Mesalamine 2 g Sachet for the Maintenance of Clinical and Endoscopic Remission in Ulcerative Colitis (UC)

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Investigating the Efficacy and Safety of Mesalamine 2 g Extended Release Granules (Sachet) for Maintenance of Clinical and Endoscopic Remission in Ulcerative Colitis

The purpose of this trial was to investigate the safety and efficacy of mesalamine 2 g extended release granules (sachet) once a day (QD) for maintenance of clinical and endoscopic remission in subjects with UC. The duration of treatment for each subject was 6 months.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Mesalamine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria
    • Multiprofile Hospital For Active Treatment Avis Medica
  • Plovdiv, Bulgaria
    • University Multiprofile Hospital for Active Treatment Kaspela
  • Sevlievo, Bulgaria
    • Medical Center Excelsior OOD
  • Sevlievo, Bulgaria
    • Medical Center-1-Sevlievo EOOD
  • Sofia, Bulgaria
    • City Clinic University Multiprofile Hospital for Active Treatment EOOD
  • Sofia, Bulgaria
    • Medical Center Asklepion - Humane Medicine Research EOOD
  • Sofia, Bulgaria
    • University Multiprofile Hospital for Active Treatment Sv Ivan Rilski EAD
  • Sofia, Bulgaria
    • University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna - ISUL EAD
  • Varna, Bulgaria
    • Diagnostic Consultative Centre Mladost M OOD
• Canada
  • Ontario
    • Ottawa, Ontario, Canada
      • Topstone Research Institute
  • Vaughan
    • Toronto, Vaughan, Canada
      • Toronto Digestive Disease Associates Inc
• Hungary
  • Budapest, Hungary
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Budapest, Hungary
    • Pannónia Magánorvosi Centrum Kft
  • Budapest, Hungary
    • Semmelweis Egyetem Institute
  • Debrecen, Hungary
    • Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft. Debreceni Egészségügyi Központja
  • Miskolc, Hungary
    • ENDOMEDIX Kft.
  • Mosonmagyarovar, Hungary
    • Karolina Korhaz Rendelointezet
  • Szekszard, Hungary
    • Clinfan Kft.
• Latvia
  • Daugavpils, Latvia
    • Polana-D, LTD
  • Riga, Latvia
    • Pauls Stradins Clinical University Hospital
  • Riga, Latvia
    • Riga East Clinical University Hospital
  • Riga, Latvia
    • Digestive Diseases Centre GASTRO
  • Riga, Latvia
    • Latvian Maritime Medicine Centre
• Mexico
  • Chihuahua, Mexico
    • ICARO Investigaciones en Medicina, S.A de C.V
  • Guadalajara, Mexico
    • Maria Auxiliadora Hospital
  • Zapopan, Mexico
    • Investigacion Biomedica para el Desarrollo de Farmacos, S.A. de C.V.
• Poland
  • Czestochowa, Poland
    • Niepubliczny Zaklad Opieki Zdrowotnej Intermed
  • Katowice, Poland
    • Economicus - NZOZ ALL-MEDICUS
  • Ksawerow, Poland
    • Investigational Site
  • Lodz, Poland
    • Niepubliczny Zaklad Opieki Zdrowotnej CENTRUM MEDYCZNE Szpital Swietej Rodziny
  • Lodz, Poland
    • SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
  • Sopot, Poland
    • ENDOSKOPIA Sp. z o.o.
  • Warsaw, Poland
    • Instytut Pomnik Centrum Zdrowia Dziecka
  • Dolnoslaskie
    • Sobótka, Dolnoslaskie, Poland
      • Osrodek Medycyny Rodzinnej Sp. z o.o.
    • Wroclaw, Dolnoslaskie, Poland
      • Lexmedica
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland
      • Zespół Przychodni Specjalistycznych PRIMA Sp. z o.o.
  • Podlaskie
    • Bialystok, Podlaskie, Poland
      • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Pomorskie
    • Gdansk, Pomorskie, Poland
      • Centrum Badań Klinicznych PI-House Sp. z o.o.
• Russian Federation
  • Krasnoyarsk, Russian Federation
    • Regional Clinical Hospital
  • Moscow, Russian Federation
    • City Clinical Hospital # 51
  • Nizhny Novgorod, Russian Federation
    • Nizhegorodskaya Regional Clinical Hospital n.a. Semashko
  • Novosibirsk, Russian Federation
    • Novosibirsk State Medical University
  • Novosibirsk, Russian Federation
    • Research Institute of Physiology of Sibirian Branch the RAMS
  • Omsk, Russian Federation
    • Omsk State Medical Academy
  • Rostov-on-Don, Russian Federation
    • Rostov State Medical University
  • Ryazan, Russian Federation
    • Ryazan Regional Clinical Hospital
  • Ryazan, Russian Federation
