Clinical trial NCT01172444: Clinical Trial With Mesalamine 1g Suppositories
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Proctitis
Keywords: Mild to Moderate Ulcerative Proctitis
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
First posted: 2010-07-29
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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 27. Previous randomization in this study

Primary outcomes:
measure: DAI Score
timeFrame: 6 Weeks
Secondary outcomes:
measure: DAI Score, Improvement, Remission & Histological Disease Activity Score
timeFrame: 3 and 6 Weeks
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: Kamineni Hospitals, 4-1-1227, King Koti Road, Abids
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Nizam's Instiute of Medical Sciences, Department of Gastroenterology
state: Andhra Pradesh
city: Vijayawada
country: India
facility: Andhra Hospitals
state: Andhra Pradesh
city: Vijayawada
country: India
facility: Nagarjuna Hospitals Limited
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Manikya Institute of Gastroenterology and Hepatology, MVV Chambers,203,204
state: Andhra Pradesh
city: Guwahati
country: India
facility: Institute of Digestive and Liver Diseases
state: Assam
city: Arera Colony
country: India
facility: Global Liver & Gastroenterology Centre, E-5/24, Opp Arera Petrol Pump
state: Bhopal
city: Sheikhpura, Patna
country: India
facility: Indira Gandhi Institute of Medical Sciences
state: Bihar
city: Ahmedabad
country: India
facility: Department of Gastroenterology, Sheth V. S. General Hospital
state: Gujarat
city: Ahmedabad
country: India
facility: Ratandeep Surgical Hospital & Endoscopy Clinic
state: Gujarat
city: Ahmedabad
country: India
facility: Dr. Bhatnagar's Clinic
state: Gujarat
city: Ahmedabad
country: India
facility: Apollo Hospital International Ltd.
state: Gujarat
city: Rajkot
country: India
facility: Gastro Care Clinic
state: Gujarat
city: Surat
country: India
facility: Gastro Care
state: Gujarat
city: Bangalore
country: India
facility: Gokula Metropolis Clinical Research Center, M.S.Ramaiah Memorial Hospital, New BEL Road, MSRIT Post
state: Karnataka
city: Cochin
country: India
facility: PVS Memorial Hospital
state: Kerala
city: Thiruvanathapuram
country: India
facility: Sree Gokulam Medical College and Research Foundation
state: Kerala
city: Indore
country: India
facility: Gut- N-Hepa Care
state: Madhya Pradesh
city: Pune
country: India
facility: KEM Hospital & Research Centre, Department of Surgery
state: Maharashtra
city: Ramdaspeth
country: India
facility: Midas Institute of Gastroenterology
state: Nagpur
city: Chandigarh
country: India
facility: Department of Gastroentrology, Postgraduate Institute of Medical Education & Research
state: Punjab
city: Jaipur
country: India
facility: Dr. Nijhawan's Clinic
state: Rajasthan
city: Jaipur
country: India
facility: Sharma Gastroenterology Centre
state: Rajasthan
city: Jodhpur
country: India
facility: Kala Endoscopy & Liver Clinic
state: Rajasthan
city: Madurai
country: India
facility: Apollo Speciality Hospitals, Lake View Road, K. K. Nagar
state: Tamil Nadu
city: Alambagh, Lucknow
country: India
facility: Ajanta Hospital and IVF Center 765, ABC Complex , Kanpur Road
state: Uttar Pradesh
city: Lucknow
country: India
facility: C.S.M Medical University, Department of Surgical Gastroenterology, New Surgical Block (NSB)
state: Uttar Pradesh
city: Noida
country: India
facility: Dept. of Gastroenterology, Fortis Hospital, B-22, Sector-62
state: Uttar Pradesh
city: Ravindrapuri
country: India
facility: Samvedna Hospital, B 27/88G, New Colony
state: Varanasi
city: Ahmedabad
country: India
facility: Anand Multispeciality Hospitals Pvt Ltd, White house, Opp Rajasthan Hospital,Shahibaug
city: Hyderabad
country: India
facility: Leads Medical Center, First Floor, Ozone Complex
city: Hyderabad
country: India
facility: Dept. of Gastroenterology & Hepatology, Deccan College of Medical Sciences,Owaisi Hospital & Research Centre
city: Jaipur
country: India
facility: RAI Speciality Care Centre
city: Kolkata
country: India
facility: School of Digestive and Liver Diseases, IPGME&R
city: Nagpur
country: India
facility: Gastroenterology and Endoscopy Center
city: New Delhi
country: India
facility: Senior Consultant-Gastroenterology and Hepatology, Indraprastha Apollo Hospitals
city: Secunderabad
country: India
facility: Krishna Institute of Medical Sciences Ltd
city: Surat
country: India
facility: Liver Clinic
Study officials:
References: