MedPath

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

Phase 4
Completed
Conditions
Ulcerative Colitis
Interventions
Registration Number
NCT01124149
Lead Sponsor
Shire
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
759
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
MMX mesalamine/ mesalazineMMX mesalamine/ mesalazine-
Primary Outcome Measures
NameTimeMethod
Percentage of Subjects in Complete Remission at Month 12 of Maintenance Phase12 months

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).

Secondary Outcome Measures
NameTimeMethod
Percentage of Subjects With Mucosal Healing at 12 Months of Maintenance Phase12 months

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).

Improvement in Stool Frequency Symptoms During the Acute Phase3 and 8 weeks

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).

Percentage of Subjects in Clinical Remission at Month 12 of Maintenance Phase12 months

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).

Relapse in Ulcerative Colitis at Month 12 of Maintenance Phase12 months

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.

Improvement in Rectal Bleeding Score During the Acute Phase3 and 8 weeks

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).

Percentage of Subjects in Complete Remission at Week 8 of Acute Phase8 Weeks

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).

Percentage of Subjects in Partial Remission at Week 8 of Acute Phase8 weeks

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).

Trial Locations

Locations (105)

Advanced Clinical Research Institute

🇺🇸

Anaheim, California, United States

Digestive Disorders Associates

🇺🇸

Annapolis, Maryland, United States

University of Chicago Medical Center

🇺🇸

Chicago, Illinois, United States

Clinical Applications Laboratories, Inc.

🇺🇸

San Diego, California, United States

Atlanta Gastroenterology Associates

🇺🇸

Marietta, Georgia, United States

Advances Gastroenterology Associates

🇺🇸

Palm Harbor, Florida, United States

vzw AZ Groeninge

🇧🇪

Kortrijk, Belgium

IKEM (Institute klinicke a experimentalni mediciny)

🇨🇿

Prague, Czechia

Imelda General Hospital

🇧🇪

Bonheiden, Belgium

Heilig Hart ziekenhuis vzw Roeselare-Menen

🇧🇪

Roeselare, Belgium

Promotora medica las Americas S.A.

🇨🇴

Medellin, Antioquia, Colombia

Manikya Institute of Gastroenterology & Hepatology

🇮🇳

Visakhapatnam, Andhra Pradesh, India

McMaster University Medical Centre

🇨🇦

Hamilton, Ontario, Canada

Sahyandri Speciality Hospital

🇮🇳

Pune, Maharashtra, India

Mehta Hospital

🇮🇳

Ahmedabad, Gujarat, India

Gastroenterology & Endoscopy Centre

🇮🇳

Nagpur, Maharashtra, India

S R Kalla Memorial Gastro & General Hospital

🇮🇳

Jaipur, Rajasthan, India

Royal Victoria Hospital

🇨🇦

Montreal, Quebec, Canada

Gastrointestinal Research Associates

🇺🇸

Setauket, New York, United States

Ugasend S.A.

🇨🇴

Barranquilla, Atlantico, Colombia

Asian Institute of Gastroenterology

🇮🇳

Hyderabad, Andhra Pradesh, India

CHU Estaing

🇫🇷

Clermont-Ferrand, France

Alpha Recherche Clinique

🇨🇦

Quebec City, Quebec, Canada

Institute of Digestive & Liver Diseases

🇮🇳

Guwahati, Assam, India

Sree Gokulam Medical College and Research Foundation

🇮🇳

Thiruvananthapuram, Kerala, India

Kasturba Medical College Hospital

🇮🇳

Mangalore, Kamataka, India

St Vincents' University Hospital

🇮🇪

Dublin, Ireland

CMI de Gastroenterologie

🇷🇴

Targu Mures, Mures, Romania

Parklands Medical Centre

🇿🇦

Durban, KwaZulu Natal, South Africa

EMC Instytut Medyczny SA

🇵🇱

Wroclaw, Poland

Clinical Hospital "Dr. I. Cantacuzino"

🇷🇴

Bucharest, Romania

Hospital Universitario La Princesa

🇪🇸

Madrid, Spain

Rose Park Hospital Boanerges CC Trials

🇿🇦

Bloemfontein, Free State, South Africa

Dr. Nijhawan Clinic

🇮🇳

Jaipur, Rajasthan, India

Greenacres Hospital

🇿🇦

Port Elizabeth, South Africa

Beaumont Hospital

🇮🇪

Dublin, Ireland

NZOZ Centrum Medyczne HCP

🇵🇱

Poznan, Poland

Nzoz Vivamed

🇵🇱

Warszawa, Poland

Emergency University Clinical Hospital Bucuresti

🇷🇴

Bucharest, Romania

St. Augustine's Hospital

🇿🇦

Durban, KwaZulu- Natal, South Africa

Hospital pablo Tobon uribe

🇨🇴

Medellin, Antioquia, Colombia

Javorszky Odon Varosi Korhaz, Gasztroenterologia

🇭🇺

Vac, Hungary

Panorama Medi-Clinic

🇿🇦

Cape Town, Western Cape, South Africa

Borsod-Abauj-Zemplen Megyei Korhaz es Egyrtrmi Oktato Korhaz, II. Belgyogyaszat

🇭🇺

Miskolc, Hungary

Adelaide and Meath Hospital

🇮🇪

Dublin, Ireland

Policlinic Algomed SRL

🇷🇴

Timisoara, Romania

Dayanand Medical College and hospital

🇮🇳

Ludhiana, Punjab, India

LexMedica

🇵🇱

Wroclaw, Poland

Debreceni Egyetem Orvos-es Egeszsegtudomanyi Centrum III. sz. Belgyogyazati Klinika

🇭🇺

Debrecen, Hungary

Endoskopia Sp z o.o.

🇵🇱

Sopot, Poland

Institutul Clinic Fundeni

🇷🇴

Bucharest, Romania

Poona Hospital & Research Centre

🇮🇳

Pune, Maharashtra, India

John Radcliffe Hospital

🇬🇧

Headington, Oxfordshire, United Kingdom

Birmingham Gastroenterology Associates, PC

🇺🇸

Birmingham, Alabama, United States

Toronto Digestive Disease Associates, Inc.

🇨🇦

Toronto, Ontario, Canada

CHAUQ- Hopital du Saint-Sacrement

🇨🇦

Quebec, Canada

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Long Beach VA Medical Center

🇺🇸

Long Beach, California, United States

Digestive & Liver Disease Specialists

🇺🇸

Garden Grove, California, United States

Borland-Groover Clinic

🇺🇸

Jacksonville, Florida, United States

Conneticut Gastroenterolgy Institute

🇺🇸

Bristol, Connecticut, United States

United Medical Research

🇺🇸

New Smyrna Beach, Florida, United States

Atlanta Gastroenterology Associates, LLC

🇺🇸

Atlanta, Georgia, United States

Gastrointestinal Clinic of Quad Cities

🇺🇸

Davenport, Iowa, United States

Midwest Clinical Research Associates

🇺🇸

Moline, Illinois, United States

Delta Research Partners

🇺🇸

Monroe, Louisiana, United States

New Orleans Research Institute

🇺🇸

Metairie, Louisiana, United States

Louisiana Research Center, LLC

🇺🇸

Shreveport, Louisiana, United States

Digestive Disease Associates

🇺🇸

Baltimore, Maryland, United States

Center for Digestive Health

🇺🇸

Troy, Michigan, United States

Center for Digestive & Liver Disease, Inc.

🇺🇸

Mexico, Missouri, United States

Long Island Clinical Research Associates, LLP

🇺🇸

Great Neck, New York, United States

LeBauer Research Associates

🇺🇸

Greensboro, North Carolina, United States

Ohio Gastroenterolgy and Liver Intstitute

🇺🇸

Cincinnati, Ohio, United States

Gastroenterology Associates, LLC

🇺🇸

Kingsport, Tennessee, United States

Regional Gastroenterology Associates of Lancaster, Ltd.

🇺🇸

Lancaster, Pennsylvania, United States

S.D. Khan

🇺🇸

Houston, Texas, United States

Gastroenterology Clinic of San Antonio, PA

🇺🇸

San Antonio, Texas, United States

Colon and Rectal Disease Center

🇺🇸

Sandy, Utah, United States

Physicians Research Option, LLC

🇺🇸

Sandy, Utah, United States

Wisconsin Center for Advances Research

🇺🇸

Milwaukee, Wisconsin, United States

FOQUS, Centro de Investigacion Clinica

🇨🇴

Bogota, Cundinamarca, Colombia

Private Gastroenterology centre

🇨🇿

Ceske Budejovice, Czechia

Derma Plus s.r.o. Gastroenterology

🇨🇿

Ceske Budejovice, Czechia

Hepato-Gastroenterology HK s.r.o.

🇨🇿

Hradec Kralove, Czechia

Nemocnice Jablonec nad Nisou

🇨🇿

Jablonec nad Nisou, Czechia

Klinicke Centrum ISCARE I.V.F.

🇨🇿

Prague 7, Czechia

Faculty hospital Plzen- Lochotin

🇨🇿

Plzen, Czechia

Massarykova Nemocnice-Masaryk Hospital

🇨🇿

Usti nad Labem, Czechia

Orlickoustecka nemocnice a.s. (Hospital)

🇨🇿

Usti nad Orlici, Czechia

Nemocnice Tabor a.s.

🇨🇿

Tabor, Czechia

Hopital Saint Andre

🇫🇷

Bordeaux, France

CHU Nantes- Hotel Dieu

🇫🇷

Nantes, France

Medizinische Hochschule Hannover/ Zentrum Innere Medizin/Gastroenterologie

🇩🇪

Hannover, Germany

Stawdtisches Klinikum Lueneburg Gastroenterologie

🇩🇪

Lueneburg, Germany

Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza, Endoszkopos laboratorium

🇭🇺

Gyula, Hungary

Karolina Korhaz, Belgyogyaszat es Gasztroenterologia

🇭🇺

Mosonmagyarovar, Hungary

Chhatrapati Shahuji Maharaj Medical University

🇮🇳

Lucknow, UP, India

NZOZ Centrum Medyczne Szpital Sw. Rodziny

🇵🇱

Lodz, Poland

Indyw. Spec. Prakt. Lek. w Dziedzinie Chirurgii Ogolnej i Gastroenterologii

🇵🇱

Torun, Poland

Policlinica "Dr. Citu" SRL

🇷🇴

Timisoara, Romania

Louis Leipoldt Medical Centre

🇿🇦

Cape Town, Western Cape, South Africa

Kingsbury Hospital

🇿🇦

Cape Town, Western Cape, South Africa

St Mark's Hospital

🇬🇧

Harrow, Middlesex, United Kingdom

Alexandria Clinical Research

🇺🇸

Alexandria, Virginia, United States

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