Clinical Trial With Mesalamine 1g Suppositories

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

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.

Study Overview

• Status: Terminated
• Conditions: Proctitis
• Intervention / Treatment: Drug: Mesalamine; Drug: Canasa; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Ahmedabad, India, 380004
    • Anand Multispeciality Hospitals Pvt Ltd, White house, Opp Rajasthan Hospital,Shahibaug
  • Hyderabad, India, 500 082
    • Leads Medical Center, First Floor, Ozone Complex
  • Hyderabad, India, 500058
    • Dept. of Gastroenterology & Hepatology, Deccan College of Medical Sciences,Owaisi Hospital & Research Centre
  • Jaipur, India, 342019
    • RAI Speciality Care Centre
  • Kolkata, India, 700020
    • School of Digestive and Liver Diseases, IPGME&R
  • Nagpur, India, 440012
    • Gastroenterology and Endoscopy Center
  • New Delhi, India, 110044
    • Senior Consultant-Gastroenterology and Hepatology, Indraprastha Apollo Hospitals
  • Secunderabad, India, 500003
    • Krishna Institute of medical sciences Ltd
  • Surat, India, 395002
    • Liver Clinic
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500 001
      • Kamineni Hospitals, 4-1-1227, King Koti Road, Abids
    • Hyderabad, Andhra Pradesh, India, 500 082
      • Nizam's Instiute of Medical Sciences, Department of Gastroenterology
    • Vijayawada, Andhra Pradesh, India, 520002
      • Andhra Hospitals
    • Vijayawada, Andhra Pradesh, India, 520007
      • Nagarjuna Hospitals Limited
    • Visakhapatnam, Andhra Pradesh, India, 530002
      • Manikya Institute of Gastroenterology and Hepatology, MVV Chambers,203,204
  • Assam
    • Guwahati, Assam, India, 781006
      • Institute of Digestive and Liver Diseases
  • Bhopal
    • Arera Colony, Bhopal, India
      • Global Liver & Gastroenterology Centre, E-5/24, Opp Arera Petrol Pump
  • Bihar
    • Sheikhpura, Patna, Bihar, India, 800014
      • Indira Gandhi Institute of Medical Sciences
  • Gujarat
    • Ahmedabad, Gujarat, India, 380006
      • Department of Gastroenterology, Sheth V. S. General Hospital
    • Ahmedabad, Gujarat, India, 380008
      • Ratandeep Surgical Hospital & Endoscopy Clinic
    • Ahmedabad, Gujarat, India, 380009
      • Dr. Bhatnagar's Clinic
    • Ahmedabad, Gujarat, India, 382428
      • Apollo Hospital International Ltd.
    • Rajkot, Gujarat, India, 360001
      • Gastro Care Clinic
    • Surat, Gujarat, India, 395002
      • Gastro Care
  • Karnataka
    • Bangalore, Karnataka, India, 560 054
      • Gokula Metropolis Clinical Research Center, M.S.Ramaiah Memorial Hospital, New BEL Road, MSRIT Post
  • Kerala
    • Cochin, Kerala, India, 682017
      • PVS Memorial Hospital
    • Thiruvanathapuram, Kerala, India, 695607
      • Sree Gokulam Medical College and Research Foundation
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452001
      • Gut- N-Hepa Care
  • Maharashtra
    • Pune, Maharashtra, India, 411011
      • KEM Hospital & Research Centre, Department of Surgery
  • Nagpur
    • Ramdaspeth, Nagpur, India, 440010
      • Midas Institute of Gastroenterology
  • Punjab
    • Chandigarh, Punjab, India, 160012
      • Department of Gastroentrology, Postgraduate Institute of Medical Education & Research
  • Rajasthan
    • Jaipur, Rajasthan, India, 302017
      • Dr. Nijhawan's Clinic
    • Jaipur, Rajasthan, India, 302021
      • Sharma Gastroenterology Centre
    • Jodhpur, Rajasthan, India, 342001
      • Kala Endoscopy & Liver Clinic
  • Tamil Nadu
    • Madurai, Tamil Nadu, India, 625020
      • Apollo Speciality Hospitals, Lake View Road, K. K. Nagar
  • Uttar Pradesh
    • Alambagh, Lucknow, Uttar Pradesh, India
      • Ajanta Hospital and IVF Center 765, ABC Complex , Kanpur Road
    • Lucknow, Uttar Pradesh, India, 226003
      • C.S.M Medical University, Department of Surgical Gastroenterology, New Surgical Block (NSB)
    • Noida, Uttar Pradesh, India, 20130
      • Dept. of Gastroenterology, Fortis Hospital, B-22, Sector-62
  • Varanasi
    • Ravindrapuri, Varanasi, India, 221005
      • Samvedna Hospital, B 27/88G, New Colony

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test; Sandoz Mesalamine 1 g Suppository	Drug: Mesalamine; Supporitory, Once Daily, Per Rectal for 6 Weeks
Active Comparator: Reference; Canasa 1 g Suppository	Drug: Canasa; Suppository, Once Daily, Per Rectal for 6 Weeks
Placebo Comparator: Placebo; Sandoz 1 g Placebo Suppository	Drug: Placebo; Suppository, Once Daily, Per Rectal for 6 Weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DAI Score	Mean difference in the DAI score between Baseline and the Final Visit.	6 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DAI Score, Improvement, Remission & Histological Disease Activity Score	The mean difference in the DAI score and each of the individual DAI parameters between Baseline, Interim and Final Visits; Proportion of patients achieving an "improvement", defined as a ≥3 point improvement in overall DAI score and the proportion of patients achieving a "remission", where "remission" is defined as a DAI score of 0-1 at the Interim and Final Visit.; The mean difference in the histological disease activity score between baseline and the Final Visit	3 and 6 Weeks

Collaborators and Investigators

• Sponsor: Sandoz

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: July 28, 2010
• First Submitted That Met QC Criteria: July 28, 2010
• First Posted (Estimate): July 29, 2010

Study Record Updates

• Last Update Posted (Actual): March 27, 2017
• Last Update Submitted That Met QC Criteria: March 22, 2017
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Mild to Moderate Ulcerative Proctitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Rectal Diseases; Proctitis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: MESA-ULP3125