A Study To Assess The Efficacy And Safety Of Bismuth Tripotassium Dicitrate (De-Nol) In Combination With Pantoprazole And Pantoprazole Monotherapy In Treatment Of Subjects With Nonsteroidal Anti-Inflammatory Drugs (NSAID)-Induced Gastropathy

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate clinical efficacy of bismuth tripotassium dicitrate (De-Nol) in combination with pantoprazole versus pantoprazole monotherapy in subjects with NSAID-induced gastropathy in 14±2 days of treatment.

Detailed Description
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This study has a screening period (up to 3±2 days duration). Randomization will be held in each stratum (H. pylori-positive and H. pylori-negative) on the Visit 1. Treatment period will consist of 2 visits: Visit 2 (up to 14±2 days after Visit 1) in subjects with completely healed ulcer(s) and erosions after control esophagogastroduodenoscopy (EGDS) and Visit 3 (up to 28±2 days after Visit 1) in subjects with not healed ulcers and erosions after control EGDS on Visit 2. The period of follow-up safety assessments will last 1 week after the end of the study treatment

Official Title
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Phase IV, Multicenter, Open Label, Randomized Study in Parallel Groups To Assess The Efficacy And Safety Of Bismuth Tripotassium Dicitrate (De-Nol®) In Combination With Pantoprazole And Pantoprazole Monotherapy In Treatment Of Patients With NSAID Induced Gastropathy

Conditions
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NSAID-induced Gastropathy

