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The purpose of this research study was to compare the medication TP05 to the medication Asacolâ„¢ 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) Asacolâ„¢(1).
(1)The trademark Asacolâ„¢ is registered in over 55 countries as Asacolâ„¢ and as Octasaâ„¢, Fivasaâ„¢, Lixacolâ„¢, Asacolonâ„¢ 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.
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 Asacolâ„¢ 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 Asacolâ„¢. The primary efficacy outcome was assessed at Week 8. All subjects who respond to TP05/Asacolâ„¢ (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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TP05 (Mesalazine) 1600mg | Experimental | week 1 - week 12 (blinded), week 13 - week 38 (OpenLabel) |
|
| Asacol 400 mg (Tillotts Pharma) | Active Comparator | week 1 - week 12 (blinded), switch to TP05 for weeks 13-38 (open label) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TP05 | Drug | 3.2g/day once daily for 12 weeks (blinded), 1.6g/d - 4.8g/d up to week 38 (open label) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Period 1: Clinical and Endoscopic Remission | Mayo Score of <= 2 points with no individual sub-score > 1 | Week 8 |
| 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. | Week 16 |
| 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) | Week 38 |
| Measure | Description | Time Frame |
|---|---|---|
| Period 1: Endoscopic Remission | Endoscopic remission was defined as a Mayo endoscopy subscore of 0 | Week 8 |
| Period 1: Endoscopic Response | Endoscopic response was define as a reduction in the Mayo endoscopic sub score of at least one. |
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Induction phase - Main criteria for inclusion include:
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]).
Documented diagnosis of UC with disease extending at least 15 cm from the anal verge.
Active UC defined by:
Ability of the subject to participate fully in all aspects of this clinical trial.
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:
OLE - Main criteria for exclusion include:
(1) Withdrawal from the induction phase prior to the Week 8 visit.
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| Name | Affiliation | Role |
|---|---|---|
| Geert R D'Haens, MD, PhD | Alimentiv Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tillotts Pharma AG | Rheinfelden | Baslerstrasse 15 | 4310 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33279779 | Derived | Ma C, Jeyarajah J, Guizzetti L, Parker CE, Singh S, Dulai PS, D'Haens GR, Sandborn WJ, Feagan BG, Jairath V. Modeling Endoscopic Improvement after Induction Treatment With Mesalamine in Patients With Mild-to-Moderate Ulcerative Colitis. Clin Gastroenterol Hepatol. 2022 Feb;20(2):447-454.e1. doi: 10.1016/j.cgh.2020.11.040. Epub 2020 Dec 3. | |
| 31546056 |
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| ID | Title | Description |
|---|---|---|
| FG000 | TP05 (Mesalazine) 1600 mg | 3.2g/day once daily (OD) for 12 weeks (blinded), |
| FG001 | Asacol (Mesalazine 400 mg) | 3.2g/d twice daily for 12 weeks (blinded), |
| FG002 | Extended Induction | Non-responders at week 8 of the induction phase were taken out of the double-blind phase and treated with TP05 4.8g/day OD for another 8 weeks |
| FG003 | 1.6g TP05 (1600 mg) /Day Maintenance Open-Label | Remitters at week 12 of the induction phase received a daily dose of 1.6g OD in the maintenance phase open-label. |
| FG004 | 3.2g TP05 (1600 mg) /Day Maintenance Open-Label | Responders at week 12 of the induction phase remained on a daily dose of 3.2 g OD in the maintenance phase open-label. |
| FG005 | 4.8g TP05 (1600 mg) /Day Maintenance Open-Label | Non-responders at week 12 of the double-blind induction phase as well as non-responders at week 8 of the induction phase who responded after a second 8 weeks of extended induction treatments, were enrolled into the maintenance phase and remained on a daily dose of 4.8g OD. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Double-Blind Induction |
|
| ||||||||||||||||||
| Extended Induction, Open-Label |
| |||||||||||||||||||
| Maintenance, Open-Label |
|
Safety Population (SAF)/Intent to Treat (ITT)
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| ID | Title | Description |
|---|---|---|
| BG000 | TP05 (Mesalazine) | 3.2 gram/day (g/d) once daily (OD) for 12 weeks (blinded), |
| BG001 | Asacol (Mesalazine, Tillotts Pharma AG) | 3.2g/d twice daily for 12 weeks (blinded), |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Period 1: Clinical and Endoscopic Remission | Mayo Score of <= 2 points with no individual sub-score > 1 | Per Protocol | Posted | Count of Participants | Participants | Week 8 |
|
|
2 years, 11 months
Adverse Events (AEs) were analysed for each arm of the double-blind Induction Phase, for the Open-Label Extended Induction Phase and combined for the double-blind Induction Phase and the Open-Label Maintenance Phase but not for the Open-Label Maintenance Phase separately. In adding safety results of the Maintenance Phase to the safety results of the Induction Phase ensured that one occurence of an AE was counted as one AE and not as two when AEs continued from one phase to the other.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TP05/TP05 | Double-blind Induction Phase: TP05, and Open-Label Maintenance Phase: TP05 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deterioration ulcerative colities | Gastrointestinal disorders | MedDra (18.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Worsening of UC | Gastrointestinal disorders | MedDra 18 | Systematic Assessment | Symptoms of active ulcerative colitis |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Robert Hofmann, MD PhD | Tillotts Pharma AG | +4161 935 27 14 | robert.hofmann@tillotts.com |
| ID | Term |
|---|---|
| D019804 | Mesalamine |
| ID | Term |
|---|---|
| D062368 | meta-Aminobenzoates |
| D062365 | Aminobenzoates |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
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Double-blind
| Asacol 400 mg | Drug | 3.2g/d twice daily for 12 weeks (blinded), switch to 1.6g/ - 4.8g/d TP05 up to week 38 (open label) |
|
|
| Week 8 |
| 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) | Week 8 |
| 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 | Week 8 |
| 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. | Week 8 |
| 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) | Week 12 |
| 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. | Week 12 |
| 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 | Week 12 |
| 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) | Week 8 and week 12 |
| 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. | Week 8 and Week 12 |
| 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. | Baseline and Week 8 |
| 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. | Baseline and Week 8 |
| 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. | Baseline and Week 8 |
| 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. | Baseline and Week 8 |
| 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. | Baseline and Week 8 |
| 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. | Baseline and Week 8 |
| 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) | Week 16 |
| Period 2: Rectal Bleeding Sub-score of 0 | Percentage of patients achieving the endpoint rectal bleeding sub-score of 0 | Week 16 |
| Period 2: Stool Frequency 0 | Percentage of patients achieving the endpoint stool frequency sub-score of 0 | Week 16 |
| 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. | Week 16 |
| Period 2: UC-Related Complications | Percentage of Patients Experiencing Complications related to UC | Week 16 |
| 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. | Week 38 |
| Period 3: Clinical and Endoscopic Remission | Mayo Score of <= 2 points with no individual sub-score > 1 | Week 38 |
| 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. | Week 38 |
| Period 3: Endoscopic Remission | Percentage of each dose group achieving an endoscopy sub score of 0 | Week 38 |
| Period 3: Endoscopic Response | Endoscopic response was define as a reduction in the Mayo endoscopic sub score of at least one. | Week 38 |
| Period 3: Rectal Bleeding Sub Score of 0 | Percentage of each dose group achieving the endpoint rectal bleeding subscore 0 | Week 38 |
| Period 3: Stool Frequency Sub-score 0 | Patients achieving a Stool Frequency sub-score of 0 | Week 38 |
| 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. | Week 38 |
| Period 3: UC-Related Complications | Percentage of Patients with Complications related to UC | Week 38 |
| Ma C, Sandborn WJ, D'Haens GR, Zou G, Stitt LW, Singh S, Ananthakrishnan AN, Dulai PS, Khanna R, Jairath V, Feagan BG. Discordance Between Patient-Reported Outcomes and Mucosal Inflammation in Patients With Mild to Moderate Ulcerative Colitis. Clin Gastroenterol Hepatol. 2020 Jul;18(8):1760-1768.e1. doi: 10.1016/j.cgh.2019.09.021. Epub 2019 Sep 20. |
| 28568974 | Derived | D'Haens GR, Sandborn WJ, Zou G, Stitt LW, Rutgeerts PJ, Gilgen D, Jairath V, Hindryckx P, Shackelton LM, Vandervoort MK, Parker CE, Muller C, Pai RK, Levchenko O, Marakhouski Y, Horynski M, Mikhailova E, Kharchenko N, Pimanov S, Feagan BG. Randomised non-inferiority trial: 1600 mg versus 400 mg tablets of mesalazine for the treatment of mild-to-moderate ulcerative colitis. Aliment Pharmacol Ther. 2017 Aug;46(3):292-302. doi: 10.1111/apt.14164. Epub 2017 Jun 1. |
| Withdrawal by Subject |
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| Physician Decision |
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| non-compliance, |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| Mayo Score | Mayo Score and Partial Mayo Clinic Score (PMCS): 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 ranging from 0 representing no pathology to 3 for severe disease. The 4 component sub-scores are: 1) stool frequency, 2) rectal bleeding, 3) flexible sigmoidoscopy scores, and 4) physician's global assessment. The minimum Mayo Score is 0 (no pathology) and the maximum is 12 (severe disease in all sub-scores). | Mean | Standard Deviation | units on a scale |
