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

Phase 3

Completed

Conditions: Acute Ulcerative Colitis

Interventions: Drug: TP05
Drug: Asacol 400 mg

Registration Number: NCT01903252

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 817

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TP05 (Mesalazine) 1600mg	TP05	week 1 - week 12 (blinded), week 13 - week 38 (OpenLabel)
Asacol 400 mg (Tillotts Pharma)	Asacol 400 mg	week 1 - week 12 (blinded), switch to TP05 for weeks 13-38 (open label)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Period 1: Endoscopic Remission	Week 8	Endoscopic remission was defined as a Mayo endoscopy subscore of 0
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 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: 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 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 1: Clinical Remission	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: 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: 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: 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 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 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 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 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 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 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 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 3: Clinical and Endoscopic Remission	Week 38	Mayo Score of \<= 2 points with no individual sub-score \> 1
Period 3: Endoscopic Remission	Week 38	Percentage of each dose group achieving an endoscopy sub score of 0
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: 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