Acute Ulcerative Colitis
Conditions
Keywords
UC
Brief summary
The purpose of this research study was to compare the medication TP05 to the medication Asacol™ for the treatment of ulcerative colitis (UC) and to assess the safety and tolerability of TP05. This study investigated whether TP05 is as good as (non-inferior to) Asacol™(1). (1)The trademark Asacol™ is registered in over 55 countries as Asacol™ and as Octasa™, Fivasa™, Lixacol™, Asacolon™ in the United Kingdom, France, Spain and Ireland, respectively. The rights to Asacol, including the rights to the trademark, are owned by Tillotts Pharma AG in various countries except for the following: Switzerland, USA, United Kingdom, Canada, Italy, Belgium, the Netherlands and Luxembourg.
Detailed description
This is a Phase 3, randomised, double-blind, active-controlled, multi-centre, non-inferiority trial evaluating the safety and efficacy of 3.2 g of TP05/day compared to 3.2 g/day of Asacol™ with an open label extension to assess the long-term safety and tolerability of TP05 administered over a 26 week period. A total of 817 subjects with mildly to moderately active UC were evaluated. Eligible subjects were randomly assigned in a 1:1 ratio to receive 3.2 g/day of TP05 (administered once daily(OD)) or 3.2 g/day of Asacol™. The primary efficacy outcome was assessed at Week 8. All subjects who respond to TP05/Asacol™ (response or remission) continued receiving blinded study treatment for up to 12 weeks. After that, subjects could enroll in an Open Label Extension (OLE) for 26 weeks duration to receive TP05. Subjects failing to respond to study drug at the Week 8 visit could enroll in the OLE at week 8 and received 4.8 g/day of TP05.
Interventions
DRUGTP05
3.2g/day once daily for 12 weeks (blinded), 1.6g/d - 4.8g/d up to week 38 (open label)
DRUGAsacol 400 mg
3.2g/d twice daily for 12 weeks (blinded), switch to 1.6g/ - 4.8g/d TP05 up to week 38 (open label)
Sponsors
Tillotts Pharma AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Induction phase - Main criteria for inclusion include: 1. Male or non-pregnant, non-lactating females, 18 years of age or older. Females of child bearing potential must have a negative serum pregnancy test prior to randomisation, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal \[defined as a minimum of one year since the last menstrual period\]). 2. Documented diagnosis of UC with disease extending at least 15 cm from the anal verge. 3. Active UC defined by: * a. Mayo score of ≥ 5 * b. Sigmoidoscopy component score ≥ 2 confirmed by central review and * c. Rectal bleeding component score ≥ 1 4. Ability of the subject to participate fully in all aspects of this clinical trial. 5. Written informed consent must be obtained and documented. Induction Phase - Main criteria for exclusion include: Subjects who exhibit any of the following conditions are to be excluded from the study: (1) Severe UC defined by the following criteria: 6 bloody stools daily with one or more of the following: * a. oral temperature \> 37.8 degrees C or \> 100.0 degrees F * b. pulse \> 90 beats/min * c. haemoglobin \< 10 g/dL (2) Treatment with oral mesalamine at a dose of \> 2.4 g/day within 4 weeks prior to randomisation. (3) Treatment with topical therapy (mesalamine or corticosteroids) within 2 weeks prior to randomisation (4) Treatment with systemic or rectal steroids within 4 weeks prior to randomisation. (5) Treatment with immunosuppressants within 6 weeks prior to randomisation. (6) Treatment with infliximab or other biologics within 3 months prior to randomisation. (7) Treatment with antibiotics within 7 days prior to randomisation. (8) Treatment with probiotics within 7 days prior to randomisation. (9) Treatment with anti-diarrhoeal treatment within 7 days prior to randomisation. (10) Treatment with nicotine patch within 7 days prior to randomisation. (11) Received any investigational drug within 30 days prior to randomisation. (12) History of colectomy or partial colectomy. (13) History of definite dysplasia in colonic biopsies. (14) Crohn's disease. (15) Immediate or significant risk of toxic megacolon. (16) Known bleeding disorders. (17) Hypersensitivity to salicylates, aspirin, sulfasalazine or mesalazine. (18) Serum creatinine \> 1.5 times the upper limit of the normal range. (19) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin or alkaline phosphatase \> 2 times the upper limit of the normal range. (20) Serious underlying disease other than UC which in the opinion of the investigator may interfere with the subject's ability to fully participate in the study. (21) History of alcohol or drug abuse which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures. (22) Stools positive for Clostridium difficile toxin. (23) Pregnant or lactating women. (24) Prior enrolment in the study. OLE - Main criteria for inclusion include: 1. Attendance at the Week 8 visit and completion of disease activity assessments prior to enrolment in OLE at Week 12 (responders or remitters) or Week 8 (non-responders). 2. At least 75% compliance with study medication in the induction phase. OLE - Main criteria for exclusion include: (1) Withdrawal from the induction phase prior to the Week 8 visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Period 1: Clinical and Endoscopic Remission | Week 8 | Mayo Score of \<= 2 points with no individual sub-score \> 1 |
