Clinical trial NCT00446849: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ulcerative Colitis
Keywords: ulcerative colitis
compliance
mesalamine
clinical study
clinical trial
clinical research
maintenance
long term
uc study
uc trial
uc research
open label
once a day
once
daily
daily dosing
simple
oral
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2007-03-13
Enrollment: 290
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Clinical Recurrence of UC During the Maintenance Phase at 12 Months
timeFrame: 12 Months
measure: Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 6 Months
timeFrame: 6 Months
measure: Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 12 Months
timeFrame: 12 months
measure: Quiescent UC During the Maintenance Phase at 12 Months
timeFrame: 12 Months
measure: Endoscopic Remission of UC During the Maintenance Phase at 12 Months
timeFrame: 12 Months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Gastroenterology Assoc.
state: Alabama
city: Jonesboro
country: United States
facility: Clopton Clinic
state: Arkansas
city: Long Beach
country: United States
facility: VA Medical Center - Long Beach
state: California
city: San Diego
country: United States
facility: Sharp Rees-Stealy Medical Group
state: California
city: San Diego
country: United States
facility: Clinical Applications Laboratories, Inc.
state: California
city: Englewood
country: United States
facility: South Denver Gastroenterology, P.C.
state: Colorado
city: Greenwich
country: United States
facility: The Center for GI Medicine of Fairfield & Westchester, P.C.
state: Connecticut
city: Hamden
country: United States
facility: Medical Research Center of Connecticut, LLC
state: Connecticut
city: New Haven
country: United States
facility: Connecticut Gastroenterology Associates
state: Connecticut
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Clearwater
country: United States
facility: Advanced Digestive Care, PA
state: Florida
city: Hollywood
country: United States
facility: Southern Clinical Research Consultants
state: Florida
city: Jacksonville
country: United States
facility: Borland-Groover Clinic
state: Florida
city: New Smyrna Beach
country: United States
facility: United Medical Research
state: Florida
city: Palm Harbor
country: United States
facility: Advanced Gastroenterology Associates
state: Florida
city: Decatur
country: United States
facility: Soapstone Ctr. for Clin. Rsrch
state: Georgia
city: Macon
country: United States
facility: Gastroenterology Assoc./Cen.GA
state: Georgia
city: Marietta
country: United States
facility: NW GA Gastroenterology
state: Georgia
city: Moline
country: United States
facility: Midwest Clinical Research Associates
state: Illinois
city: Peoria
country: United States
facility: Accelovance
state: Illinois
city: Rockford
country: United States
facility: Rockford Gastroenterology Associates
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Hospital
state: Indiana
city: Davenport
country: United States
facility: Gastrointestinal Clinic of Quad Cities
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Overland Park
country: United States
facility: GI Associates
state: Kansas
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Annapolis
country: United States
facility: Digestive Disorders Associates Research Division
state: Maryland
city: Annapolis
country: United States
facility: Maryland Clinical Trials
state: Maryland
city: Laurel
country: United States
facility: Maryland Digestive Disease Research, LLC
state: Maryland
city: Troy
country: United States
facility: Center for Digestive Health
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Mexico
country: United States
facility: Center for Digestive and Liver Diseases
state: Missouri
city: Bozeman
country: United States
facility: Clinical Research Group of Montana, PLLC
state: Montana
city: Manalapan
country: United States
facility: Marlboro Gastroenterology
state: New Jersey
city: Bay Shore
country: United States
facility: Western Suffolk Gastroenterology Associates, LLP
state: New York
city: Long Island City
country: United States
facility: Long Island Clinical Research Associates, LLP
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Digestive Medicine of Long Island
state: New York
city: New York
country: United States
facility: Mount Sinai and Metropolitan Hospital
state: New York
city: Troy
country: United States
facility: Upstate Gastroentrology Associates
state: New York
city: High Point
country: United States
facility: Peters Medical Research
state: North Carolina
city: Jacksonville
country: United States
facility: East Carolina Gastroenterology
state: North Carolina
city: Beachwood
country: United States
facility: Gastroenterology Associates
state: Ohio
city: Cincinnati
country: United States
facility: Consultants for Clinical Research, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Digestive Health Network
state: Ohio
city: Cincinnati
country: United States
facility: Gastro Consultants of Greater Cincinnati
state: Ohio
city: Dayton
country: United States
facility: Gild Consultants, P.C.
state: Ohio
city: Norman
country: United States
facility: Central Sooner Research
state: Oklahoma
city: Sayre
country: United States
facility: Guthrie Clinic
state: Pennsylvania
city: Chattanooga
country: United States
facility: ClinSearch
state: Tennessee
city: Germantown
country: United States
facility: Gastroenterology of Midsouth
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Houston
country: United States
facility: Houston Endoscopy & Research Center
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Clinic of San Antonio
state: Texas
city: Chesapeake
country: United States
facility: Gastroenterology Associates of Tidewater
state: Virginia
city: Christiansburg
country: United States
facility: New River Valley Research
state: Virginia
city: Spokane
country: United States
facility: Inland Empire Gastroenterology, P.S.
state: Washington
city: Spokane
country: United States
facility: Spokane Digestive Disease Center, P.S.
state: Washington
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Sinai Medical Center
state: Wisconsin
city: Waukesha
country: United States
facility: Aurora Health Center- Waukesha
state: Wisconsin
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.