Ulcerative Colitis
Conditions
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.
Interventions
DRUGMesalamine
DRUGPlacebo
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
| 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 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. |
| 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. |
| 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. |
| 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). |
| 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 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 (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. |
| 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 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. |
Countries
Bulgaria, Canada, Hungary, Latvia, Mexico, Poland, Russia, Serbia, Switzerland, Ukraine, United States
Participant flow
Recruitment details
A total of 71 sites in 10 countries (Bulgaria, Canada, Hungary, Latvia, Mexico, Russia, Serbia, Switzerland, Ukraine, and United States) recruited subjects to this trial between October 2015 to November 2017, the last subject completed last visit in April 2018.
Pre-assignment details
A total of 411 subjects were screened, of which 228 subjects were randomized in a 1:1 ratio to either mesalamine or placebo group (114 subjects each), for 8 weeks double-blind treatment. Subjects who completed 8 weeks but failed to meet the defined criteria for remission received open-label treatment with mesalamine for additional 8 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Mesalamine Mesalamine 4 g extended release granules (sachet), administered orally QD | 114 |
| Placebo Placebo 4 g to match mesalamine extended release granules, administered orally QD | 114 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind | Adverse Event | 1 | 10 |
| Double-blind | Lack of Efficacy | 0 | 2 |
| Double-blind | Lost to Follow-up | 1 | 0 |
| Double-blind | Protocol Deviation | 1 | 0 |
| Double-blind | Protocol Violation | 0 | 1 |
| Double-blind | Withdrawal by Subject | 8 | 11 |
| Open-label | Adverse Event | 2 | 1 |
| Open-label | Lack of Efficacy | 1 | 1 |
| Open-label | Lost to Follow-up | 0 | 1 |
| Open-label | Protocol Violation | 0 | 1 |
| Open-label | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Mesalamine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 9 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 107 Participants | 105 Participants | 212 Participants |
| Age, Continuous | 41.2 years STANDARD_DEVIATION 13.09 | 43.9 years STANDARD_DEVIATION 13.68 | 42.5 years STANDARD_DEVIATION 13.42 |
| Body Mass Index (BMI) | 24.68 kg/m^2 STANDARD_DEVIATION 4.546 | 24.63 kg/m^2 STANDARD_DEVIATION 4.578 | 24.66 kg/m^2 STANDARD_DEVIATION 4.552 |
| Endoscopic Response Score | 2.7 scores on a scale STANDARD_DEVIATION 0.47 | 2.6 scores on a scale STANDARD_DEVIATION 0.48 | 2.7 scores on a scale STANDARD_DEVIATION 0.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 9 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 105 Participants | 105 Participants | 210 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 105 Participants | 103 Participants | 208 Participants |
| Rectal Bleeding Score | 1.2 scores on a scale STANDARD_DEVIATION 0.54 | 1.2 scores on a scale STANDARD_DEVIATION 0.58 | 1.2 scores on a scale STANDARD_DEVIATION 0.55 |
| Sex: Female, Male Female | 57 Participants | 64 Participants | 121 Participants |
| Sex: Female, Male Male | 57 Participants | 50 Participants | 107 Participants |
| Stool Frequency Score | 1.6 scores on a scale STANDARD_DEVIATION 0.81 | 1.8 scores on a scale STANDARD_DEVIATION 0.78 | 1.7 scores on a scale STANDARD_DEVIATION 0.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 114 | 0 / 114 | 0 / 170 |
| other Total, other adverse events | 19 / 114 | 13 / 114 | 8 / 170 |
| serious Total, serious adverse events | 1 / 114 | 0 / 114 | 2 / 170 |
Outcome results
Primary
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).
Time frame: At Week 8
Population: The ITT analysis set comprised all randomized subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mesalamine | Proportion of Subjects With Remission | 19 Participants |
| Placebo | Proportion of Subjects With Remission | 13 Participants |
Comparison: Proportions were compared between treatment groups, at a two-sided 0.05 significance level.p-value: >0.0595% CI: [0.73, 3.32]Chi-squared
Secondary
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.
