Safety and Efficacy of MMX Mesalamine/Mesalazine in Pediatric Subjects With Mild to Moderate Ulcerative Colitis

A Phase 3, Multicenter, Randomized, Double-blind Study to Determine the Safety and Efficacy of MMX Mesalamine/Mesalazine in Pediatric Subjects With Mild to Moderate Ulcerative Colitis, in Both Acute and Maintenance Phases

To assess clinical response to MMX mesalamine/mesalazine between a low and high dose in children and adolescents aged 5-17 years with mild to moderate Ulcerative Colitis (UC) or who are in remission.

Inclusion Criteria:

1. Ability to voluntarily provide written, signed, and dated (personally or via a legally authorized representative [LAR]) informed consent or assent as applicable to participate in the study.

2. Subject's parent/LAR demonstrates an understanding, ability, and willingness to fully comply with study procedures and restrictions.

3. Male and female children and adolescents aged 5-17 years, inclusive.

4. Body weight 18-90kg.

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

6. Diagnosed with mild to moderate UC, established by sigmoidoscopy or colonoscopy with compatible histology. Screened subjects may also have an unconfirmed diagnosis of mild to moderate UC; however the diagnosis of mild to moderate UC must have been established by sigmoidoscopy or colonoscopy with compatible histology prior to baseline visit.

7. Subject is able to swallow the investigational product whole.

   Double-blind Acute Phase:

8. Partial UC-DAI score ≥2 (a combined rectal bleeding and stool frequency score ≥1 and PGA=1 or 2) at the Baseline Visit, for which 5-ASA would be used as part of normal treatment.

9. If the subject is on 5-ASA treatment prior to study entry, then the dose must be stable. Stable therapy is defined as no change in dose, or no initiation of 5-ASA, from the onset of the current acute flare through discontinuation of therapy (required at the Baseline Visit).

   Double-blind Maintenance Phase:

10. Partial UC-DAI ≤1 (rectal bleeding=0, stool frequency ≤1, and PGA=0) at the Baseline Visit.

Exclusion Criteria:

1. Severe UC (defined by PGA=3).
2. Crohn's disease, bleeding disorders, active peptic ulcer disease, or UC known to be confined to the rectum (isolated rectal proctitis).
3. Asthma, only if known to be 5 ASA sensitive.
4. Positive stool culture for enteric pathogens (including Salmonella, Shigella, Yersinia, Aeromonas, Plesiomonas, or Campylobacter). Clostridium difficile toxin, ova, or parasites present.
5. Systemic or rectal corticosteroid use within 4 weeks prior to the Screening Visit. Topical, intranasal, or inhaled use is not exclusionary.
6. Immunomodulator (6-mercaptopurine, azathioprine) use within 6 weeks prior to the Screening Visit.
7. History of biologic (eg, anti-tumor necrosis factor agents, integrin receptor antagonists) use at any time.
8. Antibiotic use within 7 days prior to the Screening Visit.
9. Any anti-inflammatory drugs, not including 5-ASA treatment but including non-steroidal anti-inflammatory drugs such as aspirin, COX-2 inhibitors or ibuprofen, within 7 days prior to the Screening Visit unless used at over-the-counter levels for <3 days. However, prophylactic use of a stable dose of aspirin up to 325mg/day for cardiac disease is permitted.
10. Prebiotic/probiotic use within 7 days prior to the Screening Visit. Yogurt products are permitted.