.C.
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut, LLC
    • New Haven, Connecticut, United States, 06510
      • Connecticut Gastroenterology Associates
  • District of Columbia
    • Washington, District of Columbia, United States, 20307
      • Walter Reed Army Medical Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • Advanced Digestive Care, PA
    • Hollywood, Florida, United States, 33021
      • Southern Clinical Research Consultants
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic
    • New Smyrna Beach, Florida, United States, 32168
      • United Medical Research
    • Palm Harbor, Florida, United States, 34684
      • Advanced Gastroenterology Associates
  • Georgia
    • Decatur, Georgia, United States, 30034
      • Soapstone Ctr. for Clin. Rsrch
    • Macon, Georgia, United States, 31201
      • Gastroenterology Assoc./Cen.GA
    • Marietta, Georgia, United States, 30060
      • NW GA Gastroenterology
  • Illinois
    • Moline, Illinois, United States, 61265
      • Midwest Clinical Research Associates
    • Peoria, Illinois, United States, 61602
      • Accelovance
    • Rockford, Illinois, United States, 61107
      • Rockford Gastroenterology Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital
  • Iowa
    • Davenport, Iowa, United States, 52807
      • Gastrointestinal Clinic of Quad Cities
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • GI Associates
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Louisiana Research Center, LLC
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Maryland Clinical Trials
    • Annapolis, Maryland, United States, 21401
      • Digestive Disorders Associates Research Division
    • Laurel, Maryland, United States, 20707
      • Maryland Digestive Disease Research, Llc
  • Michigan
    • Troy, Michigan, United States, 48098
      • Center for Digestive Health
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Missouri
    • Mexico, Missouri, United States, 65265
      • Center for Digestive and Liver Diseases
  • Montana
    • Bozeman, Montana, United States, 59718
      • Clinical Research Group of Montana, PLLC
  • New Jersey
    • Manalapan, New Jersey, United States, 07726
      • Marlboro Gastroenterology
  • New York
    • Bay Shore, New York, United States, 11706
      • Western Suffolk Gastroenterology Associates, LLP
    • Long Island City, New York, United States, 11021
      • Long Island Clinical Research Associates, LLP
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New Hyde Park, New York, United States, 11042
      • Digestive Medicine of Long Island
    • New York, New York, United States, 10128
      • Mount Sinai and Metropolitan Hospital
    • Troy, New York, United States, 12180
      • Upstate Gastroentrology Associates
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Peters Medical Research
    • Jacksonville, North Carolina, United States, 28546
      • East Carolina Gastroenterology
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Gastroenterology Associates
    • Cincinnati, Ohio, United States, 45219
      • Consultants For Clinical Research, Inc.
    • Cincinnati, Ohio, United States, 45220
      • Digestive Health Network
    • Cincinnati, Ohio, United States, 45242
      • Gastro Consultants of Greater Cincinnati
    • Dayton, Ohio, United States, 45415
      • Gild Consultants, P.C.
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Central Sooner Research
  • Pennsylvania
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Clinic
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • ClinSearch
    • Germantown, Tennessee, United States, 38138
      • Gastroenterology of Midsouth
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
  • Texas
    • Houston, Texas, United States, 77024
      • Houston Endoscopy & Research Center
    • San Antonio, Texas, United States, 78229
      • Gastroenterology Clinic of San Antonio
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Gastroenterology Associates of Tidewater
    • Christiansburg, Virginia, United States, 24073
      • New River Valley Research
  • Washington
    • Spokane, Washington, United States, 99204
      • Inland Empire Gastroenterology, P.S.
    • Spokane, Washington, United States, 99204
      • Spokane Digestive Disease Center, P.S.
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Waukesha, Wisconsin, United States, 53186
      • Aurora Health Center- Waukesha

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria - Acute Phase:

1. Male and female subjects aged at least 18 years with active mild to moderate UC may enter the Acute Phase of the study.
2. Must have a previous diagnosis of UC confirmed by histology and endoscopy or radiology.
3. Males or non-pregnant, non-lactating FOCP who have a negative serum pregnancy test prior to entering the study and who are using adequate forms of contraception for the duration of the study.
4. General medical assessment must be satisfactory and there must not be clinically significant and relevant abnormalities.
5. Subject must have had >2 acute episodes of UC (a documented episode of increased bowel frequency with rectal blood loss for which UC therapy was intensified) in their medical history.
6. Subjects who have relapsed on maintenance therapy after 2 weeks with doses of mesalamine at: a. <2.0g/day, will be allowed into the Acute Phase at 2.4g/day QD, or b. between 2.0g/day - 3.0g/day will be allowed into the Acute Phase at 4.8g/day QD.

Inclusion Criteria - Maintenance Phase:

1. Subjects determined to be quiescent at study entry on prior oral mesalamine therapy will be eligible to enter directly into the Maintenance Phase.
2. UC must have been considered to be quiescent, with scores of zero for both rectal bleeding and bowel movements.

