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

Phase 3

Completed

Conditions: Ulcerative Colitis

Interventions: Drug: Placebo
Drug: Mesalamine

Registration Number: NCT02522767

Lead Sponsor: Ferring Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 228

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo
Mesalamine	Mesalamine	4 g extended release granules (sachet)

Primary Outcome Measures

Name	Time	Method
Proportion of Subjects With Remission	At Week 8	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).

Secondary Outcome Measures

Name	Time	Method
The Proportion of Subjects With Endoscopic Improvement	At Week 8	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.
Time to Normal Stool Pattern	Up to Week 8	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.
The Change From Baseline in Fecal Calprotectin Levels at Week 8	From baseline to Week 8	The adjusted mean change from baseline in fecal calprotectin levels at Week 8 are presented.
The Change From Baseline in Health Related Quality of Life (QoL) Scores	From baseline to Week 2, 4, and 8	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).
Proportion of Subjects With Abnormal Laboratory Values (Coagulation)	Up to Week 16	Proportion of subjects with markedly abnormal changes from baseline values in coagulation laboratory values are presented. INR= International normalized ratio.
The Change From Baseline in Rectal Bleeding Score at Weeks 2, 4, and 8	From baseline to Week 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.
Proportion of Subject With Abnormal Laboratory Values (Hematology)	Up to Week 16	Proportion of subjects with markedly abnormal changes from baseline in hematology values are presented. \>= greater than equal to; \<= less than equal to.
Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry)	Up to Week 16	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.
The Change From Baseline in Serum C-reactive Protein (CRP) Levels at Weeks 2, 4, and 8	From baseline to Week 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.
Time to Cessation of Rectal Bleeding	Up to Week 8	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.
The Proportion of Subjects in Clinical Remission at Weeks 2, 4, and 8	At Week 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.
Number of Participants Experiencing Adverse Events	Up to Week 16	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.
Severity of Adverse Events	Up to Week 16	The proportion of subjects with intensity of AEs (classified as mild, moderate or severe) are presented.
Proportion of Subjects With Remission in the Primary Endpoint and the Physician's Global Assessment (PGA) Score of ≤1 (Modified Mayo Score)	At Week 8	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.

