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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01124149
First received: May 13, 2010
Last updated: June 6, 2014
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Ulcerative Colitis
Drug: MMX mesalamine/ mesalazine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Percentage of Subjects in Complete Remission at Month 12 of Maintenance Phase [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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:
  • Percentage of Subjects in Clinical Remission at Month 12 of Maintenance Phase [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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 Phase [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • Percentage of Subjects With Mucosal Healing at 12 Months of Maintenance Phase [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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 Rectal Bleeding Score During the Acute Phase [ Time Frame: 3 and 8 weeks ] [ Designated as safety issue: No ]

    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).


  • Improvement in Stool Frequency Symptoms During the Acute Phase [ Time Frame: 3 and 8 weeks ] [ Designated as safety issue: No ]

    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 Complete Remission at Week 8 of Acute Phase [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]

    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 Phase [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    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).



Enrollment: 722
Study Start Date: June 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MMX mesalamine/ mesalazine 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
Other Name: Lialda, Mezavant, Mezavant XL, Mezavant LP

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01124149

  Show 105 Study Locations
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Geert R D'Haens, MD, PhD Imelda G.I. Clinical Research Centre
Principal Investigator: David Rubin, MD University of Chicago
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01124149     History of Changes
Other Study ID Numbers: SPD476-409, 2009-017044-13
Study First Received: May 13, 2010
Results First Received: September 30, 2013
Last Updated: June 6, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Ireland: Irish Medicines Board
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Institutional Review Board
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Romania: National Medicines Agency

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Colonic Diseases
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Pathologic Processes
Mesalamine
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014