Intervention / Treatment
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* Drug: bismuth tripotassium dicitrate
* Drug: pantoprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Verified diagnosis of NSAID-induced gastropathy: Presence of gastric ulcer(s) and/or erosions (modified Lanza score greater than or equal to 5) based on EGDS findings at screening and; NSAIDs administration within 7 days before screening. Negative pregnancy test at screening and at Visit 1 (for females only using test strip to detect chorionic gonadotropin in urine), Subjects' consent to use a reliable contraception method starting from screening throughout the whole study and for 1 week after its termination. Exclusion Criteria: Severe complications of NSAID-gastropathy (bleedings, perforations, etc.) The subjects requiring concomitant therapy using the drugs specified in Forbidden concomitant therapy. Ulcerative esophagitis grade C and higher according to Los-Angeles classification. Expressed hepatic and renal impairment. Any esophageal and gastric surgery that can make subject ineligible for study participation. Abuse of psychoactive substances including alcohol which may interfere with the subject's participation and fulfillment of all the protocol requirements. Participation in other clinical studies within 30 days prior to Screening Visit. Administration of bismuth products less than 2 months prior to screening. Administration of PPIs or histamine Н2-receptor antagonists less than 2 weeks prior to screening. Hypersensitivity to any of the components of the study drugs or contraindications to them. Pregnancy and lactation. Inability to perform follow-up EGDS after 2 and/or 4 weeks of the study. Any condition or concomitant disease and laboratory parameter abnormalities which renders the subject ineligible for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bismuth tripotassium dicitrate and pantoprazole<br>Participants will receive bismuth tripotassium dicitrate (twice daily) and pantoprazole (once daily) as single tablets | Drug: bismuth tripotassium dicitrate<br>* oral<br>* Other names: De-Nol;Drug: pantoprazole<br>* oral<br>* Other names: Controloc;|
| Active Comparator: pantoprazole<br>Participants will receive pantoprazole (once daily) as single tablet | Drug: pantoprazole<br>* oral<br>* Other names: Controloc;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects in each group reaching complete healing of NSAID-induced gastropathy at week 2 of therapy | Modified Lanza score 0-2 (inclusively) shall be considered as healing. The modified Lanza scale is utilized to grade the degree of gastritis | Week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects reaching complete healing of NSAID-induced gastropathy in H.pylori-negative subjects in each treatment group at week 2 | Modified Lanza scale 0-2 scores (inclusively) shall be considered as complete healing | Week 2 | 
| Proportion of subjects reaching complete healing of NSAID-induced gastropathy in H.pylori-positive subjects in each treatment group at week 2 | Modified Lanza scale 0-2 scores (inclusively) shall be considered as complete healing | Week 2 | 
| Proportion of subjects reaching complete healing of NSAID-induced gastropathy in H.pylori-negative subjects in each treatment group at week 4 | Subjects reached complete healing of NSAID-induced gastric ulcers and erosions by Visit 2 shall also be analyzed | Week 4 | 
| Proportion of subjects reaching complete healing of NSAID-induced gastropathy in H.pylori-positive subjects in each treatment group at week 4 | Subjects reached complete healing of NSAID-induced gastric ulcers and erosions by Visit 2 shall also be analyzed | Week 4 | 
| Proportion of subjects reaching complete healing of NSAID-induced gastropathy in subjects with NSAID-induced gastropathy with modified Lanza scale greater than or equal to 5 and <7 at screening in each treatment group at week 2 | The modified Lanza scale is utilized to grade the degree of gastritis. Modified Lanza scale 0-2 scores (inclusively) shall be considered as complete healing | Week 2 | 
| Proportion of subjects reaching complete healing of NSAID-induced gastropathy in subjects with NSAID-induced gastropathy with modified Lanza scale =7 at screening in each treatment group at week 2 | The modified Lanza scale is utilized to grade the degree of gastritis. Modified Lanza scale 0-2 scores (inclusively) shall be considered as complete healing | Week 2 | 
| Proportion of subjects reaching complete healing of NSAID-induced gastropathy in subjects with NSAID-induced gastropathy with modified Lanza scale greater than or equal to 5 and <7 at screening in each treatment group at week 4 | The modified Lanza scale is utilized to grade the degree of gastritis. Modified Lanza scale 0-2 scores (inclusively) shall be considered as complete healing. Subjects reached complete healing of NSAID-induced gastric ulcers and erosions by Visit 2 shall also be analyzed | Week 4 | 
| Proportion of subjects reaching complete healing of NSAID-induced gastropathy in subjects with NSAID-induced gastropathy with modified Lanza scale =7 at screening in each treatment group at week 4 | The modified Lanza scale is utilized to grade the degree of gastritis. Modified Lanza scale 0-2 scores (inclusively) shall be considered as complete healing. Subjects reached complete healing of NSAID-induced gastric ulcers and erosions by Visit 2 shall also be analyzed | Week 4 | 
| Proportion of subjects reaching complete healing of NSAID-induced gastropathy in each treatment group at week 4 | Subjects reached complete healing of NSAID-induced gastric ulcers and erosions by Visit 2 shall also be analyzed | Week 4 | 
| Changes in modified Lanza as compared to visit 1 (baseline) in H.pylori-negative subjects in each treatment group | The modified Lanza scale is utilized to grade the degree of gastritis | Baseline, week 2 and week 4 | 
| Changes in modified Lanza as compared to visit 1 (baseline) in H.pylori-positive subjects in each treatment group | The modified Lanza scale is utilized to grade the degree of gastritis | Baseline, week 2 and week 4 | 
| Changes in modified Lanza as compared to Visit 1 (baseline) in subjects with NSAID-induced gastropathy with modified Lanza scale greater than or equal to 5 and <7 at screening in each treatment group | The modified Lanza scale is utilized to grade the degree of gastritis | Baseline, week 2 and week 4 | 
| Changes in modified Lanza as compared to Visit 1 (baseline) in subjects with NSAID-induced gastropathy with modified Lanza scale =7 at screening in each treatment group | The modified Lanza scale is utilized to grade the degree of gastritis | Baseline, week 2 and week 4 | 
| Changes in modified Lanza as compared to visit 1 (baseline) in each treatment group | The modified Lanza scale is utilized to grade the degree of gastritis | Baseline, week 2 and week 4 | 
| Changes in GSRS as compared to visit 1 (baseline) in H.pylori-negative subjects in each treatment group | Gastrointestinal Symptom Rating Scale (GSRS). The GSRS contains a list of questions on subject's well-being within the period from subject's last visit to study site | Baseline, week 2 and week 4 | 
| Changes in GSRS as compared to visit 1 (baseline) in H.pylori-positive subjects in each treatment group | Gastrointestinal Symptom Rating Scale (GSRS). The GSRS contains a list of questions on subject's well-being within the period from subject's last visit to study site | Baseline, week 2 and week 4 | 
| Changes in GSRS as compared to Visit 1 (baseline) in subjects with NSAID-induced gastropathy with modified Lanza scale greater than or equal to 5 and <7 at screening in each treatment group | The GSRS contains a list of questions on subject's well-being within the period from subject's last visit to study site. The modified Lanza scale is utilized to grade the degree of gastritis | Baseline, week 2 and week 4 | 
| Changes in GSRS as compared to Visit 1 (baseline) in subjects with NSAID-induced gastropathy with modified Lanza scale =7 at screening in each treatment group | The GSRS contains a list of questions on subject's well-being within the period from subject's last visit to study site. The modified Lanza scale is utilized to grade the degree of gastritis | Baseline, week 2 and week 4 | 
| Changes in GSRS as compared to visit 1 (baseline) in each treatment group | The GSRS contains a list of questions on subject's well-being within the period from subject's last visit to study site | Baseline, week 2 and week 4 | 
| Safety assessed by nature, frequency and severity of Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a subject administered a study drug or has undergone study procedures and which does not necessarily have a causal relationship with this treatment | Up to day 35 | 
| Safety assessed by nature, frequency and severity of Serious Adverse Events (SAEs) | Adverse event (AE) is considered serious if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important events | Up to day 35 | 
| Number of participants with Physical Exam abnormalities and/or adverse events related to treatment | Number of participants with potentially clinically significant physical exam values | Up to day 35 | 
| Number of participants with vital signs abnormalities and/or adverse events related to treatment | Number of participants with potentially clinically significant vital sign values | Up to day 35 | 
| Safety assessed through esophagogastroduodenoscopy | Amount of gastric content and its nature (mucus, bile, blood), gastric mucosa condition (edema, hyperemia, erosions, mucosal hemorrages, atrophy, hypertrophy) shall be evaluated during esophagogastroduodenoscopy | Up to day 35 | 
| Number of participants with laboratory value abnormalities and/or adverse events related to treatment | Number of participants with potentially clinically significant laboratory values | Up to day 35 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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De-Nol, NSAID-induced gastropathy, Pantoprazole, Bismuth tripotassium dicitrate, Russia