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TP05 for the Treatment of Mild to Moderate Active Ulcerative Colitis (UC) (Precision-UC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01903252
Recruitment Status : Completed
First Posted : July 19, 2013
Results First Posted : August 8, 2018
Last Update Posted : August 8, 2018
Sponsor:
Information provided by (Responsible Party):
Tillotts Pharma AG

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.


Condition or disease Intervention/treatment Phase
Acute Ulcerative Colitis Drug: TP05 Drug: Asacol 400 mg Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 817 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind
Primary Purpose: Treatment
Official Title: A Randomised, Active-Controlled, Double-Blind and Open Label Extensions Study to Evaluate the Efficacy, Long-Term Safety and Tolerability of TP05 3.2g/Day for the Treatment of Active Ulcerative Colitis
Actual Study Start Date : July 2013
Actual Primary Completion Date : May 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TP05 (Mesalazine) 1600mg
week 1 - week 12 (blinded), week 13 - week 38 (OpenLabel)
Drug: TP05
3.2g/day once daily for 12 weeks (blinded), 1.6g/d - 4.8g/d up to week 38 (open label)
Other Name: Mesalazine 1600 mg

Active Comparator: Asacol 400 mg (Tillotts Pharma)
week 1 - week 12 (blinded), switch to TP05 for weeks 13-38 (open label)
Drug: Asacol 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)
Other Name: Mesalazine (Tillotts Pharma AG)




Primary Outcome Measures :
  1. Period 1: Clinical and Endoscopic Remission [ Time Frame: Week 8 ]
    Mayo Score of <= 2 points with no individual sub-score > 1

  2. Period 2: Clinical Response, Open-Label Extended Induction [ Time Frame: 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.

  3. Period 3: Clinical Remission [ Time Frame: 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 Outcome Measures :
  1. Period 1: Endoscopic Remission [ Time Frame: Week 8 ]
    Endoscopic remission was defined as a Mayo endoscopy subscore of 0

  2. Period 1: Endoscopic Response [ Time Frame: Week 8 ]
    Endoscopic response was define as a reduction in the Mayo endoscopic sub score of at least one.

  3. Period 1: Clinical Remission [ Time Frame: 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)

  4. Period 1: Rectal Bleeding Sub-score of 0 [ Time Frame: Week 8 ]
    Rectal bleeding sub-score of 0 was defined as a sub score on the rectal bleeding component of the Mayo score

  5. Period 1: Clinical and Endoscopic Response [ Time Frame: 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.

  6. Period 1: Clinical Remission [ Time Frame: 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)

  7. Period 1: Clinical Response [ Time Frame: 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.

  8. Period 1: Rectal Bleeding Score of 0 [ Time Frame: Week 12 ]
    Rectal bleeding sub-score of 0 was defined as a sub score on the rectal bleeding component of the Mayo score

  9. Period 1: Clinical Remission at Both Week 8 and 12 [ Time Frame: 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)

  10. Period 1: Clinical Response at Both Week 8 and Week 12 [ Time Frame: 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.

  11. Period 1: Change in Mayo Score From Baseline [ Time Frame: 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.


  12. Period 1: Change in Partial Mayo Score From Baseline [ Time Frame: 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.

  13. Period 1: Change in Stool Frequency Score [ Time Frame: 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.

  14. Period 1: Change in Rectal Bleeding Score From Baseline [ Time Frame: 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.

  15. Period 1: Change in Physician Global Assessment Score From Baseline [ Time Frame: 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.


  16. Period 1: Change in Endoscopic Score From Baseline [ Time Frame: 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.

  17. Period 2: Clinical Remission [ Time Frame: 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)

  18. Period 2: Rectal Bleeding Sub-score of 0 [ Time Frame: Week 16 ]
    Percentage of patients achieving the endpoint rectal bleeding sub-score of 0

  19. Period 2: Stool Frequency 0 [ Time Frame: Week 16 ]
    Percentage of patients achieving the endpoint stool frequency sub-score of 0

  20. Period 2: Urgency [ Time Frame: 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.

  21. Period 2: UC-Related Complications [ Time Frame: Week 16 ]
    Percentage of Patients Experiencing Complications related to UC

  22. Period 3: Clinical Response [ Time Frame: 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.

  23. Period 3: Clinical and Endoscopic Remission [ Time Frame: Week 38 ]
    Mayo Score of <= 2 points with no individual sub-score > 1

  24. Period 3: Clinical and Endoscopic Response [ Time Frame: 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.

  25. Period 3: Endoscopic Remission [ Time Frame: Week 38 ]
    Percentage of each dose group achieving an endoscopy sub score of 0

  26. Period 3: Endoscopic Response [ Time Frame: Week 38 ]
    Endoscopic response was define as a reduction in the Mayo endoscopic sub score of at least one.

  27. Period 3: Rectal Bleeding Sub Score of 0 [ Time Frame: Week 38 ]
    Percentage of each dose group achieving the endpoint rectal bleeding subscore 0

  28. Period 3: Stool Frequency Sub-score 0 [ Time Frame: Week 38 ]
    Patients achieving a Stool Frequency sub-score of 0

  29. Period 3: No Urgency [ Time Frame: 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.

  30. Period 3: UC-Related Complications [ Time Frame: Week 38 ]
    Percentage of Patients with Complications related to UC



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01903252


Locations
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Switzerland
Tillotts Pharma AG
Rheinfelden, Baslerstrasse 15, Switzerland, 4310
Sponsors and Collaborators
Tillotts Pharma AG
Investigators
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Principal Investigator: Geert R D'Haens, MD, PhD Robarts Clinical Trials Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Tillotts Pharma AG
ClinicalTrials.gov Identifier: NCT01903252     History of Changes
Other Study ID Numbers: TP0503
First Posted: July 19, 2013    Key Record Dates
Results First Posted: August 8, 2018
Last Update Posted: August 8, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tillotts Pharma AG:
UC

Additional relevant MeSH terms:
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Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Mesalamine
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents