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1 Clinical Trial Details (PDF Generation Date :- Thu, 04 Apr :39:30 GMT) CTRI Number Last Modified On 13/02/2019 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study CTRI/2016/03/ [Registered on: 02/03/2016] - Trial Registered Prospectively No Interventional Drug Single Arm Trial A clinical trial to study the safety of Esomeprazole and Levosulpiride for therapy of Gastroesophageal reflux disease (GERD) in patients Evaluation Of Safety And Efficacy Of Fixed Dose Combination Of Esomeprazole And Sustained Release Levosulpiride For Short Term Therapy Of Gastroesophageal Reflux Disease (GERD) In Patients Who Do Not Respond To PPI Alone: An Open Label, Multicentric Study Secondary IDs if Any Secondary ID Identifier Details of Principal Investigator or overall Trial Coordinator (multi-center study) Details Contact Person (Scientific Query) Details Contact Person (Public Query) SP/IP-123/0914 Version 03 Amendment 01 Dated 18/02/16 Designation Affiliation Protocol Number Details of Principal Investigator Dr Nomita Chatterjee Bhandari General Manager Phone Fax Designation Affiliation Sun Pharma Laboratories Limited,Sun House,Plot No. 201 B/1, Western Express Highway, Goregaon(E), Mumbai , Maharashtra, Mumbai nomita.bhandari@sunpharma.com Details Contact Person (Scientific Query) Dr Maulik Doshi Medical Monitor Phone Fax Designation Affiliation Sun Pharma laboratories Limited Sun Pharma laboratories Limited Tandalja, Vadodara Gujarat Mumbai maulik.doshi@sunpharma.com Details Contact Person (Public Query) Guruprasad Palekar Senior manager Sun Pharma laboratories Limited Sun Pharma Laboratories Limited Sun House, 201 B/1, Western Express Highway, Goregaon ( E),Mumbai Mumbai page 1 / 9

2 Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Sites of Study Phone Fax Source of Monetary or Material Support > Sun Pharma Laboratories Limited Sun House, 201 B/1, Western Express Highway, Goregaon ( E),Mumbai Type of Sponsor NIL List of Countries of Principal Investigator Dr Jagdish Bhagabhai Patel Dr Sanjay Deshpande Dr Darshana Makwana Dr Sumit Jain Dr Janak R Khambolja Primary Sponsor Details Sun Pharma Laboratories Limited Sun Pharma Laboratories Limited Sun House, 201 B/1, Western Express Highway, Goregaon ( E),Mumbai Pharmaceutical industry-n NIL of Site Site Phone/Fax/ Anand Multi Speciality Hospital Pvt.Ltd ASTER AADHAR HOSPITAL (Prerana Hospital Ltd.) B.J. Medical college & Civil Hospital B.Y.L Nair Charitable Hospital Mumbai central Dept. of Medicine, Smt. NHL MMC Sheth VS Gen. Hospital Anand Multi Speciality Hospital Pvt.Ltd., White House, Opp.Rajasthan Hospital, Shahibaug, Ahmedabad, Gujarat Room No 5, Ground floor,aster AADHAR HOSPITAL (Prerana Hospital Ltd.) R.S.No. 628, B Ward, Near Shastri Nagar, KMT Workshop, Kolhapur Maharashtra Kolhapur D-4, Department of Medicine, Asarwa, Ahmedabad , Gujarat Department of Gastroenterology, 7th floor OPD building Mumbai Mumbai Dept. of Medicine, Smt. NHL MMC Sheth VS Gen. Hospital campus, Ellisbridge, drjbpatel@hotmail.com m_darshana7@yahoo.c o.in sumit19sj@gmail.com kham_jak@yahoo.com page 2 / 9

3 Dr Ranjana G Deshmukh Dr. Hedgewar Hospital, Department of internal medicine Ahmedabad, , Gujarat Dr. Hedgewar Hospital, Department of internal medicine, Garkheda, Aurangabad Aurangabad Dr P Shravan Kumar Gandhi Hospital Department of Gastroenterology, R- 502, 5th floor Gandhi Hospital Department of Gastroenterology, Musheerabad, Secunderabad Hyderabad ANDHRA PRADESH Dr Vipul B Prajapati Dr Anumala Kavitha Dr Anupam Mandal Dr Kartik Vikrambhai Patel Dr Ramesh Kumar Gupta GCS Medical college Centre Guntur Government Hospital IPGME & R/SSKM hospital, Kanoria Hospital & Research centre Marudhar Hospital Department of Medicine, Opp D.R.M Office, Nr. Chamunda Bridge, Naroda Road, Ahmedabad , Gujarat Room No-220, Jubilee block, Guntur Government Hospital,Guntur, Andhra Pradesh, Guntur ANDHRA PRADESH Bamr.dhr@gmail.com shravangastro@gmail.c om prajapativipul1983@gm ail.com jananigastro@ymail.co m Department of Medicine, 4th Floor Ronald Ross Building Anupammondal89@gm Department of ail.com Medicine, 4th Floor Ronald Ross Building IPGME & R/SSKM hospital, 244, AJC Bose Road,Kolkata Kolkata WEST BENGAL Kanoria Hospital & Research centre, Airport-Gandhinagar Highway, Village: Bhat, Dist- Gandhinagar , Gujarat, Gandhinagar drkartikpatel1980@gma il.com Department of Medicine Marudhar Hospital A-93-99, Singh Bhoomi, dockrgupta128@gmail. Khatipura Road, Jaipur- com Rajasthan, page 3 / 9

4 Dr Rahul Kothari Dr Tarunendranath Lahiri Mazumdar Dr Prakash Harishchandra Kurmi P.D.E.A s Ayurved Rugnalay & Sterling Multispeciality, hospital Peerless Hospitex Center Limited Shivam Hospital & Diagnostic centre Jaipur RAJASTHAN P.D.E.As Ayurved Rugnalay & Sterling Multispeciality, hospital, Sector No. 27, Near Bhel Chowk, Nigdi Pradhikaran, Pune Maharashtra, Pune 1ST FLOOR, Peerless Hospitex Hospital & Research Center Limited 360, Panchasayar, Kolkata , Kolkata WEST BENGAL Shivam Hospital & Diagnostic centre, C/4 Satyanarayan society, Gor s Kuva, Near Jashodanagar cross road, Maninagar East, Ahmedabad- 8 Gujarat- DrShrihari Dhorepatil Shree Hospital R-03, 3rd floor, Department of Surgery Shree Hospital Siddharth Mansion, Opp Agakhan Palace, Nagar Road, Pune Maharashtra Pune Dr Sandeep Nijhawan Dr Narayan Sonaji Sonawane SMS Medical college & attached hospital Supe Heart & Diabetes Centre Dept of Gastroenterology, S.M.S. Medical College & attached hospital, J.L.N. Marg, Jaipur , Rajasthan, Jaipur RAJASTHAN R- 02,Department of Gastroenterology Supe Heart & Diabetes Centre Opposite Adharashram, Gharpura Ghat, Near Runghta High School, Ashokstambh, Nashik Maharashtra dr.rahulkothari11@gmai l.com tarun48@gmail.com dr_prakashkurmi@yaho o.com sdhorepatil@gmail.com dr_nijhawan@yahoo.co m drnarayansonawane@r ediffmail.com page 4 / 9

5 Details of Ethics Regulatory Clearance Status from DCGI Health Condition / Problems Studied Intervention / Comparator Agent Inclusion Criteria Nashik of Approval Status Date of Approval Is Independent Ethics? Aster Aadhar Ethics Dr. Babasaheb Ambedkar Medical Research societys Ethics committee Ethics Committe of Shree Hospital Ethics of S M S Medical College & attached Hospitals Ethics, Guntur Medical College & Government General Hospital Approved 11/01/2016 No Approved 24/06/2016 No Approved 12/01/2016 No Approved 04/07/2016 No Approved 11/03/2016 No Institutional Ethics, B.J.Medical College & CIVIL Hospital Approved 23/04/2016 No IPGME & R Research oversight Kanoria Ethics, Kanoria Centre Marudhar Hospital Ethics Shivam Ethics Sterling Hospital, Institutional Ethics Supe Hospital Ethics Status Approved 04/03/2016 No Approved 28/03/2016 No Approved 16/04/2016 No Approved 10/03/2016 No Approved 06/07/2016 No Approved 15/02/2016 No Date Approved/Obtained 03/12/2015 Health Type Patients Condition Gastro-esophageal reflux disease with esophagitis Type Details Comparator Agent NA NA Intervention Age From Age To Gender Details Fixed Dose Combination of Once daily for 4 weeks Route Esomeprazole 40mg and oral Levosulpiride SR 75 mg capsule Year(s) Year(s) Both Inclusion Criteria Patients must meet all of the following criteria to be considered for page 5 / 9