| Period 2: Clinical Response, Open-Label Extended Induction | Week 16 | A decrease in the PMCS of ≥ 2 points and ≥ 30% from baseline, with a decrease in the rectal bleeding sub-score of ≥ 1 point or absolute rectal bleeding sub-score of 1 or 0. |
| Period 3: Clinical Remission | Week 38 | Clinical Remission was defined as a score of 0 points for both stool frequency and rectal bleeding on the Partial Mayo Clinic Score (PMCS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Period 1: Rectal Bleeding Sub-score of 0 | Week 8 | Rectal bleeding sub-score of 0 was defined as a sub score on the rectal bleeding component of the Mayo score |
| Period 1: Clinical and Endoscopic Response | Week 8 | Clinical and Endoscopic Response was defined as a decrease in the Mayo score of ≥3 points from baseline and a reduction of ≥ 30% from baseline with either an accompanying decrease in the rectal bleeding sub-score of at least 1 point or an absolute rectal bleeding sub-score of 0 or 1 at the Week 8 visit. If a subject withdrew from the study prior to Week 8 or their response status was not evaluable due to incomplete and/or invalid data, the subject was considered a non-responder. |
| Period 1: Clinical Response | Week 12 | A decrease in the PMCS of ≥ 2 points and ≥ 30% from baseline, with a decrease in the rectal bleeding sub-score of ≥ 1 point or absolute rectal bleeding sub-score of 1 or 0. |
| Period 1: Rectal Bleeding Score of 0 | Week 12 | Rectal bleeding sub-score of 0 was defined as a sub score on the rectal bleeding component of the Mayo score |
| Period 1: Clinical Remission at Both Week 8 and 12 | Week 8 and week 12 | Clinical Remission was defined as a score of 0 points for both stool frequency and rectal bleeding on the Partial Mayo Clinic Score (PMCS) |
| Period 1: Clinical Response at Both Week 8 and Week 12 | Week 8 and Week 12 | A decrease in the Partial Mayo Score of ≥ 2 points and ≥ 30% from baseline, with a decrease in the rectal bleeding sub-score of ≥ 1 point or absolute rectal bleeding sub-score of 1 or 0. |
| Period 1: Change in Mayo Score From Baseline | Baseline and Week 8 | Between-Group Difference of Mayo Score, Change from Baseline The changes from baseline to week 8 values in Mayo scores are compared between the two treatment groups. The Mayo scoring system is a well-established tool for assessing UC disease activity. The Mayo score is the sum of 4 component sub-scores, each scored on a scale ranging from 0 representing no pathology to 3 for severe disease. The 4 component sub-scores consist of, 1) stool frequency, 2) rectal bleeding, 3) flexible sigmoidoscopy scores, and 4) physician's global assessment. A Mayo score of 0 indicates no pathology and a score of 12, severe disease. Change from Baseline is calculated Baseline-score minus week 8-score. A larger change in Mayo score from baseline when patients experienced acute disease, indicates improvement and treatment success. |
| Period 3: Clinical Response | Week 38 | A decrease in the PMCS of ≥ 2 points and ≥ 30% from baseline, with a decrease in the rectal bleeding sub-score of ≥ 1 point or absolute rectal bleeding sub-score of 1 or 0. |
| Period 1: Change in Partial Mayo Score From Baseline | Baseline and Week 8 | Between-Group Difference of Partial Mayo Score, Change from Baseline to Week 8 The Partial Mayo Score is the sum of the component sub-scores, 1) stool frequency, 2) rectal bleeding and 3) physician's global assessment. A partial Mayo Score of 0 indicates no disease and a maximum score of 9 indicates severe symptoms. Change from Baseline is calculated Baseline-score minus week 8-score. A larger change in Partial Mayo Score from Baseline where patients experienced acute disease, indicates improvement and treatment success. |
