Mesalamine 4 g Sachet for the Induction of Remission in Active, Mild to Moderate Ulcerative Colitis (UC)

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Investigating the Efficacy and Safety of Mesalamine 4 g Extended Release Granules (Sachet) for the Induction of Clinical and Endoscopic Remission in Active, Mild to Moderate Ulcerative Colitis

The purpose of this trial is to investigate the efficacy of mesalamine for the induction of clinical and endoscopic remission in subjects with active, mild to moderate UC. Subject will receive 4 g extended release granules (sachet) once daily.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 228
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria
    • Multiprofile Hospital For Active Treatment Avis Medica
  • 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
  • Vaughan, Canada
    • Toronto Digestive Disease Associates
  • Ontario
    • Ottawa, Ontario, Canada
      • Topstone Research Institute
• 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
    • Investigación 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
    • Investigational Site
  • Warsaw, Poland
    • Centrum Zdrowia Matki, Dziecka i Mlodziezy
  • 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 Badan 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
    • 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
    • Railway Clinical Hospital at Station Samara OAO Rzhd
  • St. Petersburg, Russian Federation
    • City Polyclinic #38
  • Stavropol, Russian Federation
    • Stavropol State Medical Academy
• Serbia
  • 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, 37076
      • 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
• Mild to moderate UC

Exclusion Criteria:

• Disease limited to proctitis <15 cm
• Short bowel syndrome
• Prior colon resection surgery
• History of severe/fulminant UC
• Evidence of other forms of inflammatory bowel disease
• Infectious disease (including human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV])
• 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 or 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
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo
Experimental: Mesalamine; 4 g extended release granules (sachet)	Drug: Mesalamine; Other Names: Pentasa; Mesalazine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects With Remission	The proportion of subjects with remission was defined by the Clinical and Endoscopic Response Score: 0 for rectal bleeding; 0 or 1 with at least 1 point decrease from baseline for stool frequency; 0 or 1 for endoscopic score. The Clinical and Endoscopic Response Score ranged between 0-9, higher scores indicating greater disease severity. This score had two components: Clinical Response which assessed subject's symptoms and ranged between 0-6, and Endoscopic Response which assessed objective evidence of inflammation and ranged between 0-3. Further, the Clinical Response component included two subscales: stool frequency and rectal bleeding (each ranged between 0-3 each) obtained from subjects' daily records. The Endoscopic Response component had one subscale: flexible sigmoidoscopy/colonoscopy (ranging between 0-3).	At Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects With Remission in the Primary Endpoint and the Physician's Global Assessment (PGA) Score of ≤1 (Modified Mayo Score)	The Modified Mayo score was calculated as the sum of the Clinical and Endoscopic Response Score (Range: 0-9, and the standard PGA score (range: 0-3; normal [score=0], mild disease [score=1], moderate disease [score=2], severe disease [score=3]). The statistical test was to be conducted only if the primary analysis was significant.	At Week 8
Time to Cessation of Rectal Bleeding	Defined as time in days from randomization to the first day of 3 consecutive days with a rectal bleeding score of 0, based on subject's daily diary. The statistical test was to be conducted only if the primary analysis was significant.	Up to Week 8
The Proportion of Subjects With Endoscopic Improvement	Defined as an Endoscopic Response Score of 0 or 1, with at least a 1 point reduction from baseline in the endoscopic score at Week 8.	At Week 8
The Proportion of Subjects in Clinical Remission at Weeks 2, 4, and 8	Defined as a score of 0 for rectal bleeding and 0 or 1 with at least 1 point decrease from baseline for stool frequency in the Clinical Response Score subset.	At Week 2, 4, and 8
Time to Normal Stool Pattern	Defined as time in days from randomization to the first day of 3 consecutive days with a stool frequency score of 0, based on subject daily diary.	Up to Week 8
The Change From Baseline in Rectal Bleeding Score at Weeks 2, 4, and 8	Defined as change from baseline in rectal bleeding score at Week 2, 4, and 8 based on subject daily diary. Rectal Bleeding Score is graded 0-3, where 0 is best.	From baseline to Week 2, 4, and 8
The Change From Baseline in Serum C-reactive Protein (CRP) Levels at Weeks 2, 4, and 8	The adjusted mean changes in serum CRP levels from baseline and their difference between treatment groups are presented for each time point.	From baseline to Week 2, 4, and 8
The Change From Baseline in Fecal Calprotectin Levels at Week 8	The adjusted mean change from baseline in fecal calprotectin levels at Week 8 are presented.	From baseline to Week 8
The Change From Baseline in Health Related Quality of Life (QoL) Scores	The change from baseline to Week 2, 4, and 8 in Inflammatory Bowel Disease Questionnaire (IBDQ) scores. The adjusted changes from baseline and their differences between treatment groups are presented. The IBDQ is an instrument used to assess quality of life in adult patients with UC. Subjects were asked to recall symptoms and QoL from last two weeks and to rate each item on a 7- point Likert score (higher scores equate to higher QoL).	From baseline to Week 2, 4, and 8
Number of Participants Experiencing Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a subject taking part in a clinical trial. A 'treatment-emergent AE (TEAE)' is defined as an AE which occurs in the time interval from initial dosing (investigational medicinal product [IMP] intake) to the end of treatment visit. Proportion of subjects with any TEAE (serious or non-serious) are presented.	Up to Week 16
Severity of Adverse Events	The proportion of subjects with intensity of AEs (classified as mild, moderate or severe) are presented.	Up to Week 16
Proportion of Subject With Abnormal Laboratory Values (Hematology)	Proportion of subjects with markedly abnormal changes from baseline in hematology values are presented. >= greater than equal to; <= less than equal to.	Up to Week 16
Proportion of Subjects With Abnormal Laboratory Values (Coagulation)	Proportion of subjects with markedly abnormal changes from baseline values in coagulation laboratory values are presented. INR= International normalized ratio.	Up to Week 16
Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry)	Proportion of subjects with markedly abnormal changes in serum chemistry laboratory values are presented. ALT= Alanine aminotransferase; AST= Aspartate aminotransferase; BUN= Blood urea nitrogen; GGT= Gamma glutamyl transferase.	Up to Week 16

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): February 6, 2018
• Study Completion (Actual): April 3, 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): March 15, 2021
• Last Update Submitted That Met QC Criteria: February 19, 2021
• Last Verified: February 1, 2021

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: 000174; 2015-002557-35 (EudraCT Number)