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Efficacy and Safety Study of MAX-002 Suppository Versus Placebo and Active Medicine in Mild to Moderate Ulcerative Proctitis

Phase 3
Terminated
Conditions
Proctitis, Ulcerative
Interventions
Registration Number
NCT01016262
Lead Sponsor
Forest Laboratories
Brief Summary

This is a prospective, multicenter, double-blind (DB), controlled, randomized, parallel group comparison Phase 3a study to evaluate the efficacy and safety of new mesalamine suppositories (MAX-002) as compared to placebo and active medicine after 6 weeks of treatment in adults with mild to moderate ulcerative proctitis (UP).

Detailed Description

The present study consists of screening period (2 weeks before randomization), DB phase (6 weeks), OL phase (8 weeks) and follow-up visits at Week 3, Week 6 and Week 14. Participants who are eligible will be randomized to receive 1g MAX-002, 1g Canasa® and placebo suppository once daily in the DB phase. Participants who complete or discontinue the study at Week 6 will either receive 1g MAX-002 suppositories on a voluntary basis, standard care treatment as per investigator's discretion or no treatment during the next 8 weeks of the OL phase. Total duration of treatment will be of 14 weeks. Efficacy will primarily be evaluated by percentage of participants who show response as per Mayo DAI Score at Week 6. Participants' safety will be monitored throughout the study.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
119
Inclusion Criteria
  • Participants who are 18 years old or older
  • Participants with total Mayo DAI score between 5 to 10 at Screening and participants with score of 2 or more for the rectal bleeding and for the findings of flexible proctosigmoidoscopy or colonoscopy sub-scores of the Mayo DAI
  • Participants with confirmed mild to moderate active UP not extending above rectum as evidenced by flexible proctosigmoidoscopy and histopathology assessments
  • Female participants of child-bearing age who have negative serum beta-human chorionic gonadotropin (β-HCG) at the time of entry into the study
  • Female participants of child-bearing age who use medically acceptable form of birth control
  • Participants who are smokers and non-smokers must not change their smoking habits or nicotine use during the DB treatment period
  • Participants who are literate and have legal ability to sign informed consent form
Exclusion Criteria
  • Participants with other digestive diseases interfering with the measurement of any sub-score of the Mayo DAI
  • Participants with known presence or suspicion of malignant disease of the digestive system or presence or history of neoplasms other than carcinoma in situ of the cervix or basal carcinoma of the skin
  • Participants with clinically significant electrocardiographic abnormalities that would compromise its participation in the study
  • Participants who are chronically using oral 5-aminosalicylic acid (5-ASA) at a dose greater than 4g daily, change in the oral 5-ASA dosing, or use of any form of rectal 5-ASA formulations during the 30 days prior to randomization
  • Participants with significant use of corticosteroids ,immunosuppressant's or biologic response modifiers that may have a therapeutic effect on ulcerative proctitis during the 45 days before the date of consent
  • Participants who use any rectally administered medicine during the 30 days prior to randomization
  • Participants who have contraindication to the use of mesalamine or suppository vehicle, analgesia, flexible proctosigmoidoscopy or colonoscopy
  • Participants who have blood parameters of grade 3 or higher on the common terminology criteria for adverse events (CTCAE) 5-point scale
  • Participants with severe renal or hepatic impairment with parameters of grade 3 or higher on the CTCAE
  • Participants with clinically significant urinary tract obstruction and history of idiopathic pancreatitis
  • Participants with presence of other known clinically significant medical and/or psychological illnesses precluding participation
  • Participants who participate in clinical studies other than observational studies during the 90 days before the date of the informed consent form signature
  • Participants who are unable or unwilling to complete the follow-up evaluations required for the study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MAX-002MAX-002-
PlaceboPlacebo-
Canasa®Canasa®-
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Who Were Responders at Week 6Week 6

Participants were considered as responders if they had total Mayo Disease Activity Index (DAI) score less than 3 points and no individual sub-scores greater than or equal to 2. Mayo DAI is a semi-quantitative scale which consists of 4 sub-scales: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy or colonoscopy and physician global assessment, each sub-scale ranged from 0 to 3 (0=normal, 3=severe). The total Mayo DAI score ranges from 0 (normal or inactive disease) to 12 (severe disease).

Secondary Outcome Measures
NameTimeMethod
Time to Relief of Rectal BleedingDay 1 up to Week 6

Time to relief of rectal bleeding was defined as number of days from randomization (Day 1) up to the first date of 3 consecutive days without observation of rectal bleeding during the double-blind phase.