| Period 1: Change in Stool Frequency Score | Baseline and Week 8 | Between-Group Difference of Stool Frequency Score, Change from Baseline The changes from baseline to week 8 values in stool frequency will be compared between the two treatment groups. Values for stool frequency range between 0 and 3. A value of 0 indicates normal stool frequency, a value of 3 indicates 5 or more stools than normal. Change from Baseline is calculated Baseline-score minus week 8-score. A large difference between week 8 values and baselines indicates treatment success. |
| Period 1: Change in Rectal Bleeding Score From Baseline | Baseline and Week 8 | Between-Group Difference of Rectal Bleeding Score, Change from Baseline The changes from baseline to week 8 values in rectal bleeding scores will be compared between the two treatment groups. A value of 0 indicates no rectal bleeding, a value of 3 indicates only blood is passing. Change from Baseline is calculated Baseline-score minus week 8-score. A large difference at week 8 compared to baseline is indicative of treatment success. |
| Period 1: Change in Physician Global Assessment Score From Baseline | Baseline and Week 8 | Between-Group Difference of Physician Global Assessment Score, Change from Baseline. The changes from baseline to week 8 values in the Physician Global Assessment score will be compared between the two treatment groups. A value of 0 means no pathology and a value of 3 means severe disease. Change from Baseline is calculated Baseline-score minus week 8-score. A large difference between baseline to week 8 indicates treatment success. |
| Period 1: Change in Endoscopic Score From Baseline | Baseline and Week 8 | Between-Group Difference of Endoscopic Score, Change from Baseline. The changes from baseline to week 8 values in sigmoidoscopic (mucosal) appearance scores will be compared between the two treatment groups. A value of 0 in the endoscopic score means normal or inactive disease and a value of 3 means severe disease. Change from Baseline is calculated Baseline-score minus week 8-score. A large difference between baseline to week 8 indicates treatment success. |
| Period 1: Endoscopic Remission | Week 8 | Endoscopic remission was defined as a Mayo endoscopy subscore of 0 |
| Period 2: Rectal Bleeding Sub-score of 0 | Week 16 | Percentage of patients achieving the endpoint rectal bleeding sub-score of 0 |
| Period 2: Stool Frequency 0 | Week 16 | Percentage of patients achieving the endpoint stool frequency sub-score of 0 |
| Period 2: Urgency | Week 16 | Percentage of patients achieving an Urgency Score of 0. A score of 0 indicates no urgency reported in any of the three days prior to the visit at week 16. A score of 1 indicates urgency reported in any of the three days prior to the visits. |
| Period 2: UC-Related Complications | Week 16 | Percentage of Patients Experiencing Complications related to UC |
| Period 3: Clinical and Endoscopic Remission | Week 38 | Mayo Score of \<= 2 points with no individual sub-score \> 1 |
| Period 3: Clinical and Endoscopic Response | Week 38 | Both has to be achieved, Clinical and Endoscopic Response which is defined by a decrease from baseline in the Mayo score of ≥ 3 points and \> 30% of the baseline score, with an accompanying decrease in the rectal bleeding sub-score of ≥ 1 point or an absolute rectal bleeding sub-score of 0 or 1. |
| Period 3: Endoscopic Remission | Week 38 | Percentage of each dose group achieving an endoscopy sub score of 0 |
| Period 3: Endoscopic Response | Week 38 | Endoscopic response was define as a reduction in the Mayo endoscopic sub score of at least one. |
| Period 3: Rectal Bleeding Sub Score of 0 | Week 38 | Percentage of each dose group achieving the endpoint rectal bleeding subscore 0 |
| Period 3: Stool Frequency Sub-score 0 | Week 38 | Patients achieving a Stool Frequency sub-score of 0 |
| Period 3: No Urgency | Week 38 | No urgency is a score of 0 and indicates that patients did not report urgency during any of the three days prior to the visit at week 38. A score of 1 indicates that urgency was reported during any of these three days. |
| Period 3: UC-Related Complications | Week 38 | Percentage of Patients with Complications related to UC |
| Period 2: Clinical Remission | Week 16 | Clinical Remission was defined as a score of 0 points for both stool frequency and rectal bleeding on the Partial Mayo Clinic Score (PMCS) |
| Period 1: Endoscopic Response | Week 8 | Endoscopic response was define as a reduction in the Mayo endoscopic sub score of at least one. |
| Period 1: Clinical Remission | Week 8 | Clinical Remission was defined as a score of 0 points for both stool frequency and rectal bleeding on the Partial Mayo Clinic Score (PMCS) |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TP05 (Mesalazine) 3.2 gram/day (g/d) once daily (OD) for 12 weeks (blinded), | 409 |
| Asacol (Mesalazine, Tillotts Pharma AG) 3.2g/d twice daily for 12 weeks (blinded), | 408 |
