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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
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
GroupInterventionDescription
PlaceboPlaceboMatching placebo
MesalamineMesalamine4 g extended release granules (sachet)
Primary Outcome Measures
NameTimeMethod
Proportion of Subjects With RemissionAt 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
NameTimeMethod
The Proportion of Subjects With Endoscopic ImprovementAt 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 PatternUp 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 8From 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) ScoresFrom 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 8From 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 8From 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 BleedingUp 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 8At 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 EventsUp 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 EventsUp 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)

Preferred Research Partners

🇺🇸

Little Rock, Arkansas, United States

United Research Institute

🇺🇸

Murrieta, California, United States

Research Associates of South Florida, LLC

🇺🇸

Miami, Florida, United States

IMIC

🇺🇸

Palmetto Bay, Florida, United States

Medical Research Center of Florida

🇺🇸

Pembroke Pines, Florida, United States

Lenus Research and Medical Group

🇺🇸

Sweetwater, Florida, United States

Clinical Trials of SWLA, LLC

🇺🇸

Lake Charles, Louisiana, United States

Cumberland Research Associates, LLC

🇺🇸

Fayetteville, North Carolina, United States

Wilmington Gastroenterology Associates

🇺🇸

Wilmington, North Carolina, United States

Associates in Gastroenterology, PLC

🇺🇸

Hermitage, Tennessee, United States

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Preferred Research Partners
🇺🇸Little Rock, Arkansas, United States

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