|
| Partial Mayo Clinic Score | Partial Mayo Clinic Score (PMCS) is the sum of the component sub-scores, excluding the endoscopic score. The 3 component sub-scores are: 1) stool frequency, 2) rectal bleeding, and 3) physician's global assessment. The minimum is 0, no pathology and the maximum is 9, severe disease in all sub-scores. | Mean | Standard Deviation | units on a scale |
|
| Participants |
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| 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. | Intent to Treat | Posted | Count of Participants | Participants | Week 16 |
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| 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) | Intent to Treat | Posted | Number | percentage of participant | Week 38 |
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| Secondary | Period 1: Endoscopic Remission | Endoscopic remission was defined as a Mayo endoscopy subscore of 0 | Per Protocol | Posted | Count of Participants | Participants | Week 8 |
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| Secondary | Period 1: Endoscopic Response | Endoscopic response was define as a reduction in the Mayo endoscopic sub score of at least one. | Per Protocol | Posted | Count of Participants | Participants | Week 8 |
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| 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) | Per Protocol | Posted | Count of Participants | Participants | Week 8 |
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| 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 | Per Protocol | Posted | Count of Participants | Participants | Week 8 |
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| 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. | Per Protocol | Posted | Count of Participants | Participants | Week 8 |
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| 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) | Per Protocol | Posted | Count of Participants | Participants | Week 12 |
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| 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. | Per protocol | Posted | Count of Participants | Participants | Week 12 |
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| 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 | Per Protocol | Posted | Count of Participants | Participants | Week 12 |
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| 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) | Per Protocol | Posted | Count of Participants | Participants | Week 8 and week 12 |
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| 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. | Per Protocol | Posted | Count of Participants | Participants | Week 8 and Week 12 |
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| 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. | Per Protocol | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 8 |
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| 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. | Per Protocol | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 8 |
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| 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. | Per Protocol | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 8 |
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| 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. | Per Protocol | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 8 |
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| 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. | Per Protocol | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 8 |
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| 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. | Per Protocol | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 8 |
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| 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) | Intent to Treat | Posted | Count of Participants | Participants | Week 16 |
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| Secondary | Period 2: Rectal Bleeding Sub-score of 0 | Percentage of patients achieving the endpoint rectal bleeding sub-score of 0 | Intent to treat | Posted | Count of Participants | Participants | Week 16 |
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| Secondary | Period 2: Stool Frequency 0 | Percentage of patients achieving the endpoint stool frequency sub-score of 0 | Intent to Treat | Posted | Count of Participants | Participants | Week 16 |
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| 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. | Indent to Treat | Posted | Count of Participants | Participants | Week 16 |