| Total | 817 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Double-Blind Induction | Adverse Event | 20 | 18 | 0 | 0 | 0 | 0 |
| Double-Blind Induction | non-compliance, | 7 | 7 | 0 | 0 | 0 | 0 |
| Double-Blind Induction | Physician Decision | 2 | 3 | 0 | 0 | 0 | 0 |
| Double-Blind Induction | Withdrawal by Subject | 10 | 13 | 0 | 0 | 0 | 0 |
| Extended Induction, Open-Label | Adverse Event | 0 | 0 | 17 | 0 | 0 | 0 |
| Extended Induction, Open-Label | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 |
| Extended Induction, Open-Label | Withdrawal by Subject | 0 | 0 | 5 | 0 | 0 | 0 |
| Maintenance, Open-Label | Adverse Event | 0 | 0 | 0 | 3 | 9 | 14 |
| Maintenance, Open-Label | Other | 0 | 0 | 0 | 2 | 6 | 2 |
| Maintenance, Open-Label | Withdrawal by Subject | 0 | 0 | 0 | 1 | 6 | 2 |
Baseline characteristics
| Characteristic | TP05 (Mesalazine) | Asacol (Mesalazine, Tillotts Pharma AG) | Total |
|---|---|---|---|
| Age, Continuous | 43.97 years STANDARD_DEVIATION 14.54 | 43.3 years STANDARD_DEVIATION 14.11 | 43.5 years STANDARD_DEVIATION 14.32 |
| Mayo Score | 7.7 units on a scale STANDARD_DEVIATION 1.3 | 7.6 units on a scale STANDARD_DEVIATION 1.3 | 7.7 units on a scale STANDARD_DEVIATION 1.3 |
| Partial Mayo Clinic Score | 5.5 units on a scale STANDARD_DEVIATION 1.1 | 5.3 units on a scale STANDARD_DEVIATION 1.1 | 5.4 units on a scale STANDARD_DEVIATION 1.1 |
| Race/Ethnicity, Customized Asian or Pacific Islander | 7 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Mixed/Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Available | 23 Participants | 17 Participants | 40 Participants |
| Race/Ethnicity, Customized White | 378 Participants | 386 Participants | 764 Participants |
| Region of Enrollment Belarus | 47 participants | 49 participants | 96 participants |
| Region of Enrollment Belgium | 9 participants | 8 participants | 17 participants |
| Region of Enrollment Bulgaria | 15 participants | 15 participants | 30 participants |
| Region of Enrollment Canada | 15 participants | 17 participants | 32 participants |
| Region of Enrollment Czech Republic | 20 participants | 18 participants | 38 participants |
| Region of Enrollment Denmark | 20 participants | 16 participants | 36 participants |
| Region of Enrollment Finland | 2 participants | 1 participants | 3 participants |
| Region of Enrollment France | 23 participants | 16 participants | 39 participants |
| Region of Enrollment Hungary | 17 participants | 11 participants | 28 participants |
| Region of Enrollment Ireland | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Latvia | 22 participants | 22 participants | 44 participants |
| Region of Enrollment Lithuania | 26 participants | 28 participants | 54 participants |
| Region of Enrollment Norway | 4 participants | 5 participants | 9 participants |
| Region of Enrollment Poland | 44 participants | 48 participants | 92 participants |
| Region of Enrollment Romania | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Russian Federation | 51 participants | 50 participants | 101 participants |
| Region of Enrollment Serbia | 18 participants | 18 participants | 36 participants |
| Region of Enrollment Slovakia | 2 participants | 3 participants | 5 participants |
| Region of Enrollment Spain | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Sweden | 1 participants | 2 participants | 3 participants |
| Region of Enrollment Ukraine | 59 participants | 71 participants | 130 participants |
| Region of Enrollment United Kingdom | 11 participants | 7 participants | 18 participants |
| Sex: Female, Male Female | 171 Participants | 178 Participants | 349 Participants |
| Sex: Female, Male Male | 238 Participants | 230 Participants | 468 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 58 / 409 | 75 / 408 | 0 / 243 | 26 / 409 | 22 / 408 |
| serious Total, serious adverse events | 24 / 409 | 18 / 408 | 3 / 243 | 9 / 409 | 7 / 408 |
Outcome results
Primary
Period 1: Clinical and Endoscopic Remission
Mayo Score of \<= 2 points with no individual sub-score \> 1
Time frame: Week 8
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Clinical and Endoscopic Remission | 87 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Clinical and Endoscopic Remission | 95 Participants |
Comparison: If the lower limit of the confidence interval was no less than -10% it would be concluded that the test product is non-inferior to the comparator.p-value: 0.00595% CI: [-8.1, 3.8]Non-inferiority
Primary
Period 2: Clinical Response, Open-Label Extended Induction
A decrease in the PMCS of ≥ 2 points and ≥ 30% from baseline, with a decrease in the rectal bleeding sub-score of ≥ 1 point or absolute rectal bleeding sub-score of 1 or 0.
Time frame: Week 16
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 2: Clinical Response, Open-Label Extended Induction | 183 Participants |
95% CI: [69.4, 80.6]
Primary
Period 3: Clinical Remission
Clinical Remission was defined as a score of 0 points for both stool frequency and rectal bleeding on the Partial Mayo Clinic Score (PMCS)
Time frame: Week 38
Population: Intent to Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TP05 (Mesalazine) | Period 3: Clinical Remission | 70.3 percentage of participant |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 3: Clinical Remission | 33.9 percentage of participant |
| 4.8g/Day Maintenance Open-Label | Period 3: Clinical Remission | 30.7 percentage of participant |
Secondary
Period 1: Change in Endoscopic Score From Baseline
Between-Group Difference of Endoscopic Score, Change from Baseline. The changes from baseline to week 8 values in sigmoidoscopic (mucosal) appearance scores will be compared between the two treatment groups. A value of 0 in the endoscopic score means normal or inactive disease and a value of 3 means severe disease. Change from Baseline is calculated Baseline-score minus week 8-score. A large difference between baseline to week 8 indicates treatment success.
Time frame: Baseline and Week 8
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TP05 (Mesalazine) | Period 1: Change in Endoscopic Score From Baseline | 0.5 units on a scale | Standard Deviation 0.9 |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Change in Endoscopic Score From Baseline | 0.6 units on a scale | Standard Deviation 0.8 |
p-value: 0.09995% CI: [-0.2, 0]t-test, 2 sided
Secondary
Period 1: Change in Mayo Score From Baseline
Between-Group Difference of Mayo Score, Change from Baseline The changes from baseline to week 8 values in Mayo scores are compared between the two treatment groups. The Mayo scoring system is a well-established tool for assessing UC disease activity. The Mayo score is the sum of 4 component sub-scores, each scored on a scale ranging from 0 representing no pathology to 3 for severe disease. The 4 component sub-scores consist of, 1) stool frequency, 2) rectal bleeding, 3) flexible sigmoidoscopy scores, and 4) physician's global assessment. A Mayo score of 0 indicates no pathology and a score of 12, severe disease. Change from Baseline is calculated Baseline-score minus week 8-score. A larger change in Mayo score from baseline when patients experienced acute disease, indicates improvement and treatment success.
Time frame: Baseline and Week 8
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TP05 (Mesalazine) | Period 1: Change in Mayo Score From Baseline | 3.1 units on a scale | Standard Deviation 2.7 |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Change in Mayo Score From Baseline | 3.2 units on a scale | Standard Deviation 2.6 |
p-value: 0.55795% CI: [-0.5, 0.3]t-test, 2 sided
Secondary
Period 1: Change in Partial Mayo Score From Baseline
Between-Group Difference of Partial Mayo Score, Change from Baseline to Week 8 The Partial Mayo Score is the sum of the component sub-scores, 1) stool frequency, 2) rectal bleeding and 3) physician's global assessment. A partial Mayo Score of 0 indicates no disease and a maximum score of 9 indicates severe symptoms. Change from Baseline is calculated Baseline-score minus week 8-score. A larger change in Partial Mayo Score from Baseline where patients experienced acute disease, indicates improvement and treatment success.