    • State Budget Institution of Ryazan region" Regional Clinical Hospital"
  • Saint Petersburg, Russian Federation
    • Russian Medical Military Academy n.a. S.M. Kirov
  • Saint Petersburg, Russian Federation
    • City Hospital #31
  • Samara, Russian Federation
    • Medical Company "Hepatolog", LLC
  • St. Petersburg, Russian Federation
    • City Polyclinic #38
  • Stavropol, Russian Federation
    • Stavropol State Medical Academy
• Serbia
  • Belgrade, Serbia
    • Clinical Hospital Center Bezanijska kosa
  • Belgrade, Serbia
    • Clinical Hospital Centar Zvezdara
  • Valjevo, Serbia
    • Health Center Valjevo
• Switzerland
  • Bern, Switzerland
    • Inselspital Bern
  • Bern, Switzerland
    • Investigational Site
  • Zürich, Switzerland
    • Universitätsspital Zürich
• Ukraine
  • Chernivtsi, Ukraine
    • Regional Municipal Institution Chernivtsi Regional Clinical Hospital
  • Dnipropetrovsk, Ukraine
    • Municipal Institution Dnipropetrovsk Regional Clinical Hospital n.a. I.I. Mechnykov
  • Kharkiv, Ukraine
    • Municipal Healthcare Institution Kharkiv City Clinical Hospital #2
  • Kharkiv, Ukraine
    • SI National Institute of Therapy n.a. L.T. Mala of National Academy of Medical Sciences of Ukraine
  • Kherson, Ukraine
    • Municipal Intitution "Kherson City Clinical Hospital n.a. A. and O. Tropinykh"
  • Kirovohrad, Ukraine
    • Private Enterprise Private Manufactire Company "Acinus"
  • Kremenchuk, Ukraine
    • Kremenchuk city Hospital # n.a O.T.Bohaievskyi
  • Kyiv, Ukraine
    • Kyiv City Clinical Hospital #8
  • Kyiv, Ukraine
    • Kyiv Municipal Clinical Hospital #18
  • Kyiv, Ukraine
    • Medical Center Universal Clinic Oberih of LLC Kapytal
  • Lviv, Ukraine
    • Municipal City Clinical emergency Hospital
  • Odesa, Ukraine
    • Municipal Institution Odesa Regional Clinical Hospital
  • Vinnytsia, Ukraine
    • Medical Clinical Research Center of Medical Center LLC Health Clinic
  • Vinnytsia, Ukraine
    • Vinnytsia Regional Clinical Hospital Hospital n.a. M.I. Pyrohov
  • Vinnytsya, Ukraine
    • Small Business Private Enterprise Medical Center "Pulse"
  • Zaporizhzhia, Ukraine
    • Municipal Institution 6th City Clinical Hospital of Zaporizhzhia City Council
  • Zaporizhzhia, Ukraine
    • Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
  • Zhytomyr, Ukraine
    • Medical Centre of PE First Private Clinic
  • Kyïv
    • Kyiv, Kyïv, Ukraine
      • Kyiv Municipal Clinical Hospital #18
    • Kyiv, Kyïv, Ukraine
      • Medical Center LLC Ukrainian German Antiulcer Gastroenterology Center BIK Kyiv
• United States
  • Arkansas
    • Little Rock, Arkansas, United States
      • Preferred Research Partners
  • California
    • Murrieta, California, United States
      • United Research Institute
  • Florida
    • Miami, Florida, United States
      • Research Associates of South Florida, LLC
    • Palmetto Bay, Florida, United States
      • IMIC
    • Pembroke Pines, Florida, United States
      • Medical Research Center of Florida
    • Sweetwater, Florida, United States
      • Lenus Research and Medical Group
  • Louisiana
    • Lake Charles, Louisiana, United States
      • Clinical Trials of SWLA, LLC
  • North Carolina
    • Fayetteville, North Carolina, United States
      • Cumberland Research Associates, LLC
    • Wilmington, North Carolina, United States
      • Wilmington Gastroenterology Associates
  • Tennessee
    • Hermitage, Tennessee, United States
      • Associates in Gastroenterology, PLC
    • Nashville, Tennessee, United States
      • Quality Medical Research, PLLC
  • Texas
    • Houston, Texas, United States
      • BI Research Center
    • Houston, Texas, United States
      • Biopharma Informatic Inc.
    • Pasadena, Texas, United States
      • Digestive Health Center
    • Tomball, Texas, United States
      • DM Clinical Research
  • Utah
    • Ogden, Utah, United States
      • Advanced Research Institute
  • Virginia
    • Christiansburg, Virginia, United States
      • New River Valley Research Institute
    • Norfolk, Virginia, United States
      • Digestive & Liver Disease Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects aged 18 to 75 years, with Ulcerative Colitis in remission

