Once Daily Versus Conventional Dosing of Asacol in the Maintenance of Quiescent Ulcerative Colitis
Information source: University of Chicago
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Ulcerative Colitis
Intervention: Asacol (mesalamine) (Drug)
Phase: Phase 3
Sponsored by: University of Chicago
Official(s) and/or principal investigator(s):
Sunanda Kane, MD, Principal Investigator, Affiliation: University of Chicago
The purpose of this study is to determine if taking Asacol once a day is as effective as
taking Asacol twice or three times a day in keeping ulcerative colitis inactive, and to
determine which dosing regimen is easiest to follow. Once daily dosing of Asacol is
experimental, and has not been approved by the FDA. Dosing as three times daily is FDA
This research is being done because the researchers want to learn what the best methods are
for keeping ulcerative colitis inactive, and which way of taking Asacol is most helpful to
subjects in continuing to take a medication to control their ulcerative colitis.
Official title: Once Daily Versus Conventional Dosing of Asacol in the Maintenance of Quiescent Ulcerative Colitis: A Randomized Pilot Trial
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Prevention
calculation of medication consumption rates at months 3, 6, 9 and 12
12-month study period
Hypothesis: Asacol taken once a day is equally effective (non-inferior) as conventional
(twice or three times a day) dosing at maintaining remission in quiescent ulcerative
1. To assess the efficacy of once daily Asacol in the short and long-term maintenance of
remission in quiescent ulcerative colitis.
2. To assess the medication consumption rate (adherence) in patients prescribed once daily
Asacol compared to a bid or tid regimen.
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease of the large
intestine characterized by episodes of relapse and remission. Relapses are often not
predictable, although factors such as smoking cessation, chronic non-steroidal
antiinflammatory use and psychological stress are thought to cause symptom exacerbation in
Multiple studies have demonstrated the efficacy of aminosalicylates to induce and maintain
remission in UC. Because of its chronic nature, therapy often must continue on an
indefinite basis. Many patients openly admit they do not take their medications as
prescribed; medication-taking probably makes patients more uncomfortably aware of their
chronic illness status, they have a fear of long-term side effects from medications, and
they question the need for medication in the setting of quiescent disease.
Previous work done at the University of Chicago demonstrated that using objective pharmacy
data, rather than patient-derived information, the prevalence of medication non-adherence
was 60% in patients with quiescent UC. The average amount of medication consumed was 70% of
that prescribed. In a prospective study, those patients non-adherent with medications had a
higher risk of relapse than those who consumed greater than 75% of their prescribed regimen.
It is difficult to get patients to take medication when they feel well, because the
rationale for continued use remains unclear to them. The long-term goals of improving
adherence are to reduce frequency of relapse, lower the incidence of long-term complications
(i. e. colon cancer), and lower overall health costs. Making a regimen easy for patients is
a key factor in increasing adherence.
Hussain recently showed that in normal subjects, median peak concentrations, trough
concentrations and areas under the curve were similar for Asacol consumed either as a once
or three times daily dosing regimen. Twenty-four hour urinary and fecal excretions, total
recovery, and rectal tissue concentrations also were similar in both groups. The authors
concluded that the steady-state pharmacokinetics of delayed-release Asacol was similar
whether the drug was administered in three divided doses throughout the day or as a single
There are data to suggest that the motility and function of the colon in patients with
quiescent ulcerative colitis is similar to that of normal subjects. If this is indeed the
case, then the pharmacokinetics of Asacol should mimic those of healthy controls. In a small
pilot study, we were able to show that in a 6-month time, patients were no more likely to
experience a flare of their disease and actually consumed more medication in a once daily
regimen than in a standard regimen. The aim of this study is to test this hypothesis in a
larger number of patients, and assess the efficacy of once daily Asacol in patients with
quiescent ulcerative colitis compared to a twice or three times daily regimen. In addition,
we wish to compare the rates of medication consumption between groups over a prolonged
period of time.
Patients eligible will be asked to sign informed consent prior to participation. As part of
the consent process, the phone number of the patient pharmacy will be collected. Patients
will then be randomized to one of two groups: once daily or usual (twice daily or three
times daily) therapy. Assignment will be via the use of opaque sealed envelopes, containing
assignment based on a randomization table. Once enrolled, each patient will be assigned a
study number, which will be used on the questionnaires to maintain confidentiality. The
patients will be instructed to conceal their regimen from any research investigator.
Patients will be followed prospectively and assessed at 3 month intervals from enrollment.
The three and nine-month follow up will be via phone contact by one of the study nurses.
Disease assessment and quality of life will be obtained by the nurse in a standard fashion.
At time intervals 6 and 12 months, patients will be assessed during a scheduled clinic
visit, using the same assessment tools along with a physical exam. These visits will not be
additional or extra visits, but part of standard of care for ulcerative colitis. There will
be no additional blood draws or endoscopy as part of the protocol, lab work and endoscopy
for patient care as determined by each treating physician will be documented.
Medication consumption rates at months 3, 6, 9 and 12 will be calculated using pharmacy data
as obtained by telephone by the PI and the validated formula as described by Steiner and
colleagues. The end point of the study is disease relapse or the 12-month study period. An
investigator blinded to the treatment regimen will assess the outcomes and medication
consumption rates for each group. Patients experiencing a flare during the study period will
be treated as deemed necessary by their treating physician.
Minimum age: 18 Years.
Maximum age: N/A.
- Adult patients over the age of 18 followed at the University of Chicago Outpatient
Gastroenterology Clinic will be eligible. Patients must have documentation of
ulcerative colitis by standard criteria, and be in remission for at least 4 months
prior to study entry. Remission for this study will be defined clinically, as the
absence of all of the following: blood in the stools, urgency, or cramping. Patients
must be taking a regimen of Asacol (Asacol, Procter and Gamble, Cincinnati Ohio) for
maintenance of quiescent disease
- Exclusion criteria include documented disease activity in the past four months,
hospitalization or steroid use for disease activity in the previous 4 months, or the
use of other immunomodulators to induce remission. Patients with a history of other
diarrheal illnesses such as diarrhea-predominant Irritable Bowel Syndrome, C
difficile colitis, use of known diarrheal drugs will also be excluded.
Locations and Contacts
The University of Chicago, Chicago, Illinois 60637, United States
Silverstein MD, Lashner BA, Hanauer SB. Cigarette smoking and ulcerative colitis: a case-control study. Mayo Clin Proc. 1994 May;69(5):425-9.
Fraga XF, Vergara M, Medina C, Casellas F, Bermejo B, Malagelada JR. Effects of smoking on the presentation and clinical course of inflammatory bowel disease. Eur J Gastroenterol Hepatol. 1997 Jul;9(7):683-7.
Starting date: September 2006
Last updated: January 9, 2013