Clinical trial NCT00326209: Long-Term Safety and Tolerability of Mesalamine Pellets in Participants With Ulcerative Colitis in Remission
Official title: A Multicenter, Open-Label, Treatment Extension Trial to Evalaute the Long-Term Safety and Tolerability of Mesalamine Pellet Formulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ulcerative Colitis
Keywords: UC
Ulcerative colitis
Inflammatory bowel disease
IBD
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2006-05-16
Enrollment: 393
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the long-term safety and tolerability of encapsulated mesalamine Granules (eMG) (formerly referred to as Mesalamine Pellets \[MP\]) in participants with ulcerative colitis currently in remission.

Detailed description: This is a Phase 3, multicenter, open-label, treatment extension study evaluating the long-term safety and tolerability of eMG given once daily (QD) in participants who successfully participated in a double-blind lead-in study (MPUC3003 \[NCT00744016 \] or MPUC3004 \[NCT00767728 \]) or new participants who are currently in remission from symptoms of ulcerative colitis.

Eligibility criteria: Inclusion Criteria:

1. An Institutional Review Board (IRB)/Ethics Committee (EC) approved informed consent is signed and dated prior to any study-related activities.
2. Participant has successfully participated in a previous MP clinical study per investigator's discretion with successful participation minimally defined as compliant with study-related procedures and study drug dosing schedule in the previous study and did not discontinue from the previous study due to study drug-related AE(s) or if new participants:

   a. Participant is a male or,

   If the participant is female, she is eligible to enter if she is of:

   Non-childbearing potential (that is; physiologically incapable of becoming pregnant, including any female who has undergone sterilization \[hysterectomy or bilateral tubal ligation\] or is post-menopausal. For purposes of this study, postmenopausal is defined as 1 year without menses); or childbearing potential, has a negative serum pregnancy test at screen and, if heterosexually active, agrees to one of the following:

   i) Double barrier method of contraception, specifically, use of a condom and spermicide, for 1 week prior to study drug administration, throughout the 6-month Treatment Phase, and the 2-week follow-up phase.

   ii) Oral contraceptives administered for at least 2 monthly cycles prior to study drug administration during all 6 months of study drug administration and administered for 1 monthly cycle following completion of the study.

   iii) An intrauterine device (IUD), inserted by a qualified clinician, with published data showing that the lowest expected failure rate is less than (\<)1% per year (not all IUDs meet this criterion).

   iv) Medroxyprogesterone acetate (DEPO-PROVERA) administered for a minimum of 1 monthly cycle prior to the study drug administration, during all 6 months of study drug administration, and administered for 1 monthly cycle following study completion. Norelgestromin/ ethinyl estradiol transdermal system (Ortho Evra patch) administered for at least 2 monthly cycles prior to study drug administration and administered for 2 monthly cycles following study completion.

   v) Partner has undergone vasectomy and participant is in a monogamous relationship.

   The investigator is responsible for determining whether the participant has adequate birth control for study participation.

   b. Participant is greater than or equal to (≥) 18 years of age. c. Participant has historically confirmed diagnosis (physician letter for newly/recently diagnosed and by medical records for previously diagnosed participants) of mild to moderate UC in remission for greater than (\>) 1 month and \<12 months.

   d. Confirmed current remission defined as both: A screening rectal bleeding score of 0 as described in the Disease Activity Index (DAI) (Sutherland Index) where 0 = None A screening sigmoidoscopy score of 0 to 1 for mucosal appearance as described in the (Sutherland Index where 0 = intact mucosa with preserved or distorted vessels and 1 = Erythema, decreased vascular pattern, granularity, no mucosal hemorrhage.
3. Participant and investigator consider there is the potential for benefit to the participant with MP treatment.
4. Participant is capable and willing to comply with all study procedures.

Exclusion Criteria:

1. Participant has any condition or circumstance that would, in the opinion of the investigator, prevent completion of the study or interfere with analysis of study results, including history of noncompliance with treatments or visits.

   If a new participant, the following additional exclusion criteria will apply:
2. Participant has a history of allergy or intolerance to aspirin, mesalamine or other salicylates.
3. Participant has an abnormal clinical lab result which in the opinion of the investigator is significant enough to prevent participant's enrollment in the study.
4. Participant or participant's parents are known to have phenylketonuria.
5. Participant has participated in an investigational drug or device study within the 30 days prior to study screening.
6. Participant shows evidence of current excessive alcohol consumption or drug dependence.
7. Participant has uncontrolled, clinically significant renal disease manifested by 1.5 \* ULN of serum creatinine or blood urea nitrogen (BUN) levels.
8. Participant has calculated creatinine clearance level of \<60 mL/min

