Clinical Trial With Mesalamine 1g Suppositories

Proctitis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01172444
• Other study ID #: MESA-ULP3125
• Status: Terminated
• Phase: Phase 3
• First received: July 28, 2010
• Last updated: March 22, 2017
• Start date: June 2010
• Est. completion date: December 2012

Study information

• Verified date: July 2015
• Source: Sandoz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 158
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Proctitis

Intervention

Drug:
• Mesalamine
Supporitory, Once Daily, Per Rectal for 6 Weeks
• Canasa
Suppository, Once Daily, Per Rectal for 6 Weeks
• Placebo
Suppository, Once Daily, Per Rectal for 6 Weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Sandoz

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DAI Score	Mean difference in the DAI score between Baseline and the Final Visit.	6 Weeks
Secondary	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