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

Ulcerative Colitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02522780
• Other study ID #: 000175
• Secondary ID: 2015-002558-11
• Status: Completed
• Phase: Phase 3
• Start date: February 1, 2016
• Est. completion date: September 19, 2018

Study information

• Verified date: September 2019
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 276
• Est. completion date: September 19, 2018
• Est. primary completion date: September 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Mesalamine
Pharmaceutical form: Granules in sachet; Route of administration: Oral use
• Placebo
Pharmaceutical form: Granules in sachet; Route of administration: Oral use

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Hungary,  Latvia,  Mexico,  Poland,  Russian Federation,  Serbia,  Switzerland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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