CTRI/2023/11/059403 [Registered on: 01/11/2023] Trial Registered Prospectively
Last Modified On:
13/05/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A Clinical Trial to Assess the effect of Tegoprazan in patients with Erosive Gastroesophageal Reflux Disease
Scientific Title of Study
Multi-National, Multi-Centric, Prospective, Randomized, Double-Blind, Active-controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Tegoprazan in Patients with Erosive Gastroesophageal Reflux Disease
DRL-IND-NDA08-TEG/2022 Version No. 4.0 dated 26-JUN-2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Jayashri Krishnan
Designation
Vice President Operations
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
Tower 2, 1st Floor, South Wing,
L&T Business Park,
Plot no 12/4, Sector 27 D,
Delhi Mathura Road, Near Sarai Khwaja Metro Station, Faridabad -121003, Haryana, India
Faridabad HARYANA 121003 India
Phone
919771407484
Fax
44-22249884
Email
jayashri.krishnan@jssresearch.com
Details of Contact Person Scientific Query
Name
Dr Jayashri Krishnan
Designation
Vice President Operations
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
Tower 2, 1st Floor, South Wing,
L&T Business Park,
Plot no 12/4, Sector 27 D,
Delhi Mathura Road, Near Sarai Khwaja Metro Station, Faridabad -121003, Haryana, India
HARYANA 121003 India
Phone
919771407484
Fax
44-22249884
Email
jayashri.krishnan@jssresearch.com
Details of Contact Person Public Query
Name
Dr Ramprasath TR
Designation
Associate Director Operations
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
Tower 2, 1st Floor, South Wing,
L&T Business Park,
Plot no 12/4, Sector 27 D,
Near Sarai Khwaja Metro Station, Delhi Mathura Road, Faridabad -121003, Haryana, India
Fatehabad HARYANA 121003 India
Phone
919444101300
Fax
44-22249884
Email
ramprasath@jssresearch.com
Source of Monetary or Material Support
Dr. Reddy’s Laboratories Ltd.
Integrated Product Development,
Innovation plaza, Survey No: 42, 45 and 46,
Bachupally village, Bachupally Mandal
Medchal Malkajgiri District 500 090, Telangana, India
Primary Sponsor
Name
Dr. Reddy’s Laboratories Ltd.
Address
Integrated Product Development,
Innovation plaza, Survey No: 42, 45 and 46,
Bachupally village, Bachupally Mandal Medchal Malkajgiri District 500 090, Telangana, India.
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
Dr Reddys Laboratories Ltd
Integrated Product Development,
Innovation plaza, Survey No: 42, 45 and 46,
Bachupally village, Bachupally Mandal Medchal Malkajgiri District 500 090, Telangana, India.
Research Department,
Ground Floor,
S. No. 32/2A, Erandwane,
Pune – 411004, Maharashtra India
Pune MAHARASHTRA
9021133704
drnachi@yahoo.co.in
Dr Himanshu Patel
Aman Hospital and Research Center
Room No. – Consultation Room
Floor No. – Ground Floor
Department- Research Department
Site Address : 15, Shashwat, Opp ESI Hospital, Gotri Road Vadodara-390021
Vadodara GUJARAT
8141001672
dr.himanshuvpatel@gmail.com
Dr Rakesh Patel
Ashirwad Hospital and Research Centre
Room No. – NA
Floor No. – 3rd floor
Department - Department of research
Address -
Ashirwad Hospital and Research Centre,Maratha Section, Near Jijamata Udhyan,Ulhasnagar-421004
Thane MAHARASHTRA
9834613273
rppatelg@yahoo.com
Dr Rupa Banerjee
Asian Institute of Gastroenterology
Room No. – 02, Ibd center,
Floor No. – 06
Department – Gastroenterology
AIG Hospitals,
1-66/AIG/2 to 5, Mindspace Rd,
P Janardhan Reddy Nagar, Gachibowli,
Hyderabad, Telangana 500032
Hyderabad TELANGANA
9849287530
drrupabanerjee.aig@gmail.com
Dr Anumala Kavitha
Governement general hospital
Department of Gastroenterology
Room No:220, Department of Gastroenterology,
Government General Hospital, Guntur Andhra Pradesh India.
Guntur ANDHRA PRADESH
9399977555
jananigastro@gmail.com
Dr Ajay Kumar Patwa
King Georges Medical University
Room No. – NA
Floor No. – 1st Floor
Department - Department of Medicine,
King George’s Medical university,
Shahmeena Road, Chowk, Lucknow-226003.
Lucknow UTTAR PRADESH
Room No. – 15
Floor No. – 1st Floor
Department-Department of Gastroenterology
East building, Marengo CIMS Hospital Pvt Ltd, Off. Science city road, Sola, Ahmedabad-380060
Ahmadabad GUJARAT
9727707214
bhavesh.thakkar@marengoasia.com
Dr Nemade Pankaj Ramesh
Medipoint Hospitals Pvt. Ltd.
Room No. – NA
Floor No. – 3
Department- Research
Site Address- Medipoint Hospitals Pvt. Ltd.,
241/1, New D. P. Road, Aundh, Pune-411007, Maharashtra, India.
Pune MAHARASHTRA
8087521353
drpankajnemade.medipoint@gmail.com
Dr Chetan Nalin Mehta
Shree Giriraj Multispecialty Hospital
Room No. – NA
Ground Floor
Department – General OPD Department
Address - 27-Navjyot Park Corner,150 feet ring road, Rajkot-360005
Rajkot GUJARAT
9825077472
mehtacn@hotmail.com
Dr Mahesh Mangulkar
Supe Heart & Diabetes Hospital and Research Center
Room No. – 05
Floor No. – 1st floor
Department - OPD 02
Address - Supe Heart and Diabetes Hospital and Research Center,
opp. Adhar Ashram near Runghta High School,
Gharpure Ghat Ashok Stambh, Nashik,
Maharashtra, 422002. INDIA.
Nashik MAHARASHTRA
8087537224
drmaheshmangulkar22@gmail.com
Dr Kabrawala Mayank Vasantlal
Surat Institute 0f Digestive Sciences (SIDS) Hospital & Research Centre
Room No. – NA
1st Floor
Department – Gastroenterology
Address - Surat Institute of Digestive Sciences, Vijay Nagar Gate No-3, Besides Nirman Bhavan, Opposite Gandhi College, Majura Gate, Ring Road, Surat- 395002, Gujarat, India
Surat GUJARAT
9825130363
mayankkabrawala@hotmail.com
Dr Venugopal Hunasanahalli
Victoria Hospital, BMC&RI
Room No. – NA
Floor No. – Ground Floor,
Department - Dept. Of Surgical Gastroenterology Address -
Ground Floor, Dept. Of Surgical Gastroenterology, Victoria Hospital,Fort, K.R. Road, Bangalore- 560002
Bangalore KARNATAKA
9845527042
drvenugopalhg@gmail.com
Dr B Ravishankar
Yashoda Hospitals
Room No. – 09
Floor No. – 4th floor
Department – Department of Gastroenterology
Yashoda Hospitals,
Behind Hari Hara Kala Bhavan,
SP Road,
Secunderabad - 500003,
Telangana, India
Hyderabad TELANGANA
IEC, Research Cell, Administrative block, - King George’s Medical university Chowk, Lucknow-226003
Submittted/Under Review
ACE HOSPITAL- ACE Hospital and Research Centre 32/2 A, Erandawane, Gulwani Maharaj Road Pune
Approved
Ashirwad Ethics Committee Ashirwad Hospital and Research Centre Maratha Section, Near Jijamata Udyan Ulhasnagar Thane Maharashtra - 421004 India
Approved
Bangalore Medical College and Research Institute
Approved
Care Institute of Medical Sciences Care Institute of Medical Sciences Nr. Shukan Mall, Off Science City Road, Sola Ahmedabad Gujarat - 380060 India
Approved
ETHICS COMMITTEE GMC and GGH Guntur Medical College Kannavari Thota Main Road Guntur Guntur Andhra Pradesh - 522004 India
Approved
Institutional Ethics Committee Aman Hospital and Research Center
Approved
Institutional Ethics Committee Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad,500082, India
Approved
Malla Reddy Narayana Multispeciality Hospital, Suraram X roads, Jeedimetla, Hyderabad-500055
Approved
Penta-Med Ethics Committee
Approved
Shree Giriraj Hospital 27-Navjyot Park Corner, 150 feet ring road, Rajkot-360005, Gujarat, India
Approved
Supe Hospital Ethics Committee Supe Heart Diabetes Hospital And Research Centre
Approved
Surat Institute of digestive sciences ethics committee
Approved
Yashoda Academy of Medical Education and Research Yashoda Hospitals Behind Hari Hara kala Bhawan SP Road Secunderabad, Hyderabad Telangana - 500003 India
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: K210||Gastro-esophageal reflux disease with esophagitis,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Esomeprazole 40 mg tablet
Esomeprazole 40 mg one tablet, orally and T-Placebo one tablet, orally, once daily for up to 8 weeks
Intervention
Tegoprazan 50 mg tablet
Tegoprazan 50 mg one tablet, orally and R-placebo one tablet, orally, once daily for up to 8 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Subjects must be able to understand the requirements of the study and be willing to give written informed consent
2. Males and females aged 18-65 years (both inclusive)
3. Subjects Diagnosed with LA Grade A-D erosive esophagitis on an upper gastrointestinal endoscopy within 14 days prior to randomization.
Los Angeles (LA) Classification System for erosive esophagitis:
Grade Findings
A One or more mucosal break, no longer than 5 mm, that does not extend between the tops of 2 mucosal folds
B One or more mucosal break, more than 5 mm long, that does not extend between the tops of two mucosal folds
C One or more mucosal break, that is continuous between the tops of two or more mucosal folds, but which involve less than 75% of the circumference
D One or more mucosal breaks involving 75% or more of the esophageal circumference.
4. Subjects who have experienced both heartburn (burning feeling behind breastbone, pain behind breastbone) and regurgitation for at least 2 days if symptoms are mild or for at least 1 day for moderate to severe symptoms within 7 days prior to visit 1
severity will be defined as mentioned below
Point scales for symptom assessment
0 None No symptom
1 Mild There is symptom but no interference with routine activity including sleep
2 Moderate Slight discomfort and interference with routine activity including sleep
3 Severe Symptoms exist for most of the times and interfere with routine activity including sleep
frequently.
4 Very Severe Symptoms exist consistently and interfere with routine activity including sleep
substantially.
5. Females of childbearing potential must have a negative serum pregnancy test at the Screening
6. Consent to use medically appropriate method of birth control or complete abstinence from sexual contacts throughout the study
• medically appropriate method of birth control included intrauterine devices, physical barrier (cervical caps with spermicide, diaphragms with spermicide, condoms with spermicides), sustained release injections of birth control, oral contraceptives, tubal ligation, and vasectomy; it is recommended to use dual contraceptive methods in order not to become pregnant during the study.
• women under medically sterile condition are allowed to participate in this study as follows; post menopause (amenorrhea for longer than 24 months), hysterectomy, tubectomy and bilateral oophorectomy.
ExclusionCriteria
Details
Patients will not be entered into the study only if they meet any of the following criteria.
1.Subjects who are unable to undergo upper GI endoscopy.
2.Presence of oesophageal stricture, ulcer stricture, gastroesophageal varices, Barretts oesophagus, active gastric ulcer, gastrointestinal bleeding, or malignant tumour confirmed on an upper GI endoscopy
3.Subjects having symptoms suggestive of malignant gastrointestinal disorder such as
odynophagia, severe dysphagia, bleeding, weight loss, anemia, or bloody stool.
4.Subjects diagnosed with eosinophilic esophagitis
5.Diagnosed with primary esophageal motility disorder, irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) within recent 3 months or suspected of IBS.
A patient who was suspected of IBS based on physical examination including abdominal discomfort, stool consistency, and frequency by the investigator will be excluded
6.History of gastric acid suppression surgery, oesophageal or gastric surgery except for simple fenestration, appendectomy, cholecystectomy, or endoscopic excision of benign tumour
7. Subjects who have taken PPIs within 2 weeks prior to upper GI endoscopy
8. Having taken two or more commercial doses of reflux esophagitis related medications (including H2 blockers, prostaglandins, mucosal protective agents) within 1 week prior to upper GI endoscopy
9.Requirement of persistent daily use of drugs during the study or treatment within one week of randomization that may cause an ulcer such as nonsteroidal anti-inflammatory drugs (NSAIDs) except for low dose aspirin (≤100 mg/day) taking prior to study participation for prophylactic use
persistent use is defined as requirement of chronic use (>12 doses per month) of non-steroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 (COX-2) NSAIDs within 30 days prior to the Screening Period and throughout the study.