Exclusion Criteria - Acute Phase:

1. Subjects who have been in relapse for >6 weeks.
2. Female subjects who are pregnant or lactating, including females with a positive pregnancy test at screening.
3. Subjects must not have used another investigational agent within the last 30 days prior to enrollment.
4. Subjects who have unsuccessfully treated their current relapse with steroids or a mesalamine dose of >2.0 g/day.
5. Subjects who have relapsed on maintenance therapy with doses of mesalamine >2.0g/day. If the subject had a recent dose reduction from 2.0g/day to less than or equal to 2.0g/day and relapsed within 2 weeks of that dose reduction, the subject will not be eligible.
6. Subjects who have used systemic or rectal steroids within the last 4 weeks prior to Baseline, immunosuppressants within the last 6 weeks, antibiotic use within the last 7 days or chronic use of any anti-inflammatory drugs within 7 days prior to Baseline.
7. Subjects with hypersensitivity to salicylates/aspirin are excluded.
8. Subjects with moderate or severe hepatic impairment.
9. Subjects with Crohn's Disease, proctitis (where the extent of inflammation is less than or equal to 15cm), short bowel syndrome, bleeding disorders, or active peptic ulcer disease.
10. Subjects with asthma are excluded only if they are known to be mesalamine-sensitive.
11. Subjects with a positive stool culture for enteric pathogens (including Salmonella, Shigella, Yersinia, Aeromonas, Plesiomonas or Campylobacter) are excluded, as are those with C. difficile toxin present or with ova or parasites as detected by microscopy.
12. Subjects who have a history of previous colonic surgery.
13. Subjects with moderate or severe renal impairment are contra-indicated for treatment with mesalamine compounds and are excluded from the study.
14. Subjects with current or recurrent disease that could affect the colon, the action, absorption or disposition of the study drug, or clinical or laboratory assessments.
15. Subjects with current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder that may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the study drug or procedures.
16. Subjects with a history of alcohol or other substance abuse within the previous year.
17. Subjects who withdrew from a mesalamine trial due to a possibly or probably related severe AE or SAE are not eligible to enter this study.

Exclusion Criteria - Maintenance Phase (in addition to above inclusion for the Acute Phase):

1. Subjects who have withdrawn from the Acute Phase before study visit A3.
2. Subjects with severe UC according to the PGA.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MMX Mesalamine	Drug: MMX Mesalamine; MMX™ mesalamine 2.4g/day to 4.8g/day once-daily (QD) (two to four 1.2g tablets MMX™ mesalamine, dosed QD,respectively).; Other Names: Lialda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months	Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Recurrence of UC During the Maintenance Phase at 12 Months	Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding.	12 Months
Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 6 Months	Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding. Compliance is a subject's adherence to a recommended course of treatment and for this study is calculated: [(Sum of days' supplies dispensed) divided by (Sum of days in all refill intervals)] x 100.	6 Months
Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 12 Months	Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding. Compliance is a subject's adherence to a recommended course of treatment and for this study is calculated: (Sum of days' supplies dispensed) divided by (Sum of days in all refill intervals) x 100.	12 months
Quiescent UC During the Maintenance Phase at 12 Months	Quiescent UC is defined as scores of 0 for both rectal bleeding and bowel movements. Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Bowel movements are assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).	12 Months
Endoscopic Remission of UC During the Maintenance Phase at 12 Months	Endoscopic remission is defined as an endoscopy score of less than or equal to 1. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal [intact vascular pattern; no friability or granulation], 1 = mild [erythema; decreased vascular pattern; minimal granularity], 2 = moderate [marked erythema; granularity; friability; absent vascular pattern; bleeding with minimal trauma; no ulcerations], 3 = severe [ulceration; spontaneous bleeding].	12 Months

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Kane S, Katz S, Jamal MM, Safdi M, Dolin B, Solomon D, Palmen M, Barrett K. Strategies in maintenance for patients receiving long-term therapy (SIMPLE): a study of MMX mesalamine for the long-term maintenance of quiescent ulcerative colitis. Inflamm Bowel Dis. 2012 Jun;18(6):1026-33. doi: 10.1002/ibd.21841. Epub 2011 Aug 11.
• Yarlas A, Yen L, Hodgkins P. The relationship among multiple patient-reported outcomes measures for patients with ulcerative colitis receiving treatment with MMX (R) formulated delayed-release mesalamine. Qual Life Res. 2015 Mar;24(3):671-83. doi: 10.1007/s11136-014-0797-2. Epub 2014 Sep 6.

Helpful Links

• FDA Recall Information
• FDA-approved label

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2007
• Primary Completion (Actual): August 17, 2009
• Study Completion (Actual): August 17, 2009

Study Registration Dates

• First Submitted: March 12, 2007
• First Submitted That Met QC Criteria: March 12, 2007
• First Posted (Estimate): March 13, 2007

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: compliance; clinical trial; oral; ulcerative colitis; maintenance; open label; clinical study; clinical research; mesalamine; long term; uc study; uc trial; uc research; once a day; once; daily; daily dosing; simple
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: SPD476-404