Time frame: Up to Week 16
Population: The safety analysis set comprised all subjects who received at least 1 dose of IMP, and was analyzed according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mesalamine | Number of Participants Experiencing Adverse Events | Any TEAE | 28 Participants |
| Mesalamine | Number of Participants Experiencing Adverse Events | Serious AE | 1 Participants |
| Placebo | Number of Participants Experiencing Adverse Events | Any TEAE | 37 Participants |
| Placebo | Number of Participants Experiencing Adverse Events | Serious AE | 0 Participants |
| Mesalamine (Open-Label) | Number of Participants Experiencing Adverse Events | Any TEAE | 31 Participants |
| Mesalamine (Open-Label) | Number of Participants Experiencing Adverse Events | Serious AE | 2 Participants |
Secondary
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.
Time frame: Up to Week 16
Population: The safety analysis set comprised all subjects who received at least 1 dose of IMP, and was analyzed according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Coagulation) | Prothrombin INR, Normal >1.1 to Abnormal | 14 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Coagulation) | Prothrombin INR, Normal <0.8 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Coagulation) | Prothrombin INR, High >1.1 to Abnormal | 4 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Coagulation) | Prothrombin INR, Normal >1.1 to Abnormal | 14 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Coagulation) | Prothrombin INR, Normal <0.8 to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Coagulation) | Prothrombin INR, High >1.1 to Abnormal | 10 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Coagulation) | Prothrombin INR, Normal <0.8 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Coagulation) | Prothrombin INR, High >1.1 to Abnormal | 22 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Coagulation) | Prothrombin INR, Normal >1.1 to Abnormal | 28 Participants |
Secondary
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.
Time frame: Up to Week 16
Population: The safety analysis set comprised all subjects who received at least 1 dose of IMP, and was analyzed according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Bilirubin (mg/dL), High >=1.5xULN to Abnormal | 2 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | AST (U/L), Normal >3xULN to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | AST (U/L), High >3xULN to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Bilirubin (mg/dL), Normal >=1.5xULN to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | ALT (U/L), Normal >3xULN to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | BUN (mg/dL), Normal >=10.7 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Calcium (mg/dL), Normal <=1.8 to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Chloride (mmol/L), Normal >=115 to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Chloride (mmol/L), High >=115 to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | GGT (U/L), High >3xULN to Abnormal | 2 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Glucose (mg/dL), Normal >=10 to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Glucose (mg/dL), High >=10 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Potassium (mmol/L), Normal <=3.0 to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Potassium (mmol/L), Normal >=5.8 to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Potassium (mmol/L), High >=5.8 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Sodium (mmol/L), Low<=130 to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | BUN (mg/dL), Normal >=10.7 to Abnormal | 1 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Calcium (mg/dL), Normal <=1.8 to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Chloride (mmol/L), Normal >=115 to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Potassium (mmol/L), Normal >=5.8 to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Chloride (mmol/L), High >=115 to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | GGT (U/L), High >3xULN to Abnormal | 2 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Sodium (mmol/L), Low<=130 to Abnormal | 1 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Glucose (mg/dL), Normal >=10 to Abnormal | 1 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | ALT (U/L), Normal >3xULN to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Potassium (mmol/L), High >=5.8 to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | AST (U/L), Normal >3xULN to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Glucose (mg/dL), High >=10 to Abnormal | 2 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | AST (U/L), High >3xULN to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Bilirubin (mg/dL), Normal >=1.5xULN to Abnormal | 0 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Bilirubin (mg/dL), High >=1.5xULN to Abnormal | 1 Participants |
| Placebo | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Potassium (mmol/L), Normal <=3.0 to Abnormal | 0 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Glucose (mg/dL), Normal >=10 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | BUN (mg/dL), Normal >=10.7 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Potassium (mmol/L), Normal <=3.0 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | AST (U/L), High >3xULN to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Calcium (mg/dL), Normal <=1.8 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Sodium (mmol/L), Low<=130 to Abnormal | 0 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | ALT (U/L), Normal >3xULN to Abnormal | 2 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Chloride (mmol/L), Normal >=115 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Glucose (mg/dL), High >=10 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Bilirubin (mg/dL), High >=1.5xULN to Abnormal | 4 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Chloride (mmol/L), High >=115 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Potassium (mmol/L), Normal >=5.8 to Abnormal | 3 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | AST (U/L), Normal >3xULN to Abnormal | 2 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | GGT (U/L), High >3xULN to Abnormal | 4 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Bilirubin (mg/dL), Normal >=1.5xULN to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subjects With Abnormal Laboratory Values (Serum Chemistry) | Potassium (mmol/L), High >=5.8 to Abnormal | 1 Participants |
Secondary
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.
