Clinical trial NCT00676832: Study of COLAL-PRED to Treat Moderate to Severe Ulcerative Colitis
Official title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of COLAL-PRED in the Treatment of Patients With Moderate to Severe Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colitis, Ulcerative
Keywords: colitis
ulcerative
moderate
severe
Lead sponsor: Prometheus Laboratories
Sponsor class: INDUSTRY
First posted: 2008-05-13
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether COLAL-PRED is a safe and effective treatment for patients with moderate to severe ulcerative colitis.

Detailed description: This is a multi-center, randomized, double-blind, placebo-controlled, parallel-design, dose-ranging study. Eligible patients with a DAI score of 6 to 10 (inclusive), plus endoscopic evidence of moderate to severe ulcerative colitis as assessed by flexible sigmoidoscopy, unless colonoscopy is clinically indicated, and rectal bleeding will be randomized to placebo or one of four doses of COLAL-PRED (equivalent to 40, 60, 80, or 120 mg of prednisolone). The effectiveness and safety of COLAL-PRED will be evaluated at baseline, and after 2 weeks and 4 weeks of treatment. Additional follow-up measurements will take place 7 days post cessation of treatment.

The systemic absorption of COLAL-PRED will be determined by measuring blood levels of prednisolone, prednisolone sodium metasulfobenzoate (PMSBS) and metasulfobenzoate at Week 4.

Hypothalamic-pituitary-adrenocortical (HPA) axis response will be monitored by measuring morning serum cortisol levels at Baseline, Week 2, Week 4, and at follow-up visit and cortisol levels following adrenocorticotrophic hormone (ACTH) stimulation testing at Baseline and Week 4.

Eligibility criteria: Inclusion Criteria:

* Females must be of non-childbearing potential evidenced by being surgically sterile, postmenopausal for at least 12 months or be using acceptable contraception methods such as contraceptive pill, or two forms of barrier contraception.
* Disease Activity Index (DAI) Score of 6-10 (inclusive) at the Baseline Visit.
* Previous colonoscopic and biopsy diagnosis of ulcerative colitis with negative evaluation of the ileum within 3 years of the screening visit.
* Endoscopic evidence of moderate or severe mucosal disease as assessed by flexible sigmoidoscopy, with a minimum confirmed diagnosis of moderate ulcerative colitis.
* The following concomitant prescription medications for ulcerative colitis are permitted if the following conditions are met:

  1. Oral 5-aminosalicylic acid (5-ASA )therapy if the following 2 criteria are met:

     1. Must be on a stable dose 2 weeks prior to baseline
     2. Must maintain the stable dose until treatment end.
  2. Azathioprine or 6-mercaptopurine or methotrexate if the 4 following criteria are met:

     1. On therapy continually for at least 3 months prior to baseline.
     2. And on a stable dose for at least 2 weeks prior to baseline.
     3. And must maintain the stable dose until the end of study drug treatment.

Exclusion Criteria:

* History of colonic or rectal surgery, excluding hemorrhoidal surgery or an appendectomy.
* Pregnant or breast-feeding females.
* Diagnosis of diabetes, heart failure, unstable angina, hepatic cirrhosis, kidney failure, adrenocortical insufficiency, or any other unstable medical condition.
* Known hypersensitivity to corticosteroids
* Use of oral 5-aminosalicylic acid (5-ASA) or oral corticosteroids during the immediate screening period.
* Use of immunosuppressive drugs or antibiotics at any time within four weeks prior to screening.
* Diagnosis of Crohn's disease; indeterminate colitis; microscopic colitis; ischemic, infectious (e.g., salmonella, shigella, etc.), or amebic colitis; or gonococcal proctitis; Clostridium difficile colitis.
* History of tuberculosis or HIV
* Clinically significant abnormal laboratory test results, unless regarded by the Investigator as related to ulcerative colitis
* History of alcohol or drug abuse
* Known malignancy or history of malignancy that would reduce life expectancy
* Recent immunization with live viral vaccines
* History of or active peptic ulcer disease or gastritis
* Generalized infections such as systemic fungal or hepatitis B or C
* History of steroid induced severe hypertension, steroid-induced psychosis, or any other severe steroid-related adverse reaction

