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

NCT01903252 | Completed Phase 3 Results

• 1 other identifier: TP0503
• Study Type: interventional
• Target: 817
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Ulcerative Colitis

Keywords

UC

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (30)

• Period 1: Endoscopic Remission

  Week 8

• Period 1: Endoscopic Response

  Week 8

• Period 1: Clinical Remission

  Week 8

• Period 1: Rectal Bleeding Sub-score of 0

  Week 8

• Period 1: Clinical and Endoscopic Response

  Week 8

Study Arms (2)

TP05 (Mesalazine) 1600mg

EXPERIMENTAL

week 1 - week 12 (blinded), week 13 - week 38 (OpenLabel)

Drug: TP05

Asacol 400 mg (Tillotts Pharma)

ACTIVE COMPARATOR

week 1 - week 12 (blinded), switch to TP05 for weeks 13-38 (open label)

Drug: Asacol 400 mg

Interventions

TP05 DRUG

3.2g/day once daily for 12 weeks (blinded), 1.6g/d - 4.8g/d up to week 38 (open label)

Also known as: Mesalazine 1600 mg

TP05 (Mesalazine) 1600mg

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)

Also known as: Mesalazine (Tillotts Pharma AG)

Asacol 400 mg (Tillotts Pharma)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Tillotts Pharma AG: lead

Study Sites (1)

Tillotts Pharma AG

Rheinfelden, Baslerstrasse 15, 4310, Switzerland

Location

Related Publications (3)

• 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.

  PMID: 33279779 DERIVED

• 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.

  PMID: 31546056 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.

  PMID: 28568974 DERIVED

MeSH Terms

Interventions

Mesalamine

Intervention Hierarchy (Ancestors)

meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Results Point of Contact

• Title: Dr. Robert Hofmann, MD PhD
• Organization: Tillotts Pharma AG

robert.hofmann@tillotts.com

+4161 935 27 14

Study Officials

• Geert R D'Haens, MD, PhD

  Alimentiv Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2013
• First Posted: July 19, 2013
• Study Start: July 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: November 1, 2016
• Last Updated: August 8, 2018
• Results First Posted: August 8, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)