Time frame: Baseline and Week 8
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TP05 (Mesalazine) | Period 1: Change in Partial Mayo Score From Baseline | 2.5 units on a scale | Standard Deviation 2.2 |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Change in Partial Mayo Score From Baseline | 2.5 units on a scale | Standard Deviation 2.2 |
p-value: 0.98795% CI: [-0.3, 0.3]t-test, 2 sided
Secondary
Period 1: Change in Physician Global Assessment Score From Baseline
Between-Group Difference of Physician Global Assessment Score, Change from Baseline. The changes from baseline to week 8 values in the Physician Global Assessment score will be compared between the two treatment groups. A value of 0 means no pathology and a value of 3 means severe disease. Change from Baseline is calculated Baseline-score minus week 8-score. A large difference between baseline to week 8 indicates treatment success.
Time frame: Baseline and Week 8
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TP05 (Mesalazine) | Period 1: Change in Physician Global Assessment Score From Baseline | 0.6 units on a scale | Standard Deviation 0.8 |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Change in Physician Global Assessment Score From Baseline | 0.7 units on a scale | Standard Deviation 0.8 |
p-value: 0.35795% CI: [-0.2, 0.1]t-test, 2 sided
Secondary
Period 1: Change in Rectal Bleeding Score From Baseline
Between-Group Difference of Rectal Bleeding Score, Change from Baseline The changes from baseline to week 8 values in rectal bleeding scores will be compared between the two treatment groups. A value of 0 indicates no rectal bleeding, a value of 3 indicates only blood is passing. Change from Baseline is calculated Baseline-score minus week 8-score. A large difference at week 8 compared to baseline is indicative of treatment success.
Time frame: Baseline and Week 8
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TP05 (Mesalazine) | Period 1: Change in Rectal Bleeding Score From Baseline | 0.9 units on a scale | Standard Deviation 0.8 |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Change in Rectal Bleeding Score From Baseline | 1.0 units on a scale | Standard Deviation 0.8 |
p-value: 0.93795% CI: [-0.1, 0.1]t-test, 2 sided
Secondary
Period 1: Change in Stool Frequency Score
Between-Group Difference of Stool Frequency Score, Change from Baseline The changes from baseline to week 8 values in stool frequency will be compared between the two treatment groups. Values for stool frequency range between 0 and 3. A value of 0 indicates normal stool frequency, a value of 3 indicates 5 or more stools than normal. Change from Baseline is calculated Baseline-score minus week 8-score. A large difference between week 8 values and baselines indicates treatment success.
Time frame: Baseline and Week 8
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TP05 (Mesalazine) | Period 1: Change in Stool Frequency Score | 0.9 units on a scale | Standard Deviation 1.1 |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Change in Stool Frequency Score | 0.9 units on a scale | Standard Deviation 1.1 |
p-value: 0.45595% CI: [-0.1, 0.2]t-test, 2 sided
Secondary
Period 1: Clinical and Endoscopic Response
Clinical and Endoscopic Response was defined as a decrease in the Mayo score of ≥3 points from baseline and a reduction of ≥ 30% from baseline with either an accompanying decrease in the rectal bleeding sub-score of at least 1 point or an absolute rectal bleeding sub-score of 0 or 1 at the Week 8 visit. If a subject withdrew from the study prior to Week 8 or their response status was not evaluable due to incomplete and/or invalid data, the subject was considered a non-responder.
Time frame: Week 8
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Clinical and Endoscopic Response | 221 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Clinical and Endoscopic Response | 236 Participants |
p-value: 0.04895% CI: [-11, 2.7]Non-inferiority
Secondary
Period 1: Clinical Remission
Clinical Remission was defined as a score of 0 points for both stool frequency and rectal bleeding on the Partial Mayo Clinic Score (PMCS)
Time frame: Week 12
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Clinical Remission | 93 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Clinical Remission | 113 Participants |
p-value: 0.06895% CI: [-11.5, 0.9]Non-inferiority
Secondary
Period 1: Clinical Remission
Clinical Remission was defined as a score of 0 points for both stool frequency and rectal bleeding on the Partial Mayo Clinic Score (PMCS)
Time frame: Week 8
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Clinical Remission | 92 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Clinical Remission | 110 Participants |
p-value: 0.04895% CI: [-10.9, 1.4]Non-inferiority
Secondary
Period 1: Clinical Remission at Both Week 8 and 12
Clinical Remission was defined as a score of 0 points for both stool frequency and rectal bleeding on the Partial Mayo Clinic Score (PMCS)
Time frame: Week 8 and week 12
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Clinical Remission at Both Week 8 and 12 | 66 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Clinical Remission at Both Week 8 and 12 | 80 Participants |
p-value: 0.01395% CI: [-9.2, 1.8]Non-inferiority
Secondary
Period 1: Clinical Response
A decrease in the PMCS of ≥ 2 points and ≥ 30% from baseline, with a decrease in the rectal bleeding sub-score of ≥ 1 point or absolute rectal bleeding sub-score of 1 or 0.
Time frame: Week 12
Population: Per protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Clinical Response | 223 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Clinical Response | 233 Participants |
p-value: 0.02195% CI: [-9.8, 4]Non-inferiortiy
Secondary
Period 1: Clinical Response at Both Week 8 and Week 12
A decrease in the Partial Mayo Score of ≥ 2 points and ≥ 30% from baseline, with a decrease in the rectal bleeding sub-score of ≥ 1 point or absolute rectal bleeding sub-score of 1 or 0.
Time frame: Week 8 and Week 12
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Clinical Response at Both Week 8 and Week 12 | 216 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Clinical Response at Both Week 8 and Week 12 | 230 Participants |
p-value: 0.04295% CI: [-10.8, 3]Non-inferiority
Secondary
Period 1: Endoscopic Remission
Endoscopic remission was defined as a Mayo endoscopy subscore of 0
Time frame: Week 8
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Endoscopic Remission | 36 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Endoscopic Remission | 44 Participants |
p-value: <0.00195% CI: [-6.5, 2.2]Non-inferiority
Secondary
Period 1: Endoscopic Response
Endoscopic response was define as a reduction in the Mayo endoscopic sub score of at least one.
Time frame: Week 8
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Endoscopic Response | 185 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Endoscopic Response | 196 Participants |
p-value: 0.02695% CI: [-10.1, 3.9]Non-inferiority
Secondary
Period 1: Rectal Bleeding Score of 0
Rectal bleeding sub-score of 0 was defined as a sub score on the rectal bleeding component of the Mayo score
Time frame: Week 12
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Rectal Bleeding Score of 0 | 193 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Rectal Bleeding Score of 0 | 205 Participants |
p-value: 0.03195% CI: [-10.3, 3.7]Non-inferiortiy
Secondary
Period 1: Rectal Bleeding Sub-score of 0
Rectal bleeding sub-score of 0 was defined as a sub score on the rectal bleeding component of the Mayo score
Time frame: Week 8
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 1: Rectal Bleeding Sub-score of 0 | 212 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 1: Rectal Bleeding Sub-score of 0 | 226 Participants |
p-value: 0.04295% CI: [-10.8, 3.1]Non-inferiortiy
Secondary
Period 2: Clinical Remission
Clinical Remission was defined as a score of 0 points for both stool frequency and rectal bleeding on the Partial Mayo Clinic Score (PMCS)
Time frame: Week 16
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 2: Clinical Remission | 53 Participants |
95% CI: [16.8, 27.5]
Secondary
Period 2: Rectal Bleeding Sub-score of 0
Percentage of patients achieving the endpoint rectal bleeding sub-score of 0
Time frame: Week 16
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 2: Rectal Bleeding Sub-score of 0 | 146 Participants |
95% CI: [53.6, 66.3]
Secondary
Period 2: Stool Frequency 0
Percentage of patients achieving the endpoint stool frequency sub-score of 0
Time frame: Week 16
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 2: Stool Frequency 0 | 64 Participants |
95% CI: [20.9, 32.3]
Secondary
Period 2: UC-Related Complications
Percentage of Patients Experiencing Complications related to UC
Time frame: Week 16
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 2: UC-Related Complications | 0.0 Participants |
95% CI: [0, 1.5]
Secondary
Period 2: Urgency
Percentage of patients achieving an Urgency Score of 0. A score of 0 indicates no urgency reported in any of the three days prior to the visit at week 16. A score of 1 indicates urgency reported in any of the three days prior to the visits.
