Efficacy and Safety of Asacol™ 4.8 g/Day (800 mg Tablets) for the Treatment of Active Ulcerative Colitis

A Randomized Placebo-Controlled Double-Blind Study to Evaluate the Efficacy and Safety of Asacol™ 4.8 g/Day (800 mg Tablets) for the Treatment of Active Ulcerative Colitis

The primary objective of the study is to determine the efficacy of Asacol™ 4.8 g/day (800 mg tablets) to induce clinical and endoscopic remission after 6 weeks of treatment compared to placebo in subjects with active ulcerative colitis (UC).

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Mesalamin

Detailed Description

The 800 mg Asacol™ tablets from Tillotts Pharma AG are being marketed in over 30 countries, mainly in Europe and Asia. Approved dosages for the treatment of active UC are between 2.4 and 4.8 g/day in analogy to the approved 400 mg dosage form. The present trial is planned to generate efficacy data to support the safe use of a 4.8 g/day dose of the 800 mg dosage form in a well defined population of patients with mildly to moderately active UC. In keeping with the EMEA UC guideline the study will have a placebo-controlled 6 weeks induction treatment. After 6 weeks, treatment success will be evaluated using the modified UC disease activity index as primary efficacy measurement.

• Study Type: Interventional
• Enrollment (Actual): 281
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Gomel, Belarus, 23602
    • Gomel Regional Clinical Hospital, 9
  • Minsk, Belarus, 220013
    • City Clinical Hospital No.1
  • Minsk, Belarus, 2230
    • Minsk Regional Clinical Hospital, 41
  • Minsk, Belarus
    • City Clinical Hospital No. 2
  • Minsk, Belarus
    • E.Klumov City Clinical Hospital No. 3
  • Vitebsk, Belarus, 210037
    • Vitebsk Regional Clinical Hospital
• India
  • New Delhi, India, 110 002
    • Maulana Azad Medical College and Associated Lok Nayak Hospital
  • New Delhi, India, 110 070
    • Institute of liver and billiary sciences
  • Andhrapradesh
    • Hyderabad, Andhrapradesh, India, 500 001
      • Medwin Hospital
    • Hyderabad, Andhrapradesh, India, 500 012
      • Osmania General Hospital
  • Karnataka
    • Bangalore, Karnataka, India, 560 054
      • M.S.Ramiah Hospital
  • Kerala
    • Trivandrum, Kerala, India, 695 607
      • Shree Gokulam Medical College and Research Foundation
  • Rajasthan
    • Jaipur, Rajasthan, India, 302 001
      • S. R. Kalla Memorial Gastro and General Hospital
  • TamilNadu
    • Chennai, TamilNadu, India, 600 096
      • Life Line Hospital
• Turkey
  • Ankara, Turkey, 06100
    • Ankara University Medical Faculty Sihhiye
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty Sihhiye
  • Ankara, Turkey, 06500
    • Gazi University Medical Faculty Besevler
  • Diyarbakir, Turkey, 21280
    • Dicle University Medical Faculty
  • Edirne, Turkey, 22030
    • Trakya University Medical Faculty
  • Gaziantep, Turkey, 27310
    • Gaziantep University Medical Faculty Kampus Alani
  • Istanbul, Turkey, 34360
    • Sisli Etfal Egitim ve Arastirma Hospital Sisli
  • Izmir, Turkey, 35340
    • Dokuz Eylul University Medical Faculty Inciralti
  • Izmir, Turkey, 35360
    • Ataturk Egitim ve Arastirma Hospital Basin Sitesi
• Ukraine
  • Dnipropetrovsk, Ukraine, 4904
    • Dnipropetrovska derzhavna medychna akademiia,
  • Ivano-Frankivsk, Ukraine
    • Ivano-Frankivskyi natsionalnyi medychnyi universytet,
  • Kharkiv, Ukraine, 61001
    • Miska klinichna likarnia 2,
  • Kyiv, Ukraine, 01030
    • Natsionalnyi medychnyi universytet im. Bogomoltsia, kafedra khirurgii 1 na bazi viddilennia proctologii Miskoi klinichnoi likarni 18, m.Kyiv
  • Kyiv, Ukraine, 04053
    • Natsionalnyi medychnyi universytet im. O.O. Bogomoltsia,
  • Kyiv, Ukraine, 04201
    • Natsionalna medychna akademia pisliadyplomnoi osvity im. P.L. Shupyk,
  • Lviv, Ukraine
    • Lvivskyi natsionalnyi medychnyi universytet imeni Danyla Galytskogo,
  • Odessa, Ukraine, 65039
    • Odeska oblasna klinichna likarnia, Oblasnyi tsentr gastroenterologii,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

(1) Male or non-pregnant, non-lactating females, 18 years of age or older. (2) Documented diagnosis of UC with disease extending at least 15 cm from the anal verge.