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline (Day 1) up to follow-up (24.5 months)
measure: Number of Participants Who Prematurely Discontinued Treatment
timeFrame: Baseline up to Month 24
measure: Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities
timeFrame: Baseline up to follow-up (24.5 months)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline, up to follow-up visit (Month 24.5)
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Gastroenterology Associates
state: Alabama
city: Fayetteville
country: United States
facility: First Care Family Doctors South
state: Arkansas
city: Little Rock
country: United States
facility: Little Rock Diagnostic Clinic
state: Arkansas
city: Anaheim
country: United States
facility: AGMG Clinical Research
state: California
city: Beverly Hills
country: United States
facility: Lovelace Scientific Resources
state: California
city: Garden Grove
country: United States
facility: Digestive Liver Disease Specialists, Medical Group
state: California
city: Long Beach
country: United States
facility: Long Beach VA Medical Center
state: California
city: Orange
country: United States
facility: Community Clinical Trials
state: California
city: San Francisco
country: United States
facility: Rider Research Group
state: California
city: San Rafael
country: United States
facility: John Jolley, M.D.
state: California
city: Santa Ana
country: United States
facility: Lovelace Scientific Resources
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Clinical Research
state: California
city: Littleton
country: United States
facility: Professionals for Clinical Research
state: Colorado
city: Bristol
country: United States
facility: Connecticut Gastroenterology Institute
state: Connecticut
city: Brooksville
country: United States
facility: Clinical Research of Tampa Bay, Inc.
state: Florida
city: Hialeah
country: United States
facility: Medical Research Unlimited
state: Florida
city: Hollywood
country: United States
facility: Southern Clinical Research Consultants
state: Florida
city: New Smyrna Beach
country: United States
facility: United Medical Research
state: Florida
city: North Miami Beach
country: United States
facility: Venture Research Institute, LLC
state: Florida
city: Ormond Beach
country: United States
facility: Penninsula Research, Inc.
state: Florida
city: Palm Harbor
country: United States
facility: Advanced Gastroenterology Associates
state: Florida
city: Sarasota
country: United States
facility: Lovelace Scientific Resources
state: Florida
city: Sarasota
country: United States
facility: Advent Clinical Research
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute, Inc.
state: Florida
city: Atlanta
country: United States
facility: Consultative Gastroenterology
state: Georgia
city: Austell
country: United States
facility: Digestive Care Associates
state: Georgia
city: Decatur
country: United States
facility: Center for Gastroenterology
state: Georgia
city: Macon
country: United States
facility: Gastroenterology Associates of Central Georgia
state: Georgia
city: Arlington Heights
country: United States
facility: Northwest Gastroenterologists S.C.
state: Illinois
city: Waterloo
country: United States
facility: Covenant Clinic
state: Iowa
city: Topeka
country: United States
facility: Cotton-O'Neil Digestive Health Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Sinai Medical Office Building
state: Maryland
city: Hollywood
country: United States
facility: Philip J. Beam Medical Center
state: Maryland
city: Chesterfield
country: United States
facility: Research Institute of Michigan, LLC
state: Michigan
city: Mexico
country: United States
facility: Center for Digestive & Liver Diseases
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Center for Clinical Research
state: Missouri
city: Ocean City
country: United States
facility: Shore Health Group
state: New Jersey
city: New York
country: United States
facility: Simon Lichtiger, M.D.
state: New York
city: Northport
country: United States
facility: VA Medical Center, Northport
state: New York
city: Syracuse
country: United States
facility: VA Medical Center
state: New York
city: Troy
country: United States
facility: Upstate Gastroenterology Associates, PC
state: New York
city: Greensboro
country: United States
facility: LeBauer Research Associates, PA
state: North Carolina
city: High Point
country: United States
facility: Bethany Medical Center
state: North Carolina
city: Rocky Mount
country: United States
facility: Boice-Willis Clinic
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants for Clinical Research, Inc.
state: Ohio
city: Warren
country: United States
facility: Avamar Center for Endoscopy
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Gastroenterology Associates, LLC
state: Oklahoma
city: Charleston
country: United States
facility: Charleston Gastroenterology Specialists, LLC
state: South Carolina
city: Simpsonville
country: United States
facility: Hillcrest Clinical Research, LLC
state: South Carolina
city: Nashville
country: United States
facility: Medical Research Institute
state: Tennessee
city: Houston
country: United States
facility: NationsMed Clinical Research
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Houston
country: United States
facility: Houston Digestive Disease Clinic
state: Texas
city: Chesapeake
country: United States
facility: Gastroenterology Associates of Tidewater
state: Virginia
city: Christiansburg
country: United States
facility: New River Research Institute
state: Virginia
city: Seattle
country: United States
facility: Seattle Gastroenterology Associates
state: Washington
city: Spokane
country: United States
facility: Eastern Washington Clinical Research Center
state: Washington
city: Spokane
country: United States
facility: Spokane Digestive Disease Center
state: Washington
city: Tacoma
country: United States
facility: Digestive Disease Research Center
state: Washington
city: Milwaukee
country: United States
facility: Center for Advanced Research
state: Wisconsin
Study officials:
affiliation: Bausch Health Americas, Inc.
name: Lindsey Mathew
role: STUDY_DIRECTOR
References:
citation: Lichtenstein GR, Gordon GL, Zakko S, Murthy U, Sedghi S, Pruitt R, Barrett AC, Bortey E, Paterson C, Forbes WP. Long-Term Benefit of Mesalamine Granules for Patients Who Achieved Corticosteroid-Induced Ulcerative Colitis Remission. Dig Dis Sci. 2016 Jan;61(1):221-9. doi: 10.1007/s10620-015-3866-7. Epub 2015 Nov 12.