Time frame: Week 16
Population: Indent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 2: Urgency | 109 Participants |
95% CI: [38.5, 51.3]
Secondary
Period 3: Clinical and Endoscopic Remission
Mayo Score of \<= 2 points with no individual sub-score \> 1
Time frame: Week 38
Population: Intent to Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TP05 (Mesalazine) | Period 3: Clinical and Endoscopic Remission | 65.8 percentage of participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 3: Clinical and Endoscopic Remission | 39.4 percentage of participants |
| 4.8g/Day Maintenance Open-Label | Period 3: Clinical and Endoscopic Remission | 29.6 percentage of participants |
Secondary
Period 3: Clinical and Endoscopic Response
Both has to be achieved, Clinical and Endoscopic Response which is defined by a decrease from baseline in the Mayo score of ≥ 3 points and \> 30% of the baseline score, with an accompanying decrease in the rectal bleeding sub-score of ≥ 1 point or an absolute rectal bleeding sub-score of 0 or 1.
Time frame: Week 38
Population: Intent to Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TP05 (Mesalazine) | Period 3: Clinical and Endoscopic Response | 89.6 percentage of participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 3: Clinical and Endoscopic Response | 78.1 percentage of participants |
| 4.8g/Day Maintenance Open-Label | Period 3: Clinical and Endoscopic Response | 69.3 percentage of participants |
Secondary
Period 3: Clinical Response
A decrease in the PMCS of ≥ 2 points and ≥ 30% from baseline, with a decrease in the rectal bleeding sub-score of ≥ 1 point or absolute rectal bleeding sub-score of 1 or 0.
Time frame: Week 38
Population: Intent to Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TP05 (Mesalazine) | Period 3: Clinical Response | 94.1 percentage of participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 3: Clinical Response | 83.9 percentage of participants |
| 4.8g/Day Maintenance Open-Label | Period 3: Clinical Response | 78.4 percentage of participants |
Secondary
Period 3: Endoscopic Remission
Percentage of each dose group achieving an endoscopy sub score of 0
Time frame: Week 38
Population: Intent to Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TP05 (Mesalazine) | Period 3: Endoscopic Remission | 37.6 percentage of participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 3: Endoscopic Remission | 32.4 percentage of participants |
| 4.8g/Day Maintenance Open-Label | Period 3: Endoscopic Remission | 13.6 percentage of participants |
Secondary
Period 3: Endoscopic Response
Endoscopic response was define as a reduction in the Mayo endoscopic sub score of at least one.
Time frame: Week 38
Population: Intent to Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TP05 (Mesalazine) | Period 3: Endoscopic Response | 73.8 percentage of participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 3: Endoscopic Response | 58.8 percentage of participants |
| 4.8g/Day Maintenance Open-Label | Period 3: Endoscopic Response | 53.3 percentage of participants |
Secondary
Period 3: No Urgency
No urgency is a score of 0 and indicates that patients did not report urgency during any of the three days prior to the visit at week 38. A score of 1 indicates that urgency was reported during any of these three days.
Time frame: Week 38
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 3: No Urgency | 161 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 3: No Urgency | 173 Participants |
| 4.8g/Day Maintenance Open-Label | Period 3: No Urgency | 109 Participants |
Secondary
Period 3: Rectal Bleeding Sub Score of 0
Percentage of each dose group achieving the endpoint rectal bleeding subscore 0
Time frame: Week 38
Population: Intent to Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TP05 (Mesalazine) | Period 3: Rectal Bleeding Sub Score of 0 | 88.1 percentage of participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 3: Rectal Bleeding Sub Score of 0 | 76.3 percentage of participants |
| 4.8g/Day Maintenance Open-Label | Period 3: Rectal Bleeding Sub Score of 0 | 74.9 percentage of participants |
Secondary
Period 3: Stool Frequency Sub-score 0
Patients achieving a Stool Frequency sub-score of 0
Time frame: Week 38
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 3: Stool Frequency Sub-score 0 | 148 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 3: Stool Frequency Sub-score 0 | 101 Participants |
| 4.8g/Day Maintenance Open-Label | Period 3: Stool Frequency Sub-score 0 | 66 Participants |
Secondary
Period 3: UC-Related Complications
Percentage of Patients with Complications related to UC
Time frame: Week 38
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TP05 (Mesalazine) | Period 3: UC-Related Complications | 3 Participants |
| Asacol (Mesalazine, Tillotts Pharma AG) | Period 3: UC-Related Complications | 2 Participants |
| 4.8g/Day Maintenance Open-Label | Period 3: UC-Related Complications | 1 Participants |