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| Secondary | Period 2: UC-Related Complications | Percentage of Patients Experiencing Complications related to UC | Intent to Treat | Posted | Count of Participants | Participants | Week 16 |
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| 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. | Intent to Treat | Posted | Number | percentage of participants | Week 38 |
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| Secondary | Period 3: Clinical and Endoscopic Remission | Mayo Score of <= 2 points with no individual sub-score > 1 | Intent to Treat | Posted | Number | percentage of participants | Week 38 |
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| 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. | Intent to Treat | Posted | Number | percentage of participants | Week 38 |
|
|
|
| Secondary | Period 3: Endoscopic Remission | Percentage of each dose group achieving an endoscopy sub score of 0 | Intent to Treat | Posted | Number | percentage of participants | Week 38 |
|
|
|
| Secondary | Period 3: Endoscopic Response | Endoscopic response was define as a reduction in the Mayo endoscopic sub score of at least one. | Intent to Treat | Posted | Number | percentage of participants | Week 38 |
|
|
|
| Secondary | Period 3: Rectal Bleeding Sub Score of 0 | Percentage of each dose group achieving the endpoint rectal bleeding subscore 0 | Intent to Treat | Posted | Number | percentage of participants | Week 38 |
|
|
|
| Secondary | Period 3: Stool Frequency Sub-score 0 | Patients achieving a Stool Frequency sub-score of 0 | Intent to Treat | Posted | Count of Participants | Participants | Week 38 |
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|
|
| 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. | Intent to Treat | Posted | Count of Participants | Participants | Week 38 |
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|
|
| Secondary | Period 3: UC-Related Complications | Percentage of Patients with Complications related to UC | Intent to Treat | Posted | Count of Participants | Participants | Week 38 |
|
|
|
| 24 |
| 409 |
| 58 |
| 409 |
| EG001 | Asacol/TP05 | Double-blind Induction Phase: Asacol, and Open-Label Maintenance Phase: TP05 | 18 | 408 | 75 | 408 |
| EG002 | TP05 Extended Induction | Extended Induction only, Open-Label | 3 | 243 | 0 | 243 |
| EG003 | TP05 | Double-blind Induction Phase only | 9 | 409 | 26 | 409 |
| EG004 | Asacol | Double-blind Induction Phase only | 7 | 408 | 22 | 408 |
| Proctitis | Gastrointestinal disorders | MedDra (18.0) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDra (18.0) | Systematic Assessment | Iron deficiency |
|
| Ligament rupture | Injury, poisoning and procedural complications | MedDra (18.0) | Systematic Assessment |
|
| Clostridium dificile | Infections and infestations | MedDra (18.0) | Systematic Assessment |
|
| Hypertensive heart disease | Cardiac disorders | MedDra (18.0) | Systematic Assessment |
|
| Transient ischaemic attack | Nervous system disorders | MedDra (18.0) | Systematic Assessment |
|
| Artrial fibrilation | Cardiac disorders | MedDra (18.0) | Systematic Assessment |
|
| Chronic tonsilitis | Infections and infestations | MedDra (18.0) | Systematic Assessment |
|
| Tibia fracture | Injury, poisoning and procedural complications | MedDra (18.0) | Systematic Assessment |
|
| Cryoglobulinemic vasculitis | Vascular disorders | MedDra (18.0) | Systematic Assessment |
|
| Flue | Infections and infestations | MedDra (18.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDra (18.0) | Systematic Assessment |
|
| Chronic pancreatitis | Gastrointestinal disorders | MedDra (18.0) | Systematic Assessment |
|
| Unstable angina | Cardiac disorders | MedDra (18.0) | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDra (18.0) | Systematic Assessment |
|
| Cerebral haematoma | Nervous system disorders | MedDra (18.0) | Systematic Assessment |
|
| Herniated disc | Musculoskeletal and connective tissue disorders | MedDra (18.0) | Systematic Assessment |
|
| Perichondritis | Infections and infestations | MedDra (18.0) | Systematic Assessment |
|
| Acute heamorrhagic cystitis | Renal and urinary disorders | MedDra (18.0) | Systematic Assessment |
|
| Nasal septum deformation | Respiratory, thoracic and mediastinal disorders | MedDra (18.0) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDra (18.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDra (18.0) | Systematic Assessment |
|
| Diabetes melitus | Metabolism and nutrition disorders | MedDra (18.0) | Systematic Assessment |
|
| Fading fetus | Pregnancy, puerperium and perinatal conditions | MedDra (18.0) | Systematic Assessment |
|
|
Not provided
Not provided
| D002264 |
| Carboxylic Acids |
| D009930 | Organic Chemicals |
| D000636 | Aminosalicylic Acids |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D006880 | Hydroxy Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010636 | Phenols |