Trial Locations

Locations (90): Research Associates of South Florida, LLC
🇺🇸
Miami, Florida, United States
Biopharma Informatic Inc.
🇺🇸
Houston, Texas, United States
Medical Research Center of Florida
🇺🇸
Pembroke Pines, Florida, United States
DM Clinical Research
🇺🇸
Tomball, Texas, United States
New River Valley Research Institute
🇺🇸
Christiansburg, Virginia, United States
Medical Center Excelsior OOD
🇧🇬
Sevlievo, Bulgaria
Riga East Clinical University Hospital
🇱🇻
Riga, Latvia
Investigational site
🇨🇭
Bern, Switzerland
Centrum Zdrowia Matki, Dziecka i Mlodziezy
🇵🇱
Warsaw, Poland
Omsk State Medical Academy
🇷🇺
Omsk, Russian Federation
State Budget Institution of Ryazan region" Regional Clinical Hospital"
🇷🇺
Ryazan, Russian Federation
Inselspital Bern
🇨🇭
Bern, Switzerland
University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna - ISUL EAD
🇧🇬
Sofia, Bulgaria
Polana-D, LTD
🇱🇻
Daugavpils, Latvia
SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
🇵🇱
Lodz, Poland
Private Enterprise Private Manufactire Company "Acinus".
🇺🇦
Kirovohrad, Ukraine
Magyar Honvédség Egészségügyi Központ
🇭🇺
Budapest, Hungary
City Clinic University Multiprofile Hospital for Active Treatment EOOD
🇧🇬
Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment Sv Ivan Rilski EAD
🇧🇬
Sofia, Bulgaria
Maria Auxiliadora Hospital
🇲🇽
Guadalajara, Mexico
Novosibirsk State Medical University
🇷🇺
Novosibirsk, Russian Federation
City Clinical Hospital #51
🇷🇺
Moscow, Russian Federation
Digestive Diseases Centre Gastro
🇱🇻
Riga, Latvia
Rostov State Medical University
🇷🇺
Rostov-on-Don, Russian Federation
Diagnostic Consultative Centre Mladost M OOD
🇧🇬
Varna, Bulgaria
Semmelweis Egyetem Institute
🇭🇺
Budapest, Hungary
Karolina Korhaz Rendelointezet
🇭🇺
Mosonmagyarovar, Hungary
Latvian Maritime Medicine Centre
🇱🇻
Riga, Latvia
Osrodek Medycyny Rodzinnej Sp. z o.o.
🇵🇱
Sobótka, Dolnoslaskie, Poland
Niepubliczny Zaklad Opieki Zdrowotnej Intermed
🇵🇱
Czestochowa, Poland
Niepubliczny Zaklad Opieki Zdrowotnej CENTRUM MEDYCZNE Szpital Swietej Rodziny
🇵🇱
Lodz, Poland
Nizhegorodskaya Regional Clinical Hospital n.a. Semashko
🇷🇺
Nizhny Novgorod, Russian Federation
Stavropol State Medical Academy
🇷🇺
Stavropol, Russian Federation
Clinical Hospital Centar Zvezdara
🇷🇸
Belgrade, Serbia
Municipal Healthcare Institution Kharkiv City Clinical Hospital #2
🇺🇦
Kharkiv, Ukraine
Municipal Institution Odesa Regional Clinical Hospital
🇺🇦
Odesa, Ukraine
Pannónia Magánorvosi Centrum Kft
🇭🇺
Budapest, Hungary
Research Institute of Physiology of Sibirian Branch the RAMS
🇷🇺
Novosibirsk, Russian Federation
Railway Clinical Hospital at Station Samara OAO Rzhd
🇷🇺
Samara, Russian Federation
Medical Center LLC Ukrainian German Antiulcer Gastroenterology Center BIK Kyiv
🇺🇦
Kyiv, Kyïv, Ukraine
Medical Center Universal Clinic Oberih of LLC Kapytal
🇺🇦
Kyiv, Ukraine
Medical Centre of PE First Private Clinic
🇺🇦
Zhytomyr, Ukraine
Russian Medical Military Academy n.a. S.M. Kirov
🇷🇺
Saint Petersburg, Russian Federation
Universitätsspital Zürich
🇨🇭
Zürich, Switzerland
Municipal Institution 6th City Clinical Hospital of Zaporizhzhia City Council
🇺🇦
Zaporizhzhia, Ukraine
Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
🇺🇦
Zaporizhzhia, Ukraine
Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft. Debreceni Egészségügyi Központja
🇭🇺
Debrecen, Hungary
ENDOMEDIX Kft.
🇭🇺
Miskolc, Hungary
BI Research Center
🇺🇸
Houston, Texas, United States
Preferred Research Partners
🇺🇸
Little Rock, Arkansas, United States
IMIC
🇺🇸
Palmetto Bay, Florida, United States
Associates in Gastroenterology, PLC
🇺🇸
Hermitage, Tennessee, United States
United Research Institute
🇺🇸
Murrieta, California, United States
Toronto Digestive Disease Associates
🇨🇦
Vaughan, Canada
Multiprofile Hospital For Active Treatment Avis Medica
🇧🇬
Pleven, Bulgaria
Medical Center-1-Sevlievo EOOD
🇧🇬
Sevlievo, Bulgaria
Medical Center Asklepion - Humane Medicine Research EOOD
🇧🇬
Sofia, Bulgaria
Advanced Research Institute
🇺🇸
Ogden, Utah, United States
Topstone Research Institute
🇨🇦
Ottawa, Ontario, Canada
Clinfan Kft.
🇭🇺
Szekszard, Hungary
City Polyclinic #38
🇷🇺
St. Petersburg, Russian Federation
Kyiv Municipal Clinical Hospital #18
🇺🇦
Kyiv, Ukraine
Kremenchuk city Hospital # n.a O.T.Bohaievskyi
🇺🇦
Kremenchuk, Ukraine
Municipal City Clinical emergency Hospital
🇺🇦
Lviv, Ukraine
Medical Clinical Research Center of Medical Center LLC Health Clinic
🇺🇦
Vinnytsia, Ukraine
Vinnytsia Regional Clinical Hospital Hospital n.a. M.I. Pyrohov
🇺🇦
Vinnytsia, Ukraine
Pauls Stradins Clinical University Hospital
🇱🇻
Riga, Latvia
ICARO Investigaciones en Medicina, S.A de C.V
🇲🇽
Chihuahua, Mexico
Investigación Biomédica para el Desarrollo de Fármacos, S.A. de C.V.
🇲🇽
Zapopan, Mexico
Lexmedica
🇵🇱
Wroclaw, Dolnoslaskie, Poland
Zespół Przychodni Specjalistycznych PRIMA Sp. z o.o.
🇵🇱
Warszawa, Mazowieckie, Poland
Uniwersytecki Szpital Kliniczny w Bialymstoku
🇵🇱
Bialystok, Podlaskie, Poland
Kyiv City Clinical Hospital #8
🇺🇦
Kyiv, Ukraine
Centrum Badan Klinicznych PI-House sp. z o.o.
🇵🇱
Gdansk, Pomorskie, Poland
Economicus - NZOZ ALL-MEDICUS
🇵🇱
Katowice, Poland
Regional Clinical Hospital
🇷🇺
Krasnoyarsk, Russian Federation
Health Center Valjevo
🇷🇸
Valjevo, Serbia
Regional Municipal Institution Chernivtsi Regional Clinical Hospital
🇺🇦
Chernivtsi, Ukraine
SI National Institute of Therapy n.a. L.T. Mala of National Academy of Medical Sciences of Ukraine
🇺🇦
Kharkiv, Ukraine
Municipal Intitution "Kherson City Clinical Hospital n.a. A. and O. Tropinykh"
🇺🇦
Kherson, Ukraine
City Hospital #31
🇷🇺
Saint Petersburg, Russian Federation
Municipal Institution Dnipropetrovsk Regional Clinical Hospital n.a. I.I. Mechnykov
🇺🇦
Dnipropetrovsk, Ukraine
Small Business Private Enterprise Medical Center "Pulse"
🇺🇦
Vinnytsya, Ukraine
Lenus Research and Medical Group
🇺🇸
Sweetwater, Florida, United States
Digestive & Liver Disease Specialists
🇺🇸
Norfolk, Virginia, United States
Digestive Health Center
🇺🇸
Pasadena, Texas, United States
Cumberland Research Associates, LLC
🇺🇸
Fayetteville, North Carolina, United States
Wilmington Gastroenterology Associates
🇺🇸
Wilmington, North Carolina, United States
Clinical Trials of SWLA, LLC
🇺🇸
Lake Charles, Louisiana, United States
Quality Medical Research, PLLC
🇺🇸
Nashville, Tennessee, United States