6 enrollment in the study: 1.Male or female patients aged between years. 2.Patients with known history of Gastro esophageal reflux disease (GERD) within last 03 months. 3.Patients who are on Proton pump inhibitor (PPI) alone since 4 weeks prior to screening and not adequately controlled. Minimum dose/day: Pantoprazole (40 mg), Esomeprazole (20 mg), Omeprazole (20 mg). Rabeprazole (20mg) and Lansoprazole (15 mg). 4.Patients willing to give informed consent. Exclusion Criteria Details Exclusion Criteria Patients meeting any of the following criteria must be excluded from enrollment in the study: 1.Pregnant, lactating women or women of childbearing age who are not using an acceptable method of birth control. 2.Patients with peptic ulcer or Zollinger-Ellison syndrome. 3.Patients with previous surgery of gastrointestinal tract excluding appendectomy, cholecystectomy and polypectomy. 4.Patients with other diseases or conditions such as scleroderma, pancreatitis, cancer, Parkinson s disease, epilepsy, mania and inflammatory bowel disease. 5.Patients with any severe illnesses (hepatic, renal, cardiac). 6.Patients with uncontrolled diabetes, hypertension, clotting disorder. 7.Heavy smokers (> 10 cigarettes per day in last 06 months). 8.History of hypersensitivity or known contraindication to either Pantoprazole or Levosulpiride. 9.Recent (in the past two years) drug dependence or abuse. 10.History of non-compliance to medical regimens or those patients unwilling to comply with the study protocol. Method of Generating Random Sequence Method of Concealment Blinding/Masking Not Applicable Not Applicable Open Label Primary Outcome Outcome Timepoints Proportion of participants with adverse events and serious adverse events Baseline, Day: 14, Day:28 Secondary Outcome Outcome Timepoints Change in Frequency Scale for the Symptoms of GERD Scale (FSSG) from baseline. Change in Severity of symptoms of GERD by Likert Scale from baseline Time frame:02 and 04 weeks Time frame: 02 and 04 weeks Time frame: 02 and 04 weeks Clinical Global Impression of Improvement (CGI-I) Clinical Global Impression of Severity (CGI-S) Time frame: Day-0 and 04 weeks Time frame: Day-0 and 04 weeks Evaluation of neurological side effects by Modified Simpson Angus Scale Target Sample Size Total Sample Size=500 Sample Size from =500 page 6 / 9

7 Phase of Trial Phase 4 Date of First Enrollment () Date of First Enrollment (Global) Estimated Duration of Trial Recruitment Status of Trial (Global) Recruitment Status of Trial () Publication Details Brief Summary 07/04/2016 No Date Specified Years=2 Months=6 Days=0 Not Applicable Completed Not Yet This study is a open label, multi-centre trial to evaluate the safety and efficacy of FDC of Esomeprazole 40 mg + Levosulpiride SR 75 mg capsule once daily for 01 months in 500 patients with Short term therapy of Gastroesophageal reflux disease (GERD) in patients who do not respond to PPI alone that will be conducted in 08 centers in. The primary outcome measures will be Proportion of participants with adverse events and serious adverse events [Time frame: Baseline, Day-14, Day-28] The secondary outcomes will be Change in Frequency Scale for the Symptoms of GERD Scale (FSSG) from baseline [Time frame: 02 and 04 weeks] Change in Severity of symptoms of GERD by Likert Scale from baseline [Time frame: 02 and 04 weeks] Clinical Global Impression of Improvement (CGI-I) [Time frame: 02 and 04 weeks] Clinical Global Impression of Severity (CGI-S) [Time frame: Day-0 and 04 weeks] Evaluation of neurological side effects by Modified Simpson Angus Scale [Time frame: Day-0 and 04 weeks] Results and Conclusion: Our study showed that, mean change in Frequency scale for the symptoms of GERD (FSSG) scale, and mean change in Severity of symptoms of GERD by Likert Scale were statistically significant (P < ) at each visit (day 14 and 28). At the end of the study, fixed dose combination of Esomeprazole and Levosulpiride demonstrated good clinical response which was assessed by change in CGI-I at visit 3 (day 14) and visit 4 (day 28) and change in CGI-S at visit 4 (day 28). The efficacy results were similar in both ITT and PP population. Fixed dose combination of Esomeprazole and Levosulpiride was well tolerated. There was one patient who reported clinically significant degree of movement disorder as assessed by Modified Simpson Angus Scale after administration of fixed dose combination of Esomeprazole and Levosulpiride which was improved and patient was normal in all routine activities after 30 days of post treatment. page 7 / 9