(3) Active UC defined by:

(a) modified UC-DAI score of 4-10 with (b) sigmoidoscopy component score ≥ 2 and (c) rectal bleeding component score ≥ 1 (4) Ability of subject to participate fully in all aspects of this clinical trial.

(5) Written informed consent must be obtained and documented.

Exclusion Criteria:

1. Severe UC defined by the following criteria:

   ³6 bloody stools daily with one or more of the following:

   1. oral temperature > 37.8°C or > 100.0°F
   2. pulse > 90/min
   3. hemoglobin < 10 g/dL
2. Previously failed treatment with a mesalazine dose of > 2.0 g/day.
3. Current relapse lasting > 6 weeks in the opinion of the investigator.
4. Treatment with 5-ASA at a dose of >2.0g/day within 1 week prior to randomisation
5. Treatment with systemic or rectal steroids within 4 weeks prior to randomization.
6. Treatment with immunosuppressants within 6 weeks prior to randomization.
7. Treatment with infliximab or other biologics within 3 months prior to randomization.
8. Treatment with systemic antibiotics for UC within 7 days prior to randomization.
9. Treatment with probiotics within 7 days prior to randomization.
10. Treatment with anti-diarrheals within 7 days prior to randomization.
11. Treatment with nicotine patch within 7 days prior to randomization.
12. Received any investigational drug within 30 days prior to randomization.
13. History of colectomy or partial colectomy.
14. History of definite dysplasia in colonic biopsies.
15. Crohn's disease.
16. Known bleeding disorders.
17. Immediate or significant risk of toxic megacolon.
18. Hypersensitivity to salicylates, aspirin, sulfasalazine or 5-ASA.
19. Serum creatinine > 1.5 times the upper limit of the normal range.
20. AST, ALT, total bilirubin or alkaline phosphatase > 2 times the upper limit of the normal range.
21. Serious underlying disease other than UC which in the opinion of the investigator may interfere with the subject's ability to participate fully in the study.
22. 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.
23. Stools positive for clostridium difficile.
24. Pregnant or lactating women.
25. Prior enrolment in the current study and had received study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesalamin; 4.8g Mesalamin (800mg tablet)	Drug: Mesalamin; 4.8g/day, 800 mg tablets; Other Names: Asacol
Placebo Comparator: Placebo; 4.8g Placebo to Mesalamin (800 mg tablet)	Drug: Mesalamin; 4.8g/day, 800 mg tablets; Other Names: Asacol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Achieve Clinical Remission in Subjects With Active Ulcerative Colitis (UC).	Clinical remission defined as stool frequency score of 0, rectal bleeding score of 0, no urgency	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Remission	Clinical remission defined as a score of 0 for stool frequency, 0 for rectal bleeding and no urgency	10 weeks
Endoscopic Remission	Endoscopic remission is defined as a sigmoidoscopy score of 1 or less	6 weeks
Endoscopic Remission	Endoscopic remission is defined as a sigmoidoscopy score of 1 or less	10 weeks
Improvement	Improvement is defined as a reduction of at least 3 points from baseline in the modified UC-DAI score. (minumum 3, maximum 7, higher absolute UC-DAI scores indicate more severe disease)	6 weeks
Improvement	Improvement is defined as a reduction of at least 3 points from baseline in the modified UC-DAI score. (minumum 3, maximum 7, higher absolute UC-DAI scores indicate more severe disease)	10 weeks

Collaborators and Investigators

• Sponsor: Tillotts Pharma AG
• Investigators: Study Chair: Brian Feagan, MD, Alimentiv Inc.

Publications and helpful links

General Publications

• Feagan BG, Sandborn WJ, D'Haens G, Pola S, McDonald JWD, Rutgeerts P, Munkholm P, Mittmann U, King D, Wong CJ, Zou G, Donner A, Shackelton LM, Gilgen D, Nelson S, Vandervoort MK, Fahmy M, Loftus EV Jr, Panaccione R, Travis SP, Van Assche GA, Vermeire S, Levesque BG. The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis. Gastroenterology. 2013 Jul;145(1):149-157.e2. doi: 10.1053/j.gastro.2013.03.025. Epub 2013 Mar 22.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: January 28, 2010
• First Submitted That Met QC Criteria: January 28, 2010
• First Posted (Estimate): January 29, 2010

Study Record Updates

• Last Update Posted (Actual): August 2, 2017
• Last Update Submitted That Met QC Criteria: June 27, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Ulcerative colitis; induction therapy; Mesalamine; Asacol; mild to moderate; acute disease; Active Ulcerative Colitis (mild to moderate)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: TP0203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No