Time frame: At Week 8
Population: The ITT analysis set comprised all randomized subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mesalamine | Proportion of Subjects With Remission in the Primary Endpoint and the Physician's Global Assessment (PGA) Score of ≤1 (Modified Mayo Score) | 19 Participants |
| Placebo | Proportion of Subjects With Remission in the Primary Endpoint and the Physician's Global Assessment (PGA) Score of ≤1 (Modified Mayo Score) | 11 Participants |
Secondary
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.
Time frame: Up to Week 16
Population: The safety analysis set comprised all subjects who received at least 1 dose of IMP, and was analyzed according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hematocrit (%), Normal<=0.32 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Erythrocytes (10^6/uL), Low<=3.5 to Abnormal | 2 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Erythrocytes (10^6/uL), Normal<=3.5 to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hematocrit (%), Low<=0.32 to Abnormal | 4 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Eosinophils/Leukocytes (%), Normal>=10 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hematocrit (%), Normal>=0.56 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hemoglobin (g/dL), Low<=115 to Abnormal | 21 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hemoglobin (g/dL), Normal<=115 to Abnormal | 12 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Leukocytes (10^3/uL), Normal <=2.8 to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Leukocytes (10^3/uL), Normal >=16.0 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Leukocytes (10^3/uL), High >=16.0 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Lymphocytes/Leukocytes (%), Low<=10 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Lymphocytes/Leukocytes (%), Normal<=10 to Abnormal | 4 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Lymphocytes/Leukocytes (%), High>=80 to Abnormal | 1 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Neutrophils/Leukocyte (%), Normal<=15 to Abnormal | 2 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Neutrophils/Leukocyte (%), Normal>=90 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Neutrophils/Leukocyte (%), High >=90 to Abnormal | 0 Participants |
| Mesalamine | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Platelets (10^3/uL), High>=700 to Abnormal | 2 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Platelets (10^3/uL), High>=700 to Abnormal | 0 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Eosinophils/Leukocytes (%), Normal>=10 to Abnormal | 2 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Leukocytes (10^3/uL), Normal >=16.0 to Abnormal | 2 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Lymphocytes/Leukocytes (%), Normal<=10 to Abnormal | 2 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Erythrocytes (10^6/uL), Low<=3.5 to Abnormal | 4 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Neutrophils/Leukocyte (%), Normal<=15 to Abnormal | 0 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Neutrophils/Leukocyte (%), Normal>=90 to Abnormal | 1 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Erythrocytes (10^6/uL), Normal<=3.5 to Abnormal | 0 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Leukocytes (10^3/uL), High >=16.0 to Abnormal | 1 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Neutrophils/Leukocyte (%), High >=90 to Abnormal | 1 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hematocrit (%), Low<=0.32 to Abnormal | 1 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Leukocytes (10^3/uL), Normal <=2.8 to Abnormal | 0 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Lymphocytes/Leukocytes (%), High>=80 to Abnormal | 0 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hematocrit (%), Normal<=0.32 to Abnormal | 3 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hemoglobin (g/dL), Normal<=115 to Abnormal | 15 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Lymphocytes/Leukocytes (%), Low<=10 to Abnormal | 3 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hematocrit (%), Normal>=0.56 to Abnormal | 1 Participants |
| Placebo | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hemoglobin (g/dL), Low<=115 to Abnormal | 23 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hematocrit (%), Normal>=0.56 to Abnormal | 0 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hemoglobin (g/dL), Low<=115 to Abnormal | 37 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hemoglobin (g/dL), Normal<=115 to Abnormal | 29 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Neutrophils/Leukocyte (%), Normal<=15 to Abnormal | 2 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Leukocytes (10^3/uL), Normal <=2.8 to Abnormal | 2 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Platelets (10^3/uL), High>=700 to Abnormal | 2 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Leukocytes (10^3/uL), Normal >=16.0 to Abnormal | 2 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Leukocytes (10^3/uL), High >=16.0 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Neutrophils/Leukocyte (%), Normal>=90 to Abnormal | 2 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Lymphocytes/Leukocytes (%), Low<=10 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Eosinophils/Leukocytes (%), Normal>=10 to Abnormal | 4 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Erythrocytes (10^6/uL), Low<=3.5 to Abnormal | 4 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Lymphocytes/Leukocytes (%), Normal<=10 to Abnormal | 6 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Erythrocytes (10^6/uL), Normal<=3.5 to Abnormal | 2 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hematocrit (%), Low<=0.32 to Abnormal | 5 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Hematocrit (%), Normal<=0.32 to Abnormal | 4 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Lymphocytes/Leukocytes (%), High>=80 to Abnormal | 1 Participants |
| Mesalamine (Open-Label) | Proportion of Subject With Abnormal Laboratory Values (Hematology) | Neutrophils/Leukocyte (%), High >=90 to Abnormal | 1 Participants |
Secondary
Severity of Adverse Events
The proportion of subjects with intensity of AEs (classified as mild, moderate or severe) are presented.
Time frame: Up to Week 16
Population: The safety analysis set comprised all subjects who received at least 1 dose of IMP, and was analyzed according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mesalamine | Severity of Adverse Events | Moderate | 6 Participants |
| Mesalamine | Severity of Adverse Events | Mild | 23 Participants |
| Mesalamine | Severity of Adverse Events | Severe | 5 Participants |
| Placebo | Severity of Adverse Events | Moderate | 15 Participants |
| Placebo | Severity of Adverse Events | Mild | 27 Participants |
| Placebo | Severity of Adverse Events | Severe | 3 Participants |
| Mesalamine (Open-Label) | Severity of Adverse Events | Mild | 21 Participants |
| Mesalamine (Open-Label) | Severity of Adverse Events | Severe | 1 Participants |
| Mesalamine (Open-Label) | Severity of Adverse Events | Moderate | 11 Participants |
Secondary
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.
Time frame: From baseline to Week 8
Population: The ITT analysis set comprised all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mesalamine | The Change From Baseline in Fecal Calprotectin Levels at Week 8 | -144.93 ug/g | Standard Deviation 854.41 |
| Placebo | The Change From Baseline in Fecal Calprotectin Levels at Week 8 | -119.56 ug/g | Standard Deviation 1083.69 |
Comparison: Changes from baseline were compared between treatment groups, at a two-sided 0.05 significance level.p-value: <0.0595% CI: [-514.96, -64.42]ANCOVA
Secondary
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).
Time frame: From baseline to Week 2, 4, and 8
Population: The ITT analysis set comprised randomized subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mesalamine | The Change From Baseline in Health Related Quality of Life (QoL) Scores | Week 2 | 24.79 points on a score | Standard Deviation 25.92 |
| Mesalamine | The Change From Baseline in Health Related Quality of Life (QoL) Scores | Week 4 | 33.58 points on a score | Standard Deviation 29.69 |
| Mesalamine | The Change From Baseline in Health Related Quality of Life (QoL) Scores | Week 8 | 34.41 points on a score | Standard Deviation 37.23 |
| Placebo | The Change From Baseline in Health Related Quality of Life (QoL) Scores | Week 2 | 18.75 points on a score | Standard Deviation 33.87 |
| Placebo | The Change From Baseline in Health Related Quality of Life (QoL) Scores | Week 4 | 28.13 points on a score | Standard Deviation 33.08 |
| Placebo | The Change From Baseline in Health Related Quality of Life (QoL) Scores | Week 8 | 24.73 points on a score | Standard Deviation 36.42 |
Comparison: Change from baseline scores were compared between treatment groups over 8 weeks, at a two-sided 0.05 significance level.p-value: <0.0595% CI: [5.1, 20.5]Repeated-measures ANCOVA
Secondary
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.
Time frame: From baseline to Week 2, 4, and 8
Population: The ITT analysis set comprised randomized subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mesalamine | The Change From Baseline in Rectal Bleeding Score at Weeks 2, 4, and 8 | Week 2 | -0.39 scores on a scale | Standard Deviation 0.68 |
| Mesalamine | The Change From Baseline in Rectal Bleeding Score at Weeks 2, 4, and 8 | Week 4 | -0.56 scores on a scale | Standard Deviation 0.72 |
| Mesalamine | The Change From Baseline in Rectal Bleeding Score at Weeks 2, 4, and 8 | Week 8 | -0.64 scores on a scale | Standard Deviation 0.8 |
| Placebo | The Change From Baseline in Rectal Bleeding Score at Weeks 2, 4, and 8 | Week 2 | -0.23 scores on a scale | Standard Deviation 0.84 |
| Placebo | The Change From Baseline in Rectal Bleeding Score at Weeks 2, 4, and 8 | Week 4 | -0.34 scores on a scale | Standard Deviation 0.92 |
| Placebo | The Change From Baseline in Rectal Bleeding Score at Weeks 2, 4, and 8 | Week 8 | -0.35 scores on a scale | Standard Deviation 0.84 |
Comparison: Change from baseline scores were compared between treatment groups over 8 weeks, at a two-sided 0.05 significance level.p-value: <0.0595% CI: [-0.41, -0.08]Repeated-measures ANCOVA
Secondary
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.