Time to Relief of TenesmusDay 1 up to Week 6

Time to relief of tenesmus (feeling of constantly needing to pass stools, even if the bowels are already empty) was defined as the number of days from randomization (Day 1) up to the first date of 3 consecutive days without observation of tenesmus during the double-blind phase.

Percentage of Participants Who Were Responders at Week 3Week 3

Participants considered as responders if they had total Mayo DAI score less than 3 points and no individual sub-scores greater than or equal to 2. Mayo DAI is a semi-quantitative scale which consists of 4 sub-scales: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy or colonoscopy and physician global assessment, each sub-scale ranged from 0 to 3 (0=normal, 3=severe). The total Mayo DAI score ranges from 0 (normal or inactive disease) to 12 (severe disease).

Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6Baseline, Week 6

The IBDQ is used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 domains of wellness: bowel symptoms (10 questions), systemic symptoms (5 questions), social symptoms (5 questions) and emotional function (12 questions). The response to each question is graded on 7-point likert scale, ranging from 1 (worst aspect) to 7 (best aspect). The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score ranges from 32 to 224 with higher scores indicating a better quality of life.

Trial Locations

Locations (39)

Advanced Pain Care Clinic

🇺🇸

Evansville, Indiana, United States

MEDICOR - Centrum Medyczne

🇵🇱

Rzeszow, Poland

Szpital Kolejowy

🇵🇱

Pruszków, Poland

Gabinet Lekarski LECHMED

🇵🇱

Warszawa, Poland

Endoskopia SP. Z o.o.

🇵🇱

Sopot, Poland

Wojewodzki Szpital Specjalistyczny

🇵🇱

Lublin, Poland

SP Szpital Kliniczny

🇵🇱

Lublin, Poland

SPZOZ Uniwersytecki Szpital Kliniczny

🇵🇱

Lodz, Poland

Digestive Health Specialists of the Southeast

🇺🇸

Dothan, Alabama, United States

Toronto Digestive Disease Associates Inc. (TDDA)

🇨🇦

Vaughan, Ontario, Canada

Birmingham Gastroenterology Associates P.C.

🇺🇸

Birmingham, Alabama, United States

Wisconsin Center for Advanced Research

🇺🇸

Milwaukee, Wisconsin, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Desert Sun Gastroenterology

🇺🇸

Tucson, Arizona, United States

Rocky Mountain Gastroenterology Associates

🇺🇸

Thornton, Colorado, United States

Shafran Gastroenterology Center

🇺🇸

Winter Park, Florida, United States

Litchfield County Gastroenterology and Associates

🇺🇸

Torrington, Connecticut, United States

Clinical Research of South Florida

🇺🇸

Boynton Beach, Florida, United States

Digestive Research Associates

🇺🇸

Newnan, Georgia, United States

South Jersey Gastroenterology

🇺🇸

Marlton, New Jersey, United States

Center for Digestive & Liver Diseases Inc.

🇺🇸

Mexico, Missouri, United States

Synergy First Medical

🇺🇸

Brooklyn, New York, United States

Gastrointestinal Associates

🇺🇸

Jackson, Mississippi, United States

Research Associates of New York (RANY)

🇺🇸

New York, New York, United States

Consultants for Clinical Research

🇺🇸

Cincinnati, Ohio, United States

The First Clinic

🇺🇸

Nashville, Tennessee, United States

Surrey GI Clinic Research

🇨🇦

Guelph, Ontario, Canada

South Texas Research Alliance

🇺🇸

Laredo, Texas, United States

St-Joseph's Healthcare Hamilton

🇨🇦

Hamilton, Ontario, Canada

Hôpital Maisonneuve-Rosemont

🇨🇦

Montreal, Quebec, Canada

DHC Research

🇨🇦

Richmond Hill, Ontario, Canada

Alpha Recherche Clinique

🇨🇦

Quebec, Canada

GASTROMED s.c.

🇵🇱

Bialystok, Poland

Wojewódzki Szpital Specjalistyczny Oddz. Gastroenterologii

🇵🇱

Czestochowa, Poland

Gastroenterology Group of Naples

🇺🇸

Naples, Florida, United States

Center for Gastrointestinal Disorders

🇺🇸

Hollywood, Florida, United States

Memphis Gastroenterology Group

🇺🇸

Germantown, Tennessee, United States

Gastroenterology & Hepatology Clinic

🇨🇦

Abbotsford, British Columbia, Canada

Diamond Health Care Centre

🇨🇦

Vancouver, British Columbia, Canada

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