Clinical Trial With Mesalamine 1g Suppositories

• Sponsor: Sandoz (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01172444
• Collaborator: (none)
• Enrollment: 158
• Locations: 38
• Arms: 3
• Duration (Months): 30
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Proctitis	Drug: Mesalamine; Drug: Canasa; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 158 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• 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 Start Date: Jun 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. DAI Score [6 Weeks]

   Mean difference in the DAI score between Baseline and the Final Visit.

Secondary Outcome Measures

1. DAI Score, Improvement, Remission & Histological Disease Activity Score [3 and 6 Weeks]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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
2. 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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Sandoz

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT01172444
• Other Study ID Numbers: MESA-ULP3125
• First Posted: Jul 29, 2010
• Last Update Posted: Mar 27, 2017
• Last Verified: Jul 1, 2015

• Keywords provided by Sandoz: Mild to Moderate Ulcerative Proctitis
• Additional relevant MeSH terms: Proctitis; Mesalamine

Study Results

No Results Posted as of Mar 27, 2017