Primary outcomes:
measure: The proportion of patients with Complete Response at Week 4 defined as a decrease from baseline in the DAI score by ≥ 30% or ≥ 3 points, and with a decrease in the rectal bleeding subscore of ≥ 1 or an absolute rectal bleeding sub-score of 0 or 1.
timeFrame: Week 4 of the study or at time of withdrawal
Secondary outcomes:
measure: The proportion of patients in Clinical Remission defined as a DAI score of ≤ 2 points, with no-individual DAI sub-score > 1 at Week 4. Patients in remission by this definition will have a rectal bleeding DAI sub-score of either 0 or 1.
timeFrame: Week 4
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Prometheus Investigational Site #059
state: Alabama
city: Huntsville
country: United States
facility: Prometheus Investigational Site #042
state: Alabama
city: Huntsville
country: United States
facility: Prometheus Investigational Site #081
state: Alabama
city: Montgomery
country: United States
facility: Prometheus Investigational Site #033
state: Alabama
city: Scottsdale
country: United States
facility: Prometheus Investigational Site #067
state: Arizona
city: Tucson
country: United States
facility: Prometheus Investigational Site #090
state: Arizona
city: Jonesboro
country: United States
facility: Prometheus Investigational Site #068
state: Arkansas
city: Little Rock
country: United States
facility: Prometheus Investigational Site #065
state: Arkansas
city: Lowell
country: United States
facility: Prometheus Investigational Site #093
state: Arkansas
city: Fresno
country: United States
facility: Prometheus Investigational Site 062
state: California
city: Madera
country: United States
facility: Prometheus Investigational Site #057
state: California
city: Palm Springs
country: United States
facility: Prometheus Investigational Site #060
state: California
city: Roseville
country: United States
facility: Prometheus Investigational Site #095
state: California
city: San Carlos
country: United States
facility: Prometheus Investigational Site #003
state: California
city: San Diego
country: United States
facility: Prometheus Investigational Site #022
state: California
city: Santa Monica
country: United States
facility: Prometheus Investigational Site #052
state: California
city: West Covina
country: United States
facility: Prometheus Investigational Site #086
state: California
city: Lafayette
country: United States
facility: Prometheus Investigational Site #097
state: Colorado
city: Littleton
country: United States
facility: Prometheus Investigational Site #006
state: Colorado
city: Thornton
country: United States
facility: Prometheus Investigational SIte #036
state: Colorado
city: Hamden
country: United States
facility: Prometheus Investigational Site #031
state: Connecticut
city: Hartford
country: United States
facility: Prometheus Investigational Site #083
state: Connecticut
city: Cape Coral
country: United States
facility: Prometheus Investigational Site #023
state: Florida
city: Cape Coral
country: United States
facility: Prometheus Investigational Site #075
state: Florida
city: Hollywood
country: United States
facility: Prometheus Investigational Site #076
state: Florida
city: Jacksonville
country: United States
facility: Prometheus Investigational Site #007
state: Florida
city: Miami
country: United States
facility: Prometheus Investigational Site #008
state: Florida
city: Sarasota
country: United States
facility: Prometheus Investigational Site #027
state: Florida
city: Winter Park
country: United States
facility: Prometheus Investigational Site #066
state: Florida
city: Atlanta
country: United States
facility: Prometheus Investigational Site #005
state: Georgia
city: Atlanta
country: United States
facility: Prometheus Investigational Site #044
state: Georgia
city: Arlington Heights
country: United States
facility: Prometheus Investigational Site #010
state: Illinois
city: Chicago
country: United States
facility: Prometheus Investigational Site 041
state: Illinois
city: Chicago
country: United States
facility: Prometheus Investigational Site # 001
state: Illinois
city: Peoria
country: United States
facility: Prometheus Investigational Site #089
state: Illinois
city: Anderson
country: United States
facility: Prometheus Investigational Site #059
state: Indiana
city: Davenport
country: United States
facility: Prometheus Investigational Site #015
state: Iowa
city: Topeka
country: United States
facility: Prometheus Investigational Site #051
state: Kansas
city: Baton Rouge
country: United States
facility: Prometheus Investigational Site #039
state: Louisiana
city: Lafayette
country: United States
facility: Prometheus Investigational Site #061
state: Louisiana
city: New Orleans
country: United States
facility: Prometheus Investigational Site 092
state: Louisiana
city: Shreveport
country: United States
facility: Prometheus Investigational Site 100
state: Louisiana
city: Chevy Chase