10. Participants who are receiving prohibited medications and are unable to discontinue these drugs for the study duration
11. Pregnant or lactating women
12. Abnormal laboratory results with clinical relevance at screening as follow
AST ≥ 2x upper limit of normal (ULN)
ALT ≥ 2x ULN
ALP ≥ 2x ULN
γ-GT≥ 2x ULN
Total bilirubin ≥ 2x ULN
BUN ≥ 1.5x ULN
Creatinine ≥ 1.5x ULN
13. Abnormal ECG of clinical significance including major arrhythmia, multifocal PVC, second degree AV block
14. History or Presence of Zollinger-Ellison syndrome.
15. History of malignancy or any ongoing malignancy at the time of screening
16.Clinically significant hepatic, renal, cardiovascular, respiratory, endocrine or central nervous system (CNS) disorder
17. History of hypersensitivity to the active ingredient or excipients of the study drug including esomeprazole
18. Participation in the other clinical trial within 4 weeks prior to randomization or received any investigational agent prior to randomization within 5 half-lives of the investigational agent as per Investigator discretion.
19.The subject has a history of alcohol abuse, illegal drug use, or drug addiction within the 12 months prior to screening, or regularly consumes >21 units of alcohol (1 unit 12 oz/300 mL beer, 1.5 oz/25 mL hard liquor/spirits, or 5 oz/100 mL wine) per week based on self-report.
20. Any clinically significant condition or situation other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.
21. Subjects positive for H. Pylori at screening
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
Evaluation of efficacy of Tegoprazan 50 mg tablet as compared to Esomeprazole 40 mg tablet in patients with erosive gastroesophageal reflux disease.
1. Mean Cumulative endoscopic healing rate of erosive esophagitis by 8 week based on
the upper GI endoscopy.
2. Subjects who will be having the complete endoscopic healing following 4 weeks of treatment
completion of the study and the result at week 4 will be used as the primary endpoint.
14 days, 28, & 56 days
Secondary Outcome
Outcome
TimePoints
Evaluation of safety & tolerability of Tegoprazan 50 mg tablet as compared to Esomeprazole 40 mg tablet in patients with erosive gastroesophageal reflux dis-ease.
Healing rate of erosive esophagitis at 4 week based on the upper GI endoscopy following
2. weeks of study treatment.
3. Mean change in GERD-HRQL (GERD-Health related quality life) score from baseline
4. to week 2, 4 & 8.
5. Symptom assessment based on subject diary at 1, 2, 4 & 8 weeks
14 days, 28, & 56 days
Target Sample Size
Total Sample Size="254" Sample Size from India="178" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Gastroesophageal
reflux disease (GERD) is a disease characterized by typical heartburn or
several symptoms caused by the reflux of gastric acid or food into the
esophagus.
Non-erosive reflux
disease (NERD) is characterized by the presence of the typical symptoms of GERD
without visible erosive esophagitis on endoscopy and erosive esophagitis (EE)
is characterized by injury to the esophageal mucosa on endoscopy.
The global pooled
prevalence of GERD is 13.98% and varies greatly according to region from a range
of 12.88% -22.40%.
The prevalence of
GERD in India ranges from 7.6% to 30%, in Russia is 13.3%. According to a study
conducted in Nigeria, a typical African population, the overall prevalence of
GERD was estimated to be 7.6%.
Tegoprazan is a
benzimidazole derivative potassium-competitive acid blockers (P-CABs) that was
developed by HK inno.N Corp in Korea; for treatment of GERD and peptic ulcer
The introduction of
the potassium-competitive acid blockers (P-CABs) has been a significant advance
in the pharmacological control of gastric acid secretion.
P-CABs offer a more
rapid elevation of intragastric pH than DR-PPIs, while maintaining the same
degree of antisecretory effect. Compared with PPIs, tegoprazan does not need
activation in an acidic environment; therefore, tegoprazan exhibits a faster
onset than PPIs and has highly selective and reversible inhibitory properties
against H+/K+-ATPase in parietal cells.
Compared to
conventional PPIs, tegoprazan has a longer half-life and reversible binding
properties, thus exhibiting a higher inhibition rate for nocturnal acid
breakthrough.
Tegoprazan has the advantage of being less affected by CYP2C19-mediated
drug interactions than PPIs such as omeprazole, esomeprazole, and lansoprazole