Time frame: From baseline to Week 2, 4, and 8
Population: The ITT analysis set comprise all randomized subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mesalamine | The Change From Baseline in Serum C-reactive Protein (CRP) Levels at Weeks 2, 4, and 8 | Week 4 | -0.86 mg/L | Standard Deviation 16.52 |
| Mesalamine | The Change From Baseline in Serum C-reactive Protein (CRP) Levels at Weeks 2, 4, and 8 | Week 2 | 0.60 mg/L | Standard Deviation 13.52 |
| Mesalamine | The Change From Baseline in Serum C-reactive Protein (CRP) Levels at Weeks 2, 4, and 8 | Week 8 | -2.01 mg/L | Standard Deviation 13.09 |
| Placebo | The Change From Baseline in Serum C-reactive Protein (CRP) Levels at Weeks 2, 4, and 8 | Week 2 | 0.25 mg/L | Standard Deviation 19.67 |
| Placebo | The Change From Baseline in Serum C-reactive Protein (CRP) Levels at Weeks 2, 4, and 8 | Week 4 | -1.05 mg/L | Standard Deviation 16.27 |
| Placebo | The Change From Baseline in Serum C-reactive Protein (CRP) Levels at Weeks 2, 4, and 8 | Week 8 | -0.73 mg/L | Standard Deviation 22.51 |
Comparison: Change from baseline scores were compared between treatment groups over 8 weeks, at a two-sided 0.05 significance level.p-value: >0.0595% CI: [-5.46, 0.67]Repeated-measures ANCOVA
Secondary
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.
Time frame: At Week 2, 4, and 8
Population: The ITT analysis comprised all randomized subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mesalamine | The Proportion of Subjects in Clinical Remission at Weeks 2, 4, and 8 | Week 2 | 19 Participants |
| Mesalamine | The Proportion of Subjects in Clinical Remission at Weeks 2, 4, and 8 | Week 4 | 29 Participants |
| Mesalamine | The Proportion of Subjects in Clinical Remission at Weeks 2, 4, and 8 | Week 8 | 40 Participants |
| Placebo | The Proportion of Subjects in Clinical Remission at Weeks 2, 4, and 8 | Week 2 | 17 Participants |
| Placebo | The Proportion of Subjects in Clinical Remission at Weeks 2, 4, and 8 | Week 4 | 26 Participants |
| Placebo | The Proportion of Subjects in Clinical Remission at Weeks 2, 4, and 8 | Week 8 | 28 Participants |
Comparison: Proportions were compared between treatment groups over 8 weeks, at a two-sided 0.05 significance level.p-value: >0.0595% CI: [0.78, 2.15]Generalized estimating equation approach
Secondary
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.
Time frame: At Week 8
Population: The ITT analysis set comprised randomized subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mesalamine | The Proportion of Subjects With Endoscopic Improvement | 34 Participants |
| Placebo | The Proportion of Subjects With Endoscopic Improvement | 22 Participants |
Comparison: Proportions were compared between treatment groups at a two-sided 0.05 significance level.p-value: >0.0595% CI: [0.96, 3.29]Chi-squared
Secondary
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.
Time frame: Up to Week 8
Population: The ITT analysis set comprised all randomized subjects.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mesalamine | Time to Cessation of Rectal Bleeding | 18.0 days |
| Placebo | Time to Cessation of Rectal Bleeding | 43.0 days |
Secondary
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.
Time frame: Up to Week 8
Population: The ITT analysis set comprised randomized subjects.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mesalamine | Time to Normal Stool Pattern | 55.0 days |
| Placebo | Time to Normal Stool Pattern | NA days |
Comparison: Times to normal stool pattern were compared between treatment groups, at a two-sided 0.05 significance level.p-value: >0.0595% CI: [0.91, 2.02]Log Rank