Ability to Maintain or Achieve Clinical and Endoscopic Remission With MMX Mesalamine Once Daily in Adults With Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

A Phase 4, Open-label, Multicenter, Prospective Study to Evaluate the Effect of Remission Status on the Ability to Maintain or Achieve Clinical and Endoscopic Remission During a 12-Month, Long-term Maintenance Phase With 2.4g/Day MMX Mesalamine/Mesalazine Once Daily in Adult Subjects With Ulcerative Colitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01124149
• Other study ID #: SPD476-409
• Secondary ID: 2009-017044-13
• Status: Completed
• Phase: Phase 4
• Start date: June 29, 2010
• Est. completion date: December 7, 2012

Study information

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

Clinical Trial Summary

This study was designed to evaluate if subjects who achieve complete remission after 8 weeks of acute therapy with MMX mesalamine/mesalazine 4.8g/day given QD have better long-term outcomes and remain in remission longer compared with subjects who demonstrate only partial remission after acute therapy with MMX mesalamine/mesalazine 4.8g/day given QD. Therefore, subjects who achieve either complete or partial remission will enter into a 12-month maintenance phase, during which they will receive MMX mesalamine/mesalazine 2.4g/day given QD. Remission status for the 2 groups will be evaluated and compared at the end of this 12-month maintenance period. The data obtained from this study will provide scientifically meaningful information to demonstrate that achieving complete remission (clinical and endoscopic remission) is important for a better long-term prognosis, or that the current paradigm of symptomatic treatment is appropriate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 759
• Est. completion date: December 7, 2012
• Est. primary completion date: December 7, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adults aged 18 or older

2. Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol

3. Diagnosis of active mild to moderate UC (acute flare or newly diagnosed)

4. Stable maintenance therapy of 5-ASA less than or equal to 3.2 g/day (excluding MMX mesalamine/mesalazine), if 5-ASA is being taken at the onset of acute flare.

Exclusion Criteria:

1. Severe UC

2. Acute flare with onset greater than >6 weeks prior to baseline while on maintenance therapy. There is no limit to the onset of flare prior to baseline if the flare is untreated.

3. Acute flare while on maintenance MMX mesalamine/mesalazine (Lialda, Mezavant, Mezavant XL, Mezavant LP)

4. Unsuccessfully treated current acute flare using steroids or 5-ASA doses >3.2 g/day

5. Acute flare on a 5-ASA maintenance therapy of >3.2 g/day

6. Systemic or rectal steroids use within the 4 weeks prior to screening or immunosuppressants within the last 6 weeks prior to screening

7. History of biologic (anti-TNF agent) use

8. Antibiotic use or repeated use (>3 consecutive days of use at doses above the prescribed over-the-counter dose) of any anti-inflammatory drugs, including non-steroidal anti-inflammatory drugs such as aspirin, COX-2 inhibitors or ibuprofen, within 7 days prior to screening. However, prophylactic use of a stable dose of aspirin up to 325mg/day for cardiac disease is permitted

9. Current or recurrent disease, other than UC, that could affect the colon, the action, absorption, or disposition of the IMP, or clinical or laboratory assessments

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• MMX mesalamine/ mesalazine
4.8g/day given QD (four 1.2g tablets) for 8 weeks, 2.4g/day given QD (two 1.2g tablets) for 12 months

Locations

Country	Name	City	State
Belgium	Imelda General Hospital	Bonheiden
Belgium	vzw AZ Groeninge	Kortrijk
Belgium	Heilig Hart ziekenhuis vzw Roeselare-Menen	Roeselare
Canada	McMaster University Medical Centre	Hamilton	Ontario
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	CHAUQ- Hopital du Saint-Sacrement	Quebec
Canada	Alpha Recherche Clinique	Quebec City	Quebec
Canada	Toronto Digestive Disease Associates, Inc.	Toronto	Ontario
Colombia	Ugasend S.A.	Barranquilla	Atlantico
Colombia	FOQUS, Centro de Investigacion Clinica	Bogota	Cundinamarca
Colombia	Hospital pablo Tobon uribe	Medellin	Antioquia
Colombia	Promotora medica las Americas S.A.	Medellin	Antioquia
Czechia	Derma Plus s.r.o. Gastroenterology	Ceske Budejovice
Czechia	Private Gastroenterology centre	Ceske Budejovice
Czechia	Hepato-Gastroenterology HK s.r.o.	Hradec Kralove
Czechia	Nemocnice Jablonec nad Nisou	Jablonec nad Nisou
Czechia	Faculty hospital Plzen- Lochotin	Plzen
Czechia	IKEM (Institute klinicke a experimentalni mediciny)	Prague
Czechia	Klinicke Centrum ISCARE I.V.F.	Prague 7
Czechia	Nemocnice Tabor a.s.	Tabor
Czechia	Massarykova Nemocnice-Masaryk Hospital	Usti nad Labem
Czechia	Orlickoustecka nemocnice a.s. (Hospital)	Usti nad Orlici
France	Hopital Saint Andre	Bordeaux
France	CHU Estaing	Clermont-Ferrand
France	CHU Nantes- Hotel Dieu	Nantes
Germany	Medizinische Hochschule Hannover/ Zentrum Innere Medizin/Gastroenterologie	Hannover
Germany	Stawdtisches Klinikum Lueneburg Gastroenterologie	Lueneburg
Hungary	Debreceni Egyetem Orvos-es Egeszsegtudomanyi Centrum III. sz. Belgyogyazati Klinika	Debrecen
Hungary	Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza, Endoszkopos laboratorium	Gyula
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyrtrmi Oktato Korhaz, II. Belgyogyaszat	Miskolc
Hungary	Karolina Korhaz, Belgyogyaszat es Gasztroenterologia	Mosonmagyarovar
Hungary	Javorszky Odon Varosi Korhaz, Gasztroenterologia	Vac
India	Mehta Hospital	Ahmedabad	Gujarat
India	Institute of Digestive & Liver Diseases	Guwahati	Assam
India	Asian Institute of Gastroenterology	Hyderabad	Andhra Pradesh
India	Dr. Nijhawan Clinic	Jaipur	Rajasthan
India	S R Kalla Memorial Gastro & General Hospital	Jaipur	Rajasthan
India	Chhatrapati Shahuji Maharaj Medical University	Lucknow	UP
India	Dayanand Medical College and hospital	Ludhiana	Punjab
India	Kasturba Medical College Hospital	Mangalore	Kamataka
India	Gastroenterology & Endoscopy Centre	Nagpur	Maharashtra
India	Poona Hospital & Research Centre	Pune	Maharashtra
India	Sahyandri Speciality Hospital	Pune	Maharashtra
India	Sree Gokulam Medical College and Research Foundation	Thiruvananthapuram	Kerala
India	Manikya Institute of Gastroenterology & Hepatology	Visakhapatnam	Andhra Pradesh
Ireland	Adelaide and Meath Hospital	Dublin
Ireland	Beaumont Hospital	Dublin
Ireland	St Vincents' University Hospital	Dublin
Poland	NZOZ Centrum Medyczne Szpital Sw. Rodziny	Lodz
Poland	NZOZ Centrum Medyczne HCP	Poznan
Poland	Endoskopia Sp z o.o.	Sopot
Poland	Indyw. Spec. Prakt. Lek. w Dziedzinie Chirurgii Ogolnej i Gastroenterologii	Torun
Poland	Nzoz Vivamed	Warszawa
Poland	EMC Instytut Medyczny SA	Wroclaw
Poland	LexMedica	Wroclaw
Romania	Clinical Hospital "Dr. I. Cantacuzino"	Bucharest
Romania	Emergency University Clinical Hospital Bucuresti	Bucharest
Romania	Institutul Clinic Fundeni	Bucharest
Romania	CMI de Gastroenterologie	Targu Mures	Mures
Romania	Policlinic Algomed SRL	Timisoara
Romania	Policlinica "Dr. Citu" SRL	Timisoara
South Africa	Rose Park Hospital Boanerges CC Trials	Bloemfontein	Free State
South Africa	Kingsbury Hospital	Cape Town	Western Cape
South Africa	Louis Leipoldt Medical Centre	Cape Town	Western Cape
South Africa	Panorama Medi-Clinic	Cape Town	Western Cape
South Africa	Parklands Medical Centre	Durban	KwaZulu Natal
South Africa	St. Augustine's Hospital	Durban	KwaZulu- Natal
South Africa	Greenacres Hospital	Port Elizabeth
Spain	Hospital Universitario La Princesa	Madrid
United Kingdom	St Mark's Hospital	Harrow	Middlesex
United Kingdom	John Radcliffe Hospital	Headington	Oxfordshire
United States	Alexandria Clinical Research	Alexandria	Virginia
United States	Advanced Clinical Research Institute	Anaheim	California
United States	Digestive Disorders Associates	Annapolis	Maryland
United States	Atlanta Gastroenterology Associates, LLC	Atlanta	Georgia
United States	Digestive Disease Associates	Baltimore	Maryland
United States	Birmingham Gastroenterology Associates, PC	Birmingham	Alabama
United States	Conneticut Gastroenterolgy Institute	Bristol	Connecticut
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Ohio Gastroenterolgy and Liver Intstitute	Cincinnati	Ohio
United States	Gastrointestinal Clinic of Quad Cities	Davenport	Iowa
United States	Digestive & Liver Disease Specialists	Garden Grove	California
United States	Long Island Clinical Research Associates, LLP	Great Neck	New York
United States	LeBauer Research Associates	Greensboro	North Carolina
United States	S.D. Khan	Houston	Texas
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	Gastroenterology Associates, LLC	Kingsport	Tennessee
United States	Regional Gastroenterology Associates of Lancaster, Ltd.	Lancaster	Pennsylvania
United States	Long Beach VA Medical Center	Long Beach	California
United States	Atlanta Gastroenterology Associates	Marietta	Georgia
United States	New Orleans Research Institute	Metairie	Louisiana
United States	Center for Digestive & Liver Disease, Inc.	Mexico	Missouri
United States	Wisconsin Center for Advances Research	Milwaukee	Wisconsin
United States	Midwest Clinical Research Associates	Moline	Illinois
United States	Delta Research Partners	Monroe	Louisiana
United States	United Medical Research	New Smyrna Beach	Florida
United States	Advances Gastroenterology Associates	Palm Harbor	Florida
United States	Mayo Clinic	Rochester	Minnesota
United States	Gastroenterology Clinic of San Antonio, PA	San Antonio	Texas
United States	Clinical Applications Laboratories, Inc.	San Diego	California
United States	Colon and Rectal Disease Center	Sandy	Utah
United States	Physicians Research Option, LLC	Sandy	Utah
United States	Gastrointestinal Research Associates	Setauket	New York
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Center for Digestive Health	Troy	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Colombia,  Czechia,  France,  Germany,  Hungary,  India,  Ireland,  Poland,  Romania,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects in Complete Remission at Month 12 of Maintenance Phase	Complete remission was defined as a modified Ulcerative Colitis Disease Activity Index (UC-DAI) <=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. The modified UC-DAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is 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	Percentage of Subjects in Clinical Remission at Month 12 of Maintenance Phase	Clinical remission was defined as a score of 0 for rectal bleeding and stool frequency. Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is 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	Relapse in Ulcerative Colitis at Month 12 of Maintenance Phase	Relapse was defined in the Maintenance Phase as the need for alternative treatment for UC (including surgery); subjects were classified as having a relapse if they had withdrawn from the study due to a lack of efficacy.	12 months
Secondary	Percentage of Subjects With Mucosal Healing at 12 Months of Maintenance Phase	Subjects with mucosal healing were defined as subjects who had an endoscopy score <=1. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe).	12 months
Secondary	Improvement in Rectal Bleeding Score During the Acute Phase	Improvement was defined as at least a 1-point reduction in the rectal bleeding score from baseline at each assessment point. Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood).	3 and 8 weeks
Secondary	Improvement in Stool Frequency Symptoms During the Acute Phase	Improvement was defined as at least a 1-point reduction in the stool frequency score from baseline at each assessment point. Stool frequency is 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).	3 and 8 weeks
Secondary	Percentage of Subjects in Complete Remission at Week 8 of Acute Phase	Complete (clinical and endoscopic) remission was defined as a modified UC-DAI <=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. The modified UC-DAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is 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).	8 Weeks
Secondary	Percentage of Subjects in Partial Remission at Week 8 of Acute Phase	Partial remission was defined as a modified UC-DAI <=3 with a combined stool frequency and rectal bleeding score of <=1 and not in complete remission. The modified UC-DAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is 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).	8 weeks