country: United States
facility: Prometheus Investigational Site #016
state: Maryland
city: Hagerstown
country: United States
facility: Prometheus Investigational Site #046
state: Maryland
city: Laurel
country: United States
facility: Prometheus Investigational Site #035
state: Maryland
city: Lutherville
country: United States
facility: Prometheus Investigational Site #025
state: Maryland
city: Boston
country: United States
facility: Prometheus Investigational Site #037
state: Massachusetts
city: Braintree
country: United States
facility: Prometheus Investigational Site #018
state: Massachusetts
city: Southbridge
country: United States
facility: Prometheus Investigational Site #091
state: Massachusetts
city: Chesterfield
country: United States
facility: Prometheus Investigational Site # 050
state: Michigan
city: Novi
country: United States
facility: Prometheus Investigational Site #011
state: Michigan
city: Wyoming
country: United States
facility: Prometheus Investigational Site #072
state: Michigan
city: Plymouth
country: United States
facility: Prometheus Investigational Site #098
state: Minnesota
city: Jackson
country: United States
facility: Prometheus Investigational Site #021
state: Mississippi
city: Mexico
country: United States
facility: Prometheus Investigational Site #019
state: Missouri
city: Lebanon
country: United States
facility: Prometheus Investigational Site #017
state: New Hampshire
city: Cedar Knolls
country: United States
facility: Prometheus Investigational Site #014
state: New Jersey
city: Egg Harbor Township
country: United States
facility: Prometheus Investigational Site #009
state: New Jersey
city: Ocean
country: United States
facility: Prometheus Investigational Site #063
state: New Jersey
city: Brooklyn
country: United States
facility: Prometheus Investigational Site #080
state: New York
city: Great Neck
country: United States
facility: Prometheus Investigational Site #002
state: New York
city: Rochester
country: United States
facility: Prometheus Investigational Site #079
state: New York
city: Rockville Center
country: United States
facility: Prometheus Investigational Site 043
state: New York
city: Stony Brook
country: United States
facility: Prometheus Investigational Site 087
state: New York
city: Charlotte
country: United States
facility: Prometheus Investigational Site #013
state: North Carolina
city: Greenville
country: United States
facility: Prometheus Investigational Site #047
state: North Carolina
city: Wilmington
country: United States
facility: Prometheus Investigational Site #058
state: North Carolina
city: Columbus
country: United States
facility: Prometheus Investigational Site #069
state: Ohio
city: Dayton
country: United States
facility: Prometheus Investigational Site #070
state: Ohio
city: Dayton
country: United States
facility: Prometheus Investigational Site #064
state: Ohio
city: Mentor
country: United States
facility: Prometheus Investigational Site #055
state: Ohio
city: Westlake
country: United States
facility: Prometheus Investigational Site #094
state: Ohio
city: Tulsa
country: United States
facility: Prometheus Investigational Site #028
state: Oklahoma
city: Tulsa
country: United States
facility: Prometheus Investigational Site #049
state: Oklahoma
city: Philadelphia
country: United States
facility: Prometheus Investigational Site #030
state: Pennsylvania
city: Philadelphia
country: United States
facility: Prometheus Investigational Site #038
state: Pennsylvania
city: Sayre
country: United States
facility: Prometheus Investigational Site #034
state: Pennsylvania
city: Charleston
country: United States
facility: Prometheus Investigational Site #045
state: South Carolina
city: Franklin
country: United States
facility: Prometheus Investigational Site #084
state: Tennessee
city: Germantown
country: United States
facility: Prometheus Investigational Site #020
state: Tennessee
city: Nashville
country: United States
facility: Prometheus Investigational Site #053
state: Tennessee
city: Union City
country: United States
facility: Prometheus Investigational Site #074
state: Tennessee
city: Denton
country: United States
facility: Prometheus Investigational Site 101
state: Texas
city: Plano
country: United States
facility: Prometheus Investigational Site #071
state: Texas
city: San Antonio
country: United States
facility: Prometheus Investigational Site #026
state: Texas
city: San Antonio
country: United States
facility: Prometheus Investigational Site #073
state: Texas
city: Sugar Land
country: United States
facility: Prometheus Investigational Site #082
state: Texas
city: Ogden
country: United States
facility: Prometheus Investigational Site #012
state: Utah
city: Seattle
country: United States
facility: Prometheus Investigational Site #040
state: Washington
Study officials:
affiliation: The University of Chicago Hospitals
name: David T. Rubin, M.D.
role: PRINCIPAL_INVESTIGATOR
References: