Clinical trial NCT01059344: Efficacy and Safety of Asacol™ 4.8 g/Day (800 mg Tablets) for the Treatment of Active Ulcerative Colitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ulcerative Colitis
Keywords: Mesalamine
Asacol
Ulcerative colitis
induction therapy
acute disease
mild to moderate
Active Ulcerative Colitis (mild to moderate)
Lead sponsor: Tillotts Pharma AG
Sponsor class: INDUSTRY
First posted: 2010-01-29
Enrollment: 281
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To Achieve Clinical Remission in Subjects With Active Ulcerative Colitis (UC).
timeFrame: 6 weeks
Secondary outcomes:
measure: Clinical Remission
timeFrame: 10 weeks
measure: Endoscopic Remission
timeFrame: 6 weeks
measure: Endoscopic Remission
timeFrame: 10 weeks
measure: Improvement
timeFrame: 6 weeks
measure: Improvement
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Gomel
country: Belarus
facility: Gomel Regional Clinical Hospital, 9
city: Minsk
country: Belarus
facility: City Clinical Hospital No.1
city: Minsk
country: Belarus
facility: Minsk Regional Clinical Hospital, 41
city: Minsk
country: Belarus
facility: City Clinical Hospital No. 2
city: Minsk
country: Belarus
facility: E.Klumov City Clinical Hospital No. 3
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Hospital
city: Hyderabad
country: India
facility: Medwin Hospital
state: Andhrapradesh
city: Hyderabad
country: India
facility: Osmania General Hospital
state: Andhrapradesh
city: Bangalore
country: India
facility: M.S.Ramiah Hospital
state: Karnataka
city: Trivandrum
country: India
facility: Shree Gokulam Medical College and Research Foundation
state: Kerala
city: Jaipur
country: India
facility: S. R. Kalla Memorial Gastro and General Hospital
state: Rajasthan
city: Chennai
country: India
facility: Life Line Hospital
state: TamilNadu
city: New Delhi
country: India
facility: Maulana Azad Medical College and Associated Lok Nayak Hospital
city: New Delhi
country: India
facility: Institute of liver and billiary sciences
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty Sihhiye
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty Sihhiye
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty Besevler
city: Diyarbakir
country: Turkey
facility: Dicle University Medical Faculty
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty
city: Gaziantep
country: Turkey
facility: Gaziantep University Medical Faculty Kampus Alani
city: Istanbul
country: Turkey
facility: Sisli Etfal Egitim ve Arastirma Hospital Sisli
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medical Faculty Inciralti
city: Izmir
country: Turkey
facility: Ataturk Egitim ve Arastirma Hospital Basin Sitesi
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovska derzhavna medychna akademiia,
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivskyi natsionalnyi medychnyi universytet,
city: Kharkiv
country: Ukraine
facility: Miska klinichna likarnia 2,
city: Kyiv
country: Ukraine
facility: Natsionalnyi medychnyi universytet im. Bogomoltsia, kafedra khirurgii 1 na bazi viddilennia proctologii Miskoi klinichnoi likarni 18, m.Kyiv
city: Kyiv
country: Ukraine
facility: Natsionalnyi medychnyi universytet im. O.O. Bogomoltsia,
city: Kyiv
country: Ukraine
facility: Natsionalna medychna akademia pisliadyplomnoi osvity im. P.L. Shupyk,
city: Lviv
country: Ukraine
facility: Lvivskyi natsionalnyi medychnyi universytet imeni Danyla Galytskogo,
city: Odessa
country: Ukraine
facility: Odeska oblasna klinichna likarnia, Oblasnyi tsentr gastroenterologii,
Study officials:
affiliation: Alimentiv Inc.
name: Brian Feagan, MD
role: STUDY_CHAIR
References:
citation: 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.