Exclusion Criteria:

• Evidence of other forms of inflammatory bowel disease
• Infectious disease (including human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV])
• Disease limited to proctitis <15 cm
• Short bowel syndrome
• Prior colon resection surgery
• History of severe/fulminant UC
• Intolerant or allergic to aspirin or salicylate derivatives
• Use of rectal formulations (5-aminosalicylic acid [5-ASA], steroids) within ≤7 days
• Women who are pregnant or nursing
• History of known malignancy
• History of bleeding disorders, active gastric or active duodenal ulcers, autoimmune diseases, or mental/ emotional disorders, that would interfere with their participation in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesalamine; Mesalamine 2 g extended release granules (sachet), administered orally once daily (QD) for 6 months.	Drug: Mesalamine; Pharmaceutical form: Granules in sachet; Route of administration: Oral use; Other Names: Pentasa; Mesalazine
Placebo Comparator: Placebo; Placebo matched to mesalamine extended release granules (sachet), administered orally QD for 6 months.	Drug: Placebo; Pharmaceutical form: Granules in sachet; Route of administration: Oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects With Remission at Month 6	The proportion of subjects with remission was defined by Clinical and Endoscopic Response Score: 0 for rectal bleeding; 0 or 1 for stool frequency; 0 or 1 for endoscopic score. The Clinical and Endoscopic Response Score ranged between 0 (normal) to 9 (severe disease), higher scores indicating greater disease severity. The score included clinical response component to assess subject's symptoms and endoscopic response component to assess objective evidence of inflammation. Clinical response component had two subscales: stool frequency ranging from 0 (normal number of stools) to 3 (>=5 stools more than normal) and rectal bleeding ranging from 0 (no blood seen) to 3 (blood alone passes). The Endoscopic response component had one subscale: flexible sigmoidoscopy/colonoscopy ranging from 0 (normal) to 3 (severe disease). Data is presented cumulative for all pathways.	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects in Clinical Remission at Month 2, 4, and 6	The proportion of subjects in clinical remission was defined as a score of 0 for rectal bleeding and 0 or 1 for stool frequency based on clinical response score component of the Clinical and Endoscopic Response Score. Clinical response score component had two subscales to assess subject's symptoms: rectal bleeding ranging from 0 (no blood seen) to 3 (blood alone passes) and stool frequency ranging from 0 (normal number of stools) to 3 (>=5 stools more than normal). The scores of clinical response component ranged from 0 (normal) to 6 (severe disease), higher scores indicating greater disease severity. Data is presented cumulative for all pathways.	Month 2, 4, and 6
Time to Relapse	Time to relapse was defined as the number of days from randomization to the day of withdrawal due to escalation of therapy. Data is presented cumulative for all pathways.	Time from randomization to the day of withdrawal due to escalation of therapy (up to 6 months)
Proportion of Subjects With an Increase From Baseline in the Clinical and Endoscopic Response Score by 2 or More Points in at Least 1 Component or by 1 or More Points in at Least 2 Components at Month 6	The proportion of subjects with an increase from baseline in the Clinical and Endoscopic Response Score by 2 or more points in at least 1 component, or by 1 or more points in at least 2 components were reported. The Clinical and Endoscopic Response Score ranged between 0 (normal) to 9 (severe disease), higher scores indicating greater disease severity. The score included clinical response component to assess subject's symptoms and endoscopic response component to assess objective evidence of inflammation. Clinical Response component had two subscales: stool frequency ranging from 0 (normal number of stools) to 3 (>=5 stools more than normal) and rectal bleeding ranging from 0 (no blood seen) to 3 (blood alone passes). The Endoscopic Response component had one subscale: flexible sigmoidoscopy/colonoscopy ranging from 0 (normal) to 3 (severe disease). Data is presented cumulative for all pathways.	Month 6
Change From Baseline in Serum C-reactive Protein (CRP) Levels at Month 2, 4, and 6	The adjusted mean change from baseline in serum CRP levels at Month 2, 4, and 6 were reported. Data is presented cumulative for all pathways.	Baseline, Month 2, 4, and 6
Change From Baseline in Fecal Calprotectin Levels at Month 2, 4, and 6	The adjusted mean change from baseline in fecal calprotectin levels at Month 2, 4, and 6 were reported. Data is presented cumulative for all pathways.	Baseline, Month 2, 4, and 6
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Scores at Months 2, 4, and 6	The IBDQ is an instrument used to assess quality of life in adult subjects with ulcerative colitis. It includes 32 questions on 4 domains of Health-Related Quality-of-Life (HRQOL): Bowel Systems (10 items), Emotional Function (12 items), Social Function (5 items), and Systemic Function (5 items). Subjects were asked to recall symptoms and quality of life from the last 2 weeks and rate each item on a 7-point Likert scale (1=worst to 7=best). The total IBDQ was computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better HRQOL. The adjusted mean change from baseline at Month 2, 4, and 6 for the IBDQ total scores were reported. Data is presented cumulative for all pathways.	Baseline, Month 2, 4, and 6
Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is defined as any untoward medical occurrence in a subject participating in a clinical trial. Any AEs includes serious as well as non-serious AEs. An SAE is defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect, or was an important medical event. Any AE which occurred in the time interval from initial dosing (investigational medicinal product [IMP] intake) to the end of treatment visit (Month 6) was considered treatment-emergent. Data is presented cumulative for all pathways.	Up to Month 6
Severity of Adverse Events	The number of subjects with intensity of AEs (classified as mild, moderate or severe) were presented. Data is presented cumulative for all pathways.	Up to Month 6
Proportion of Subjects With Markedly Abnormal Laboratory Values: Hematology	Proportion of subjects with markedly abnormal changes from baseline in hematology values are presented. Criteria for markedly abnormal laboratory (Hematology): Basophils/Leukocytes: >=5%, Eosinophils/Leukocytes: >=10%, Erythrocytes: <=3.5*10^6/μL, Hematocrit: <=0.32%; >=0.56%, Hemoglobin: <=11.5 g/dL, Leukocytes: <=2.8*10^3/μL; >=16.0*10^3/μL, Lymphocytes/Leukocytes: <=10%; >=80%, Monocytes/Leukocytes: >=20%, Neutrophils/Leukocytes: <=15%; >=90%, Platelets: <=75*10^3/μL; >=700*10^3/μL. Data is presented cumulative for all pathways.	Baseline, Month 6
Proportion of Subjects With Markedly Abnormal Laboratory Values: Coagulation	Proportion of subjects with markedly abnormal changes from baseline in coagulation values are presented. Criteria for markedly abnormal laboratory (coagulation): Activated Partial Thromboplastin Time (aPTT): >70 seconds (sec), Prothrombin International Normalized Ratio (INR): <0.8; >1.1. Data is presented cumulative for all pathways.	Baseline, Month 6
Proportion of Subjects With Markedly Abnormal Laboratory Values: Serum Chemistry	Proportion of subjects with markedly abnormal changes from baseline in serum chemistry values are presented. Criteria for markedly abnormal laboratory (serum chemistry): Alanine Aminotransferase (ALT): >3*upper limit of normal (ULN), Alkaline Phosphatase (ALP): >3*ULN and 25% increase (inc) from baseline (BL), Aspartate Aminotransferase (AST): >3* ULN, Bilirubin: >=1.5* ULN, Blood Urea Nitrogen: >=10.7 mg/dL, Calcium: <=1.8 mg/dL; >=3.9 mg/dL, Chloride: <=90 mmol/L; >=115 mmol/L, Creatinine: >=177 mg/dL, Gamma Glutamyl Transferase: >3*ULN, Glomerular Filtration Rate (GFR): <30 mL/min, Glucose: <=2.8 mg/dL; >=10 mg/dL, Potassium: <=3.0 mmol/L; >=5.8 mmol/L, Sodium: <=130 mmol/L; >=155 mmol/L. Data is presented cumulative for all pathways.	Baseline, Month 6

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): September 19, 2018
• Study Completion (Actual): September 19, 2018

Study Registration Dates

• First Submitted: August 12, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Actual): November 8, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: 000175; 2015-002558-11 (EudraCT Number)