A placebo controlled clinical trial to evaluate safety and efficacy of two doses of AM 3301 for add-on treatment of mild to moderate active ulcerative colotis
Scientific Title of Study
Multi-center, randomized, double-blind, placebo-controlled study of two dosages of AM3301 for add-on treatment of mild to moderate active ulcerative colitis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
KP 402
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Sivakumar S
Designation
Affiliation
Address
Kemin Pharma, A Division of Kemin Industries South Asia Pvt. Ltd, The Trapezium, No. 39, Second Floor, Nelson Manickam Road Chennai TAMIL NADU 600029 India
Phone
044-42202800
Fax
044-42202870
Email
sivakumar.s@kemin.com
Details of Contact Person Scientific Query
Name
Dr. V.T. Sriraam
Designation
Affiliation
Senior Manager, Medical Affairs
Address
Kemin Pharma, A Division of Kemin Industries South Asia Pvt Ltd, The Trapezium, No. 39, Second Floor, Nelson Manickam Road Chennai TAMIL NADU 600029 India
Phone
044 -32472446
Fax
044-42202870
Email
sriraamvt@aurovillehealthcare.com
Details of Contact Person Public Query
Name
D. Ahmed Meeran
Designation
Affiliation
Address
Kemin Pharma, A Division of Kemin Industries South Asia Pvt Ltd, The Trapezium, No. 39, Second Floor, Nelson Manickam Road Chennai TAMIL NADU 600029 India
Kemin Pharma, A Division of Kemin Industries South Asia Pvt Ltd,
The Trapezium, No. 39, Second Floor, Nelson Manickam Road
Chennai
TAMIL NADU
600029
India
Choithram Hospital and Research Centre, Manik Bagh Road, Indore-452014, Madhya Pradesh, India, Ph-0731-236249, ID.ajayvjain@yahoo.com, Fax-0731-2470068
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Dr. Ajit Sood
Dayanand Medical College & Hospital, Tagore Nagar, Civil Lines, Ludhiana-141001, Punjab, India, Ph-0161-2301749, ID.ajitsood10@sify.com, Fax-0161-2300791
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Dr. Mhd Aejaz Habeeb
Department of Gastroenterology and Hepatology, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad-500058, Andhra Pradesh, India, Ph-040-24342954, ID.aejazhabeeb@hotmail.com, Fax-040-24342954
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Dr. Rajesh Patil
Department of Surgery, Faculty Block Next to Library, Goa Medical College, Bambolim, Goa-403202, India, Ph-0832-2495275, ID.dr.rpatil@rediffmail.com, Fax-0832-2458728
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Dr. Abhijit Chandra
Department of Surgical Gastroenterology, Chhatrapati Shahuji Maharaja Medical University, Lucknow-226003, Uttar Pradesh, India, Ph-0522-2258660, ID.abhijitchandra@hotmail.com, Fax-0522-2258982
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Dr. Sandeep Nijhawan
Dr. Sandeep Nijhawan Clinic, 112, Panchsheel Enclave, Gokul Bhai Bhatt Marg, Durgapura, Jaipur-302017, Rajasthan, India, Ph-9829272233, ID.nijhawan@yahoo.com, Fax-0141-2575466
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Dr. Chetan Mehta
Gastro Care Clinic, Karansinhji Main Road, Opposite to Dr. Bharat Parekh Hospital, Rajkot-360001, Gujarat, India, Ph-0281-2235010, ID.mehtacn@hotmail.com, Fax-0281-2232112
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Dr. Deval Parikh
Jagmohan Hospital, Behind Old High Court, Navrangpura, Ahmedabad-380009, Gujarat, India, Ph-9824026626, ID.drdevalparikh@gmail.com, Fax-079-27545111
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Dr. Rajiv Mehta
Liver Clinic 203-204, Narmada Complex, Near Kadiwala School, Ring Road, Surat-395002, Gujarat, India, Ph-0261-2464290, ID.rmgastro@yahoo.com, Fax-0261-2464296
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Dr. Rajiv Kumar Shrivastava
Nagarjuna Hospital, Kanuru, Vijayawada-520007, Andhra Pradesh, India, Ph-9866131741, ID.rajshri73@yahoo.co.in, Fax-0866-2554169
Samvedana Hospital, B-27/88G New Colony, Ravindra Puri, Varanasi-221005, Uttar Pradesh, India, Ph-0542-2420456, ID.hemantg26@yahoo, Fax-0542-2277629
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Dr. Ravi Shankar
Yashoda Hospitals, Hari Hara Kala Bhavan, S.P. Road, Secunderabad-500003, Andhra Pradesh, India, Ph-040-27713333, ID.b_ravishankar@yahoo.com, Fax-040-277039999
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Details of Ethics Committee
No of Ethics Committees= 14
Name of Committee
Approval Status
Dr Ashish Sethi - Vadodara Ethics Committee
Approved
Dr Chetan Mehta - Independent Ethics Committee
Approved
Dr Deval Parikh - Sukhmani Ethics Committee
Approved
Dr. Abhijit Chandra
Submittted/Under Review
Dr. Ajaykumar Jain - Choithram Hospital and Research Centre Ethics Committee
Approved
Dr. Ajit Kukreja - Sukhmani Ethics Committee
Approved
Dr. Ajit Sood - Dayanand Medical College and Hospital Institutional Ethics Committee
Submittted/Under Review
Dr. Hemant Gupta - Samvedna Hospital Ethics Committee
Approved
Dr. Mhd Aejaz Habeeb - Institutional Ethics Committee
Approved
Dr. Rajesh Patil - Goa Medical College and Hospitals Local Ethics Committee
Approved
Dr. Rajiv Kumar Shrivastava - Nagarjuna Hospital Ethics Committee
Approved
Dr. Rajiv Mehta - Heart First Ethics Committee
Approved
Dr. Ravi Shankar - Yashoda Academy of Medical Education and Research Institutional Ethics Committee
Approved
Dr. Sandeep Nijhawan - Sanjeevani Ehics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Mild to moderate ulcerative colitis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
AM 3301
100 mg BD
Intervention
AM3301
200 mg bid
Comparator Agent
Placebo
bid
Inclusion Criteria
Age From
Age To
Gender
Details
1. Must sign and date written informed consent prior to any study-related procedures and, in the opinion of the investigator, be willing and likely to comply with all requirements of the study
2. Male or non-pregnant female subjects 18-65 years of age, inclusive
3. A history of UC for at least 6 months prior to screening
4. All subjects must have clinical and endoscopic confirmed diagnosis of active mild to moderate UC with disease extension beyond the rectum (>12 cm from the ano-rectal junction):
5. Confirmed by obligatory colonoscopy/ endoscopy at screening: full report to be available and score >2 (at least moderate friability)
6. Ulcerative Colitis Disease Activity Index [UCDAI] of 5-10, inclusive, as assessed on screening (based on retrospective recall by the subject over the previous 3 days) and to be confirmed after 7 days of baseline observation, before inclusion in the randomization procedure, and not improving ≥2 score points during the baseline period
7. Duration of current relapse less than 6 weeks from screening (according to subject)
8. Oral mesalazine/sulfasalazine maintenance therapy (<2g/day) for no less than 30 days prior to screening
9. Females of childbearing potential require a negative urine pregnancy test and must agree to abstinence or to use prescription contraceptives and to use a barrier contraceptive device along with a spermicidal product for the duration of the study. Subjects who are surgically sterile, menopausal or using contraceptive implants prior to the study enrolment are not required to utilize dual contraceptive techniques
10. Otherwise in generally good health as judged by the investigator
ExclusionCriteria
Details
1. Proctitis (<12 cm from the ano-rectal junction)
2. Indeterminate colitis
3. Crohn?s disease
4. Previous colonic surgery
5. Severe or fulminant UC [UCDAI >10] or requiring hospitalization
6. Evidence of other forms of inflammatory bowel disease
7. Subjects with a new diagnosis of UC
8. Subjects who altered their mesalazine/sulfasalazine dosage (dose regimen or dose) in the 2 weeks prior to screening
9. Subjects with a positive stool culture for any enteric pathogens that is clinically significant, pathogenic ova or parasites, or a positive EIA that is subsequently confirmed by a positive cytotoxin assay for C. difficile toxin
10. Subjects who have used the following medications within the specified period
a. Loperamide and other anti-diarrheal agents, probiotics, antibiotics: 1 week during run-in period
b. NSAIDs and COX-2 inhibitors, within 14 days from screening
c. Oral and injectable steroids, within 30 days from screening
d. Rectally administered mesalazine/sulfasalazine or other 5-ASAs or steroids, within 7 days from screening. Topical medications except for suppository and enemas are not excluded
e. Antivirals or antifungals within 30 days
f. Immunomodulating/suppressing drugs or biologicals (including anti TNF-α, cyclosporine, thalidomide, methotrexate) within 2 months
g. Sulfasalazine/mesalazine at higher dose than for maintenance treatment (higher than 2 g/day) within 30 days
11. Failing to respond to steroids within the previous year prior to screening
12. Subjects who have any other clinically significant disease(s) which, in the opinion of the investigator, could compromise the subject?s involvement in the study or overall interpretation of the data, such as mental/emotional disorder, dysplasia or cancer, seropositivity for HIV, HCV, uncontrolled hematologic, renal, hepatic, metabolic pulmonary or cardiovascular disease and active alcohol or drug abuse
13. Needing enemas to treat their disease or to maintain remission
14. Subjects with abnormal laboratory values at admission which are clinically significant by the investigator (outlier values outside the normal values are allowed and to be marked as ?NCS? if considered Not Clinically Significant (NCS) by the investigator based on the nature of the disease. Quite some UC subjects have an aberrant immune response and abnormal laboratory values due to the impaired absorption, and blood loss
15. Subjects whose UCDAI score decreases ≥2 during the 7-day run-in period
16. Allergy to aspirin or salicylate derivatives
17. Subject with a history of drug allergy in general or hypersensitivity to anti-inflammatory drugs
18. Participation in another clinical study within the last 3 months prior to screening
19. Inability to comply with the protocol requirements or to fill in the diary cards
20. Pregnancy or breast-feeding women or women of child-bearing potential not agreeing to birth control
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
Change from baseline in UCDAI score after 8 weeks.
at 8 weeks i.e. visit 3
Secondary Outcome
Outcome
TimePoints
Change from baseline in partial UCDAI score.
at week 2 (visit 1), week 4 (visit 2) and week 8 (visit 3)
Proportion of subjects in remission
at week 8 and at end of treatment
Proportion of subjects with clinical response
2nd, 4th and 8th week
Disease specific quality of life
2nd 4th and 8th week
Safety
2nd, 4th and 8th week
Time to remission and number of treatment failures
At end of study
Target Sample Size
Total Sample Size="180" Sample Size from India="" Final Enrollment numbers achieved (Total)= "" Final Enrollment numbers achieved (India)=""
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This study is multicentric, randomized, double blind placebo controlled study to evaluate two dosages of AM 3301 for add-on treatment of mild to moderate active ulcerative colitis.A total 180 subjects will be enrolled and randomized to 3 treatment arms in 1:1:1 ratio. Primary endpoint would be change from baseline UCDAI score to week 8 UCDAI score. In addition disease specific Quality of life and safethy of the study medication would be evaluated. The run in period is of 1 week and treatment period is of 8 weeks. The anticipated date of enrollment is 1st June 2010.