Safety and Efficacy of MMX Mesalamine/Mesalazine in Pediatric Subjects With Mild to Moderate Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Drug: MMX Mesalamine/Mesalazine (Low Dose)Drug: MMX Mesalamine/Mesalazine (High Dose)
- Registration Number
- NCT02093663
- Lead Sponsor
- Shire
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 107
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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.
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Subject's parent/LAR demonstrates an understanding, ability, and willingness to fully comply with study procedures and restrictions.
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Male and female children and adolescents aged 5-17 years, inclusive.
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Body weight 18-90kg.
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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.
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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.
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Subject is able to swallow the investigational product whole.
Double-blind Acute Phase:
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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.
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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:
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Partial UC-DAI ≤1 (rectal bleeding=0, stool frequency ≤1, and PGA=0) at the Baseline Visit.
- Severe UC (defined by PGA=3).
- Crohn's disease, bleeding disorders, active peptic ulcer disease, or UC known to be confined to the rectum (isolated rectal proctitis).
- Asthma, only if known to be 5 ASA sensitive.
- Positive stool culture for enteric pathogens (including Salmonella, Shigella, Yersinia, Aeromonas, Plesiomonas, or Campylobacter). Clostridium difficile toxin, ova, or parasites present.
- Systemic or rectal corticosteroid use within 4 weeks prior to the Screening Visit. Topical, intranasal, or inhaled use is not exclusionary.
- Immunomodulator (6-mercaptopurine, azathioprine) use within 6 weeks prior to the Screening Visit.
- History of biologic (eg, anti-tumor necrosis factor agents, integrin receptor antagonists) use at any time.
- Antibiotic use within 7 days prior to the Screening Visit.
- 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.
- Prebiotic/probiotic use within 7 days prior to the Screening Visit. Yogurt products are permitted.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MMX Mesalamine/Mesalazine (Low Dose) MMX Mesalamine/Mesalazine (Low Dose) Once daily, tablets - the amount depends on the participants weight; 900 milligram per day (mg/day) for participants weighing 18 kg to less than or equal to (\<=) 23 kilograms (kg); 1200 mg/day for participants weighing greater than (\>) 23 kg to \<= 35 kg; 1800 mg/day for participants weighing \> 35 kg to \<= 50 kg; 2400 mg/day for participants weighing \> 50 kg to \<= 90 kg. MMX Mesalamine/Mesalazine (High Dose) MMX Mesalamine/Mesalazine (High Dose) Once daily, tablets - the amount depends on the participants weight;1800 mg/day for participants weighing 18 kg to \<= 23 kg; 2400 mg/day for participants weighing \> 23 kg to \<= 35 kg; 3600 mg/day for participants weighing \> 35 kg to \<= 50 kg; 4800 mg/day for participants weighing \> 50 kg to \<= 90 kg.
- Primary Outcome Measures
Name Time Method Number of Participants With Clinical Response During Double-Blind Acute Phase at Week 8 Week 8 Clinical response was defined as partial ulcerative colitis disease activity index (UC-DAI) score \< or =1 with rectal bleeding = 0, stool frequency \< or =1, and physician's global assessment (PGA = 0). Number of participants with clinical response were reported.
Number of Participants With Clinical Response During Double-blind Maintenance Phase at Week 26 Week 26 Clinical response was defined as partial UC-DAI \<=1 with (rectal bleeding = 0, stool frequency \< or =1, and PGA = 0). Number of participants who had maintained clinical response were reported.
- Secondary Outcome Measures
Name Time Method Number of Participants With Clinical and Endoscopic Response During Double Blind Acute Phase at Week 8 Using Central Reading Week 8 Clinical and endoscopic response was defined as UC-DAI \<=2 with rectal bleeding = 0 and stool frequency \<=1, and PGA = 0, and with mucosal healing (endoscopy score \<=1) at least a 1 point reduction in endoscopy score from baseline based on central reading. Participants with missing data at week 8 were assumed not to had a clinical response. Participants who completed week 8 but did not have central reading endoscopies at both baseline and week 8 were excluded. Number of participants with clinical and endoscopic response were reported.
Number of Participants With Remission at Pediatric Ulcerative Colitis Activity Index (PUCAI) Score During Double-Blind Maintenance Phase at Week 26 Week 26 PUCAI was a physician-administered measure that focuses on 6 key signs and symptoms of UC and activity limitations producing a total score ranging from 0-85 with higher scores being worse. Recommended cut-off scores to differentiate disease activity are \< 10 (remission); 11-30 (mild); 31-64 (moderate) and \> 65 (severe). Number of participants with remission at PUCAI score during double-blind maintenance phase at week 26 were reported.
Number of Participants With Clinical and Endoscopic Response During Double-Blind Maintenance Phase at Week 26 Using Local Reading Week 26 Clinical and endoscopic response was defined as UC-DAI \< or = 2 with rectal bleeding=0, stool frequency \< or = 1, PGA=0, and with mucosal healing (endoscopy score \< or = 1) based on local reading. Number of participants who had maintained clinical and endoscopic response during double-blind maintenance phase at week 26 using local reading were reported.
Number of Participants With Improvement in Pediatric Ulcerative Colitis Activity Index (PUCAI) Score During Double-blind Acute Phase at Week 8 Week 8 PUCAI was a physician-administered measure that focuses on 6 key signs and symptoms of UC and activity limitations producing a total score ranging from 0-85 with higher scores being worse. Recommended cut-off scores to differentiate disease activity are \< 10 (remission); 11-30 (mild); 31-64 (moderate) and \> 65 (severe). Participants with an improvement (change of greater than or equal to \[\> or =\] 20 points) in PUCAI score. Number of participants with improvement in PUCAI score during Double-blind Acute Phase at Week 8 were reported.
Number of Participants With Clinical and Endoscopic Response During Double-Blind Maintenance Phase at Week 26 Using Central Reading Week 26 Clinical and endoscopic response was defined as UC-DAI \< or =2 with rectal bleeding=0, stool frequency \< or =1, PGA=0, and with mucosal healing (endoscopy score \< or =1) based on central reading at Week 26. Number of participants with clinical and endoscopic response during double-blind maintenance phase at Week 26 using central reading were reported.
Number of Participants With Clinical and Endoscopic Response During Double Blind Acute Phase at Week 8 Using Local Reading Week 8 Clinical and endoscopic response was defined as UC-DAI \< or =2 with rectal bleeding = 0 and stool frequency \< or =1, and PGA = 0, and with mucosal healing (endoscopy score \< or =1) at least a 1 point reduction in endoscopy score from baseline based on local reading. Participants with missing data at week 8 were assumed not to had a clinical response. Participants who completed week 8 but did not have local reading endoscopies at both baseline and week 8 were excluded. Number of participants with clinical and endoscopic response were reported.
Change From Baseline in Daily Ulcerative Colitis Scale (DUCS) Score During Double-Blind Acute Phase Baseline to Week 8 DUCS score was to measure 7 specific signs or symptom and one impact (abdominal pain, nocturnal stool, daytime stool, blood in stool, diarrhea, urgency, tiredness) of UC with each item score ranged from 0 (worst) to 10 (best) with the overall score ranged from 0 (worst) to 70 (best) based on the responses. Change in the DUCS score from baseline to Week 8 during DBA phase were reported.
Change From Baseline in Daily Ulcerative Colitis Scale (DUCS) Score During Double-Blind Maintenance Phase Baseline, Week 13, and Week 26 DUCS score was to measure 7 specific signs or symptom and one impact (abdominal pain, nocturnal stool, daytime stool, blood in stool, diarrhea, urgency, tiredness) of UC with each score range from 0 (worst) to 10 (best) with the overall score ranging from 0 (worst) to 70 (best) based on the responses. Change from Baseline in DUCS score during double-blind maintenance phase at week 13 and Week 26 wwere reported.
Trial Locations
- Locations (33)
University of Maryland Children's Hospital
🇺🇸Baltimore, Maryland, United States
John Hopkins
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Minnesota Children's Hospital
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic Gastroenterology
🇺🇸Rochester, Minnesota, United States
Texas Digestive Disease Consultants
🇺🇸Southlake, Texas, United States
Klinika Gastroenterologii I Pediatrii
🇵🇱Lodz, Poland
Klinika Pediatrii Gastroenterologii I Zywienia
🇵🇱Krakow, Poland
Wojewodzki Specjalistyczny Szpital Dzieciecy
🇵🇱Olsztyn, Poland
Gabinet Lekarski-Bartosz Korczowski
🇵🇱Rzeszow, Poland
Detská fakultná nemocnica s poliklinikou
🇸🇰Banska Bystrica, Slovakia
King's College Hospital
🇬🇧London, United Kingdom
Univerzitna Nemocnica Martin
🇸🇰Martin, Slovakia
Barts Health NHS Trust, Royal London Hospital
🇬🇧London, United Kingdom
Newton Wellesley Hospital
🇺🇸Newton, Massachusetts, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Carilion Medical Center
🇺🇸Roanoke, Virginia, United States
Baz Megyei Korhaz Es Egyetemi Oktatokorhaz
🇭🇺Miskolc, Hungary
Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktato Korhaz
🇭🇺Nyiregyhaza, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺Szeged, Hungary
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Schneider Medical Centre
🇮🇱Petach Tikva, Israel
Rambam Health Corporation
🇮🇱Haifa, Israel
Soroka Medical Center
🇮🇱Be'er Sheva, Israel
University Children's Hospital
🇸🇰Bratislava, Slovakia
Great Ormond Street Hospital
🇬🇧London, United Kingdom
University of Alberta Pediatric Gastroenterology & Nutrition
🇨🇦Edmonton, Alberta, Canada
Szent Janos Korhaz És Észak-budai Egyesitett Korha
🇭🇺Budapest, Hungary
Bekes Megyei Pandy Kalman Korhaz
🇭🇺Gyula, Hungary
Alder Hey Children's Hospital
🇬🇧Liverpool, United Kingdom
Oddzial Gastroenterologii I Hepatologii
🇵🇱Warszawa, Poland
Uniwersytecki Dzieciecy Szpital Kliniczny im. Ludwika Zamenhofa
🇵🇱Bialystok, Poland
Uniwersytecki Szpital Kliniczny We Wrocławiu
🇵🇱Wrocław, Poland