NCT02522780

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

Completed Phase 3 Results posted Last updated 8 November 2021

What this trial tests

Phase 3 trial testing Mesalamine in Ulcerative Colitis in 276 participants. Completed in 19 September 2018.

Timeline

1 February 2016

Primary endpoint
19 September 2018

19 September 2018

Quick facts

Lead sponsor	Ferring Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	276
Start date	1 February 2016
Primary completion	19 September 2018
Estimated completion	19 September 2018
Sites	96 locations across Russia, Ukraine, Serbia, Hungary, Mexico, Poland, Canada, Switzerland

Drugs / interventions tested

• Mesalamine — full drug profile →
• Placebo

Conditions studied

• Ulcerative Colitis — all drugs for Ulcerative Colitis →

Sponsor

Ferring Pharmaceuticals — full company profile →

Who can join

Adults 18 to 75, any sex, with Ulcerative Colitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Proportion of Subjects With Remission at Month 6 Primary · 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 mo

Group	Value	95% CI
Mesalamine	82
Placebo.	67

Proportion of Subjects in Clinical Remission at Month 2, 4, and 6 Secondary · 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

Month 2

Group	Value	95% CI
Mesalamine	122
Placebo	116

Month 4

Group	Value	95% CI
Mesalamine	113
Placebo	113

Month 6

Group	Value	95% CI
Mesalamine	96
Placebo	89

Time to Relapse Secondary · Time from randomization to the day of withdrawal due to escalation of therapy (up to 6 months)

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.

Group	Value	95% CI
Mesalamine	NA	NA – NA
Placebo	NA	NA – NA

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 Secondary · 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 num

Group	Value	95% CI
Mesalamine	14
Placebo	30

Change From Baseline in Serum C-reactive Protein (CRP) Levels at Month 2, 4, and 6 Secondary · Baseline, 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.

Month 2

Group	Value	95% CI
Mesalamine	0.8	± 4.76
Placebo	2.2	± 15.63

Month 4

Group	Value	95% CI
Mesalamine	1.0	± 5.69
Placebo	0.9	± 5.53

Month 6

Group	Value	95% CI
Mesalamine	0.8	± 3.67
Placebo	2.5	± 16.66

Change From Baseline in Fecal Calprotectin Levels at Month 2, 4, and 6 Secondary · Baseline, 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.

Month 2

Group	Value	95% CI
Mesalamine	-94.8	± 553.00
Placebo	12.8	± 509.70

Month 4

Group	Value	95% CI
Mesalamine	-41.7	± 533.02
Placebo	53.6	± 581.64

Month 6

Group	Value	95% CI
Mesalamine	-43.5	± 553.13
Placebo	36.4	± 559.98

Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Scores at Months 2, 4, and 6 Secondary · Baseline, Month 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 in

Month 2

Group	Value	95% CI
Mesalamine	-1.3	± 17.78
Placebo	-0.4	± 20.00

Month 4

Group	Value	95% CI
Mesalamine	-0.6	± 20.40
Placebo	-0.3	± 18.53

Month 6

Group	Value	95% CI
Mesalamine	-0.5	± 24.80
Placebo	-1.2	± 23.44

Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · Up to Month 6

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

Any Treatment-Emergent AEs

Group	Value	95% CI
Mesalamine	42
Placebo	49

Treatment-Emergent SAEs

Group	Value	95% CI
Mesalamine	2
Placebo	3

Severity of Adverse Events Secondary · Up to Month 6

The number of subjects with intensity of AEs (classified as mild, moderate or severe) were presented. Data is presented cumulative for all pathways.

Mild

Group	Value	95% CI
Mesalamine	32
Placebo	32

Moderate

Group	Value	95% CI
Mesalamine	18
Placebo	22

Severe

Group	Value	95% CI
Mesalamine	2
Placebo	3

Proportion of Subjects With Markedly Abnormal Laboratory Values: Hematology Secondary · Baseline, Month 6

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.

Basophils/Leukocytes: >=5%

Group	Value	95% CI
Mesalamine	0
Placebo	1

Eosinophils/Leukocytes: >=10%

Group	Value	95% CI
Mesalamine	3
Placebo	7

Erythrocytes: <=3.5*10^6/μL

Group	Value	95% CI
Mesalamine	2
Placebo	1

Hematocrit: <=0.32%

Group	Value	95% CI
Mesalamine	1
Placebo	0

Hematocrit: >=0.56%

Group	Value	95% CI
Mesalamine	8
Placebo	12

Hemoglobin: <=11.5 g/dL

Group	Value	95% CI
Mesalamine	29
Placebo	23

Leukocytes: <=2.8*10^3/μL

Group	Value	95% CI
Mesalamine	4
Placebo	4

Leukocytes: >=16.0*10^3/μL

Group	Value	95% CI
Mesalamine	2
Placebo	0

Proportion of Subjects With Markedly Abnormal Laboratory Values: Coagulation Secondary · Baseline, Month 6

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.

aPTT: >70 sec

Group	Value	95% CI
Mesalamine	0
Placebo	0

Prothrombin INR: <0.8

Group	Value	95% CI
Mesalamine	0
Placebo	2

Prothrombin INR: >1.1

Group	Value	95% CI
Mesalamine	46
Placebo	54

Proportion of Subjects With Markedly Abnormal Laboratory Values: Serum Chemistry Secondary · Baseline, Month 6

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

ALT: >3*ULN

Group	Value	95% CI
Mesalamine	1
Placebo	1

ALP: >3*ULN & 25% inc from BL

Group	Value	95% CI
Mesalamine	0
Placebo	0

AST: >3*ULN

Group	Value	95% CI
Mesalamine	2
Placebo	2

Bilirubin: >=1.5*ULN

Group	Value	95% CI
Mesalamine	8
Placebo	5

Blood Urea Nitrogen: >=10.7 mg/dL

Group	Value	95% CI
Mesalamine	8
Placebo	11

Calcium: <=1.8 mg/dL

Group	Value	95% CI
Mesalamine	0
Placebo	0

Calcium: >=3.9 mg/dL

Group	Value	95% CI
Mesalamine	9
Placebo	12

Chloride: <=90 mmol/L

Group	Value	95% CI
Mesalamine	0
Placebo	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Month 6. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Mesalamine

Serious: 2/137 (1%)

Deaths: 0/137

Placebo

Serious: 3/135 (2%)

Deaths: 0/135

Serious adverse events (6 terms)

Reaction	System	Mesalamine	Placebo
Hypertension	Vascular disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Colitis ulcerative	Gastrointestinal disorders	—	—
Ecthyma	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—

Other adverse events (6 terms — click to expand)

Reaction	System	Mesalamine	Placebo
Colitis ulcerative	Gastrointestinal disorders	—	—
Glomerular filtration rate decreased	Investigations	—	—
Alanine aminotransferase increased	Investigations	—	—
Gamma-glutamyltransferase increased	Investigations	—	—
Faecal calprotectin increased	Investigations	—	—
Respiratory tract infection viral	Infections and infestations	—	—

Most-reported serious reactions: Hypertension, Acute myocardial infarction, Colitis ulcerative, Ecthyma, Pneumonia, Sepsis.

Data from ClinicalTrials.gov NCT02522780 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.
   Murray A, Nguyen TM, Parker CE, Feagan BG, et al · · 2020 · cited 61× · PMID 32856298 · DOI 10.1002/14651858.cd000544.pub5