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)

Ulcerative Colitis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00446849
• Other study ID #: SPD476-404
• Status: Completed
• Phase: Phase 4
• Start date: May 1, 2007
• Est. completion date: August 17, 2009

Study information

• Verified date: June 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 290
• Est. completion date: August 17, 2009
• Est. primary completion date: August 17, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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).

Locations

Country	Name	City	State
United States	Digestive Disorders Associates Research Division	Annapolis	Maryland
United States	Maryland Clinical Trials	Annapolis	Maryland
United States	Western Suffolk Gastroenterology Associates, LLP	Bay Shore	New York
United States	Gastroenterology Associates	Beachwood	Ohio
United States	Birmingham Gastroenterology Assoc.	Birmingham	Alabama
United States	Clinical Research Group of Montana, PLLC	Bozeman	Montana
United States	ClinSearch	Chattanooga	Tennessee
United States	Gastroenterology Associates of Tidewater	Chesapeake	Virginia
United States	New River Valley Research	Christiansburg	Virginia
United States	Consultants for Clinical Research, Inc.	Cincinnati	Ohio
United States	Digestive Health Network	Cincinnati	Ohio
United States	Gastro Consultants of Greater Cincinnati	Cincinnati	Ohio
United States	Advanced Digestive Care, PA	Clearwater	Florida
United States	Gastrointestinal Clinic of Quad Cities	Davenport	Iowa
United States	Gild Consultants, P.C.	Dayton	Ohio
United States	Soapstone Ctr. for Clin. Rsrch	Decatur	Georgia
United States	South Denver Gastroenterology, P.C.	Englewood	Colorado
United States	Gastroenterology of Midsouth	Germantown	Tennessee
United States	The Center for GI Medicine of Fairfield & Westchester, P.C.	Greenwich	Connecticut
United States	Medical Research Center of Connecticut, LLC	Hamden	Connecticut
United States	Peters Medical Research	High Point	North Carolina
United States	Southern Clinical Research Consultants	Hollywood	Florida
United States	Houston Endoscopy & Research Center	Houston	Texas
United States	Indiana University Hospital	Indianapolis	Indiana
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	East Carolina Gastroenterology	Jacksonville	North Carolina
United States	Clopton Clinic	Jonesboro	Arkansas
United States	Holston Medical Group	Kingsport	Tennessee
United States	Maryland Digestive Disease Research, LLC	Laurel	Maryland
United States	VA Medical Center - Long Beach	Long Beach	California
United States	Long Island Clinical Research Associates, LLP	Long Island City	New York
United States	Gastroenterology Assoc./Cen.GA	Macon	Georgia
United States	Marlboro Gastroenterology	Manalapan	New Jersey
United States	North Shore University Hospital	Manhasset	New York
United States	NW GA Gastroenterology	Marietta	Georgia
United States	Center for Digestive and Liver Diseases	Mexico	Missouri
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Midwest Clinical Research Associates	Moline	Illinois
United States	Connecticut Gastroenterology Associates	New Haven	Connecticut
United States	Digestive Medicine of Long Island	New Hyde Park	New York
United States	United Medical Research	New Smyrna Beach	Florida
United States	Mount Sinai and Metropolitan Hospital	New York	New York
United States	Central Sooner Research	Norman	Oklahoma
United States	GI Associates	Overland Park	Kansas
United States	Advanced Gastroenterology Associates	Palm Harbor	Florida
United States	Accelovance	Peoria	Illinois
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Rockford Gastroenterology Associates	Rockford	Illinois
United States	Gastroenterology Clinic of San Antonio	San Antonio	Texas
United States	Clinical Applications Laboratories, Inc.	San Diego	California
United States	Sharp Rees-Stealy Medical Group	San Diego	California
United States	Guthrie Clinic	Sayre	Pennsylvania
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Inland Empire Gastroenterology, P.S.	Spokane	Washington
United States	Spokane Digestive Disease Center, P.S.	Spokane	Washington
United States	Center for Digestive Health	Troy	Michigan
United States	Upstate Gastroentrology Associates	Troy	New York
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Aurora Health Center- Waukesha	Waukesha	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   FDA recall information
•   FDA-approved label