8 Efficacy: We have observed that the mean change in total score of frequency scale for the symptoms of GERD Scale from baseline to day 28 was 10.98, the mean change in acid reflux score of frequency scale for the symptoms of GERD Scale from baseline to day 28 was 6.01, the mean change in dysmotility score of frequency scale for the symptoms of GERD Scale from baseline to day 28 was 5 and the mean change in severity of symptoms of GERD by Likert Scale from baseline to day 28 was The reduction in total score of frequency scale for the symptom of GERD scale from baseline to day 28 was statistically significant (P < ). The disease condition of 442 (91.6 %) patients improved from baseline by day 28 after administration of fixed dose combination of Esomeprazole and Levosulpiride. There were only 10 cases (2.1 %) of markedly ill after 28 days of treatment. There were no cases of the severely ill and most extremely ill patients by day 28 in this study. Overall, the Clinical Global Impression on Severity was reduced from baseline. Safety: A total of 61 adverse events occurred in 55 patients with an incidence of 11 % after administration of FDC of Esomeprazole and Levosulpiride. In terms of severity, distribution of these 61 AEs was mild (56), moderate (4) and severe (1). Relationship status of these AEs shows that a total of 21 AEs were considered as definite, 8 AEs were considered as probable, 1 AE was considered as possible, 5 AEs were considered as unlikely and 26 AEs were considered as unrelated to the study drug. Outcome of 60 out of 61 AEs were considered as recovered/ resolved. One patient reported EPS (extrapyramidal symptoms) as and AE on Visit 3 (14 days after treatment) and was withdrawn by investigator. It was mild in intensity and was recovered after 2 days. The adverse events with an incidence of greater than equal to 1 % were headache, pyrexia, blood prolactin increased and nasopharyngitis. The adverse events with an incidence of < 1 % were abdominal pain, nausea, cough, oropharyngeal pain, asthenia, pain, hepatic enzyme increased, platelet count decreased, extrapyramidal disorder. This is in line with adverse events reported from clinical studies and as well as post marketing experience of Esomeprazole and Levosulpiride. One death was reported in the study. Death was reported after discontinuation of the patient from the study. Death was reported as not related with study drug. FDC of Esomeprazole and Levosulpiride induced movement disorder (LIM) We have carried out evaluation of movement disorder (neurological) side effects by Modified Simpson Angus Scale. As per this scale, 470 patients (97.3 %) were normal, 12 patients (2.5 %) were having minimal degree of movement disorder and only one patient (0.2 %) was having clinically significant degree of movement disorder at end of visits. We believe the page 8 / 9

9 Powered by TCPDF ( reason for this finding was short term treatment duration (28 days). Our finding is in line with a study conducted by Shin HW et al., (2009). The authors of this study reported that interval between taking Levosulpiride and onset of Levosulpiride induced movement disorder was 4.5 months to 17.1 months. Hence, we believe there is no movement disorder safety concern with short term use of FDC. FDC of Esomeprazole and Levosulpiride and blood prolactin: Total 186 patients (37.2 %) among 500 patients were female. As per protocol, serum prolactin level was evaluated in females. We have observed that total 27 patients (5.4%) patients have reported raise in serum prolactin level after administration of FDC of Esomeprazole and Levosulpiride at visit 4 (day 28) in this study. None of these patients presented with any clinical manifestations related to hyperprolactinemia other than raised prolactin levels. None of the patients discontinued the study due to raised prolactin levels. Conclusion: Based on study results, it is concluded that Sompraz L (Esomeprazole 40 mg and Sustained Release Levosulpiride 75 mg) is safe and effective in short term therapy of Gastroesophageal Reflux Disease patients who do not respond to PPI alone. page 9 / 9