Study of COLAL-PRED to Treat Moderate to Severe Ulcerative Colitis

Colitis, Ulcerative Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00676832
• Other study ID #: 08CP01
• Status: Completed
• Phase: Phase 2
• First received: May 9, 2008
• Last updated: September 27, 2010
• Start date: May 2008
• Est. completion date: October 2009

Study information

• Verified date: September 2010
• Source: Prometheus Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• Placebo
Placebo solid capsule dosage form administered orally once daily.
• COLAL-PRED
The study is a double-blinded and results have not been unblinded. Patients were randomized to one of four doses. A solid capsule dosage form was administered orally once daily at doses of 40 mg, 60 mg, 80 mg, or 120 mg.

Locations

Country	Name	City	State
United States	Prometheus Investigational Site #059	Anderson	Indiana
United States	Prometheus Investigational Site #010	Arlington Heights	Illinois
United States	Prometheus Investigational Site #005	Atlanta	Georgia
United States	Prometheus Investigational Site #044	Atlanta	Georgia
United States	Prometheus Investigational Site #039	Baton Rouge	Louisiana
United States	Prometheus Investigational Site #059	Birmingham	Alabama
United States	Prometheus Investigational Site #037	Boston	Massachusetts
United States	Prometheus Investigational Site #018	Braintree	Massachusetts
United States	Prometheus Investigational Site #080	Brooklyn	New York
United States	Prometheus Investigational Site #023	Cape Coral	Florida
United States	Prometheus Investigational Site #075	Cape Coral	Florida
United States	Prometheus Investigational Site #014	Cedar Knolls	New Jersey
United States	Prometheus Investigational Site #045	Charleston	South Carolina
United States	Prometheus Investigational Site #013	Charlotte	North Carolina
United States	Prometheus Investigational Site # 050	Chesterfield	Michigan
United States	Prometheus Investigational Site #016	Chevy Chase	Maryland
United States	Prometheus Investigational Site # 001	Chicago	Illinois
United States	Prometheus Investigational Site 041	Chicago	Illinois
United States	Prometheus Investigational Site #069	Columbus	Ohio
United States	Prometheus Investigational Site #015	Davenport	Iowa
United States	Prometheus Investigational Site #064	Dayton	Ohio
United States	Prometheus Investigational Site #070	Dayton	Ohio
United States	Prometheus Investigational Site 101	Denton	Texas
United States	Prometheus Investigational Site #009	Egg Harbor Township	New Jersey
United States	Prometheus Investigational Site #084	Franklin	Tennessee
United States	Prometheus Investigational Site 062	Fresno	California
United States	Prometheus Investigational Site #020	Germantown	Tennessee
United States	Prometheus Investigational Site #002	Great Neck	New York
United States	Prometheus Investigational Site #047	Greenville	North Carolina
United States	Prometheus Investigational Site #046	Hagerstown	Maryland
United States	Prometheus Investigational Site #031	Hamden	Connecticut
United States	Prometheus Investigational Site #083	Hartford	Connecticut
United States	Prometheus Investigational Site #076	Hollywood	Florida
United States	Prometheus Investigational Site #042	Huntsville	Alabama
United States	Prometheus Investigational Site #081	Huntsville	Alabama
United States	Prometheus Investigational Site #021	Jackson	Mississippi
United States	Prometheus Investigational Site #007	Jacksonville	Florida
United States	Prometheus Investigational Site #068	Jonesboro	Arkansas
United States	Prometheus Investigational Site #061	Lafayette	Louisiana
United States	Prometheus Investigational Site #097	Lafayette	Colorado
United States	Prometheus Investigational Site #035	Laurel	Maryland
United States	Prometheus Investigational Site #017	Lebanon	New Hampshire
United States	Prometheus Investigational Site #065	Little Rock	Arkansas
United States	Prometheus Investigational Site #006	Littleton	Colorado
United States	Prometheus Investigational Site #093	Lowell	Arkansas
United States	Prometheus Investigational Site #025	Lutherville	Maryland
United States	Prometheus Investigational Site #057	Madera	California
United States	Prometheus Investigational Site #055	Mentor	Ohio
United States	Prometheus Investigational Site #019	Mexico	Missouri
United States	Prometheus Investigational Site #008	Miami	Florida
United States	Prometheus Investigational Site #033	Montgomery	Alabama
United States	Prometheus Investigational Site #053	Nashville	Tennessee
United States	Prometheus Investigational Site 092	New Orleans	Louisiana
United States	Prometheus Investigational Site #011	Novi	Michigan
United States	Prometheus Investigational Site #063	Ocean	New Jersey
United States	Prometheus Investigational Site #012	Ogden	Utah
United States	Prometheus Investigational Site #060	Palm Springs	California
United States	Prometheus Investigational Site #089	Peoria	Illinois
United States	Prometheus Investigational Site #030	Philadelphia	Pennsylvania
United States	Prometheus Investigational Site #038	Philadelphia	Pennsylvania
United States	Prometheus Investigational Site #071	Plano	Texas
United States	Prometheus Investigational Site #098	Plymouth	Minnesota
United States	Prometheus Investigational Site #079	Rochester	New York
United States	Prometheus Investigational Site 043	Rockville Center	New York
United States	Prometheus Investigational Site #095	Roseville	California
United States	Prometheus Investigational Site #026	San Antonio	Texas
United States	Prometheus Investigational Site #073	San Antonio	Texas
United States	Prometheus Investigational Site #003	San Carlos	California
United States	Prometheus Investigational Site #022	San Diego	California
United States	Prometheus Investigational Site #052	Santa Monica	California
United States	Prometheus Investigational Site #027	Sarasota	Florida
United States	Prometheus Investigational Site #034	Sayre	Pennsylvania
United States	Prometheus Investigational Site #067	Scottsdale	Arizona
United States	Prometheus Investigational Site #040	Seattle	Washington
United States	Prometheus Investigational Site 100	Shreveport	Louisiana
United States	Prometheus Investigational Site #091	Southbridge	Massachusetts
United States	Prometheus Investigational Site 087	Stony Brook	New York
United States	Prometheus Investigational Site #082	Sugar Land	Texas
United States	Prometheus Investigational SIte #036	Thornton	Colorado
United States	Prometheus Investigational Site #051	Topeka	Kansas
United States	Prometheus Investigational Site #090	Tucson	Arizona
United States	Prometheus Investigational Site #028	Tulsa	Oklahoma
United States	Prometheus Investigational Site #049	Tulsa	Oklahoma
United States	Prometheus Investigational Site #074	Union City	Tennessee
United States	Prometheus Investigational Site #086	West Covina	California
United States	Prometheus Investigational Site #094	Westlake	Ohio
United States	Prometheus Investigational Site #058	Wilmington	North Carolina
United States	Prometheus Investigational Site #066	Winter Park	Florida
United States	Prometheus Investigational Site #072	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Prometheus Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Week 4 of the study or at time of withdrawal
Secondary	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.		Week 4