A BE Study Comparing Mesalamine 400 mg to ASACOL® 400 mg in Patients With Mild To Moderately Active Ulcerative Colitis

Sponsor

EMET Pharmaceuticals, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT01045018

Collaborator

Eagle Pharmaceuticals, Inc. (Industry)

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

The objectives of this bioequivalence study in patients with ulcerative colitis (UC) were:

To establish the therapeutic equivalence of mesalamine delayed release tablet (MDRT) and Asacol Delayed Release Tablets 2.4 g per day (800 mg three times daily) and
To evaluate the safety of MDRT 2.4 g per day (800 mg three times daily) compared to placebo.

Condition or Disease	Intervention/Treatment	Phase
Mild to Moderate Ulcerative Colitis	Drug: Placebo Drug: Mesalamine Drug: Mesalamine	Phase 3

Detailed Description

This was a multi-center, randomized, parallel-groups comparison of two mesalamine products for treatment of ulcerative colitis. Patients were randomly assigned in an optimized 2:2:1 ratio to MDRT 2.4 g/day, Asacol 2.4 g/day, or placebo. The study was partially blinded due to the difficulties associated with creating placebo that matched both MDRT and Asacol; the placebo matched the MDRT formulation. Placebo groups served as control in the parallel group comparison between MDRT and Asacol. Patients were treated for 6 weeks after randomization and followed through Day 56, which was considered of sufficient length to accommodate any safety issues and to assess efficacy based upon prior clinical trials of mesalamine in patients with mild to moderate active UC as described in the introduction

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Official Title:

BE Study With Clinical Endpoints Comparing Mesalamine Delayed Release Tablets 400 mg to the Reference Listed Drug ASACOL® Delayed Release Tablets 400 mg in Patients With Mild to Moderately Active Ulcerative Colitis

Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

Jun 1, 2009

Actual Study Completion Date :

Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: mesalamine 400 mg tablet	Drug: Mesalamine
Active Comparator: Asacol 400 mg Delayed Release Tablet	Drug: Mesalamine
Placebo Comparator: Placebo delayed release tablet	Drug: Placebo placebo 400 mg

Arm

Intervention/Treatment

Active Comparator: mesalamine 400 mg tablet

Drug: Mesalamine

Active Comparator: Asacol 400 mg Delayed Release Tablet

Drug: Mesalamine

Placebo Comparator: Placebo delayed release tablet

Drug: Placebo

placebo 400 mg

Outcome Measures

Primary Outcome Measures

Treatment Success: Responders are patients in remission or who do not require use of rescue medication for symptomatic relief of UC at week 6 Treatment benefit: Improvement at endpoint compared to baseline Treatment Failure: Increase or no improvement [4 months]

Secondary Outcome Measures

Tolerability and safety will be determined by evaluation of AEs, SAEs, hematology, serum chemistry and urinalysis [4 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults with newly diagnosed ulcerative colitis or with relapse following prior treatment and who met all the following criteria were eligible for participation in the study:

IRB approved consent form signed and dated prior to any study-related activities
Male or, if female, had undergone sterilization (hysterectomy or bilateral tubal ligation), was post-menopausal (defined as 1 year without menses) or has a negative pregnancy test at screening and, if heterosexually active, had used and agreed to continue to use: double-barrier method of contraception (condom and spermicide), oral or patch contraceptives, intrauterine device, or was in a monogamous relationship with a partner who had undergone a vasectomy.
18 years of age or older
Newly diagnosed with ulcerative colitis or relapsed following prior treatment
Patient had not taken > 1.6 g/day of mesalamine or equivalent for 14 days prior to randomization
Disease extending ≥ 15 cm above the anal verge on screening sigmoidoscopy or colonoscopy with confirming biopsy
Mild to moderate ulcerative colitis, defined as a Disease Activity Index (DAI) score between 4 and 9, inclusive, at study entry, and with a PGA of 1 or 2 and mucosal appearance (determined by endoscopy exam) score of 1 or 2 (mild/moderate)
Able and willing to have kept a daily diary during the study

Exclusion Criteria:

Treatment with topical rectal, oral, or intravenous (IV) corticosteroids within 30 days of screening or immunosuppressives (e.g. azathioprine, 6-mercaptopurine) within the 90 days immediately preceding Screening
Use of rectal - administered aminosalicylates within 7 days of randomization
Patient had taken greater than 1.6 g/day of mesalamine or equivalent within 14 days of randomization
Crohn's disease, ischemic colitis, or disease of bacterial origin
Known allergy or hypersensitivity to aspirin or salicylate compounds
History of or laboratory results showing significant hepatic or renal disease or other significant medical condition which in the opinion of the investigator precluded participation in the study based on efficacy/safety assessments
History of cancer other than basal cell carcinoma within the five years immediately preceding study entry
In relapse for > 3 weeks prior to the screening visit
Proctitis below 15 cm from the anal verge
History of or current gastrointestinal bleeding other than bloody stools associated with ulcerative colitis
History of bleeding disorder
Active peptic ulcer disease, history of gastrointestinal obstruction including severe constipation, or anatomic abnormality of the GI tract
Previous colonic surgery
History of alcohol or other substance abuse within the year immediately preceding anticipated study entry
HIV positive
6 bloody stools per day
Positive stool culture for ova and/or parasites, enteric pathogens including Salmonella, Shigella, Yersinia, and Campylobacter, or positive stool assay for C. difficile toxin
Pregnant or breast feeding
Used an investigational drug in the 30 days prior to randomization
BUN or serum creatinine levels of 1.5 times the upper limit of normal (ULN) or liver enzyme levels > 2 times the ULN