AN INVESTIGATOR-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO ESTABLISH THERAPEUTIC EQUIVALENCE OF 1000 mg MESALAMINE RECTAL SUPPOSITORIES AND CANASA® RECTAL SUPPOSITORIES (1000 mg MESALAMINE, USP) IN THE TREATMENT OF MILD TO MODERATE ULCERATIVE PROCTITIS
1. Adults, male and female, 18 to 65 years of age
2. Active, mild to moderate UP, with disease activity not to exceed 15 cm beyond the anal verge: the upper disease boundary will be confirmed by flexible sigmoidoscopy/colonoscopy performed within 14 days of the Baseline Visit
3. Newly diagnosed or newly relapsed UP, where newly relapsed UP is defined as UP that has relapsed within less than and equal to 6 weeks prior to the Baseline Visit
4. A Disease Activity Index (DAI) score greater than or equal to 4 and less than or equal to 10 at the Baseline Visit; the DAI must include a Physician's Global Assessment (PGA) sub-score of less than or equal to 2, a rectal bleeding sub-score of greater than or equal to 1 and a mucosal appearance sub-score of greater than or equal to 1
5. Histological confirmation of UP with a Histological Disease Activity Score > or equal to 1 for the biopsy taken from the most severe area of disease during the flexible sigmoidoscopy/colonoscopy performed within 14 days of the Baseline Visit
6. For female patients of child-bearing potential, a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit; all female patients will be considered of child-bearing potential unless they are post-menopausal for at least one year or have been surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy)
7. Female patients of childbearing potential must be practicing one of the following methods of birth control and must agree to continue with regimen throughout the study: hormonal methods such as oral, implantable, injectable, or transdermal contraceptives for a minimum of one full cycle (based on the patient's usual menstrual cycle period) before investigational product administration; total abstinence from sexual intercourse (since the last menses before investigational product administration); intrauterine device; double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream); Male patients must also agree to use acceptable methods of birth control with their female partners, and this may include use of a male condom plus spermicide.
8. Ability to give written informed consent
9. Ability and willingness to comply with study requirements, including dosing procedures, diary completion, and study visits
ExclusionCriteria
Details
1. Known history of allergic reaction or clinically significant intolerance to aspirin or salicylate derivatives (including mesalamine) or non-active ingredients of the investigational product
2. Onset of UP relapse >6 weeks prior to the Baseline Visit for patients experiencing a relapse of their UP (i.e., patients who are not newly diagnosed)
3. Severe UP as defined by a DAI score of greater than or equal to 11 or a PGA sub-score of 3
4. Histological Disease Activity Score > or equal to 1 for the biopsy taken from the normal tissue above the disease margin during the flexible sigmoidoscopy/colonoscopy performed within 14 days of the Baseline Visit
5. UP with disease involvement greater than 15 cm beyond the anal verge as confirmed on flexible sigmoidoscopy/colonoscopy
6. Prior unsuccessful treatment of active UP or active ulcerative colitis with rectally administered mesalamine preparations of any strength
7. Any prior treatment of UP or ulcerative colitis with any oral 5-aminosalicylic acid product if used at >2 g/day, regardless of treatment outcome
8. Use of local, rectally administered therapies for UP or ulcerative colitis (e.g., suppositories or enemas containing mesalamine, etc.) within 30 days of the Baseline Visit
9. Use of any of the following medications:
- Biological therapies (e.g., infliximab) within 90 days of the Baseline Visit
- Immunosuppressive/immunomodulating (e.g., azathioprine) medications within 90 days of the Baseline Visit
- Oral, intravenous, intramuscular, or rectally administered corticosteroids within 30 days of the Baseline Visit; the use of intranasal and/or inhaled corticosteroids is permitted
- Oral 5-aminosalicylic acid products within 7 days of the Baseline Visit, if used at & less than or equal to 2 g/day
- Oral, intravenous, or intramuscular antibiotics within 7 days of the Baseline Visit
- Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) within 7 days of the Baseline Visit; low-dose aspirin (less than or equal to 325 mg/day) taken for cardio-protective reasons is permitted
- Antidiarrheals, antispasmodics, and iron therapy within 7 days of the Baseline Visit
- Transdermal nicotine products within 7 days of the Baseline Visit
10. A change in regimen (i.e., dosage or frequency of use) of permitted medications within 30 days of the Baseline Visit, or any plans to change the regimen during the course of this study
11. Use or treatment with an investigational drug, therapy, or device within 30 days of the Baseline Visit
12. A planned change in tobacco usage (e.g., smoking, oral tobacco) during the study
13. Female patients who are pregnant, planning a pregnancy, or who are breastfeeding
14. Diseases interfering with the DAI assessment, including but not limited to, hemorrhoids and anal fissures
15. History of Crohn Disease, short bowel syndrome, or bowel surgery (except appendectomy), or active peptic ulcer
16. A positive stool culture for enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Vibrio, E. coli O157/H7), detection of Clostridium difficile toxin through immunoassay, or enteric parasites and their ova (including Giardia, Cryptosporidium, and Entamoeba histolytica) on routine microscopy at the Screening Visit
17. Significant impairment of renal or hepatic function, as defined by any of the following:
- Creatinine >1.5 x Upper Limit Normal (ULN)
- Alanine Amino Transferase (ALT) >2.5 x ULN
- Aspartate Amino Transferase (AST) >2.5 x ULN
18. Serologic positivity for the Hepatitis B virus (HBV), the Hepatitis C virus (HCV), the Human Immunodeficiency Virus (HIV), or Treponema pallidum (the causative agent of syphilis)
19. Known history of idiopathic / chronic pancreatitis
20. History of active drug or alcohol abuse within the past year, or physical examination findings indicating the same
21. Current clinically significant urinary tract obstruction
22. History of coagulation disorders, including those requiring treatment with anticoagulant drugs (except for aspirin taken at ≤325 mg/day for cardio-protective reasons
23. Current active malignancy or history of malignancy within the past five years, except for cervical carcinoma in situ, squamous or basal cell carcinoma of the skin that has been surgically removed, or prostate cancer that is being managed by watchful waiting (observation alone)
24. History of pelvic irradiation
25. Any other clinically significant abnormal medical condition that in the Investigators judgment would put the patient at increased risk of illness or injury, would interfere with study participation or would interfere with the evaluation or quality of the data
26. Inability or unwillingness to understand and comply with the requirements of the protocol for any reason, including dosing procedures and visit requirements
• The mean difference in the DAI score between baseline and the Interim Visit
•The mean difference in scores for each of the individual DAI parameters (stool frequency, rectal bleeding, PGA, and mucosal appearance) between baseline, Interim Visit and the Final Visit
•Proportion of patients achieving an ?improvement?, where ?improvement? is defined as a ≥3 point improvement in overall DAI score, which will include a ≥1-point improvement in the rectal bleeding sub-score
3 and 6 weeks
Target Sample Size
Total Sample Size="533" Sample Size from India="" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
An Investigator-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Establish Therapeutic Equivalence of 1000 mg Mesalamine Rectal Suppositories and Canasa® Rectal Suppositories (1000 mg Mesalamine, USP) in the Treatment of Mild to Moderate Ulcerative Proctitis will be conducted in 533 patient with a estimated duration of 18months.