Back to resultsA 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 (BiGARD)
Primary Purpose
NSAID-induced Gastropathy
Status
Terminated
Phase
Phase 4
Locations
Russian Federation
Study Type
Interventional
Intervention
bismuth tripotassium dicitrate
pantoprazole
Sponsored by
About this trial
This is an interventional treatment trial for NSAID-induced Gastropathy focused on measuring De-Nol, NSAID-induced gastropathy, Pantoprazole, Bismuth tripotassium dicitrate, Russia
Eligibility Criteria
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.
Sites / Locations
- Site RU70001
- Site RU70008
- Site RU70012
- Site RU70006
- Site RU70013
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
bismuth tripotassium dicitrate and pantoprazole
pantoprazole
Arm Description
Participants will receive bismuth tripotassium dicitrate (twice daily) and pantoprazole (once daily) as single tablets
Participants will receive pantoprazole (once daily) as single tablet
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Number of participants with Physical Exam abnormalities and/or adverse events related to treatment
Number of participants with potentially clinically significant physical exam values
Number of participants with vital signs abnormalities and/or adverse events related to treatment
Number of participants with potentially clinically significant vital sign values
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
Number of participants with laboratory value abnormalities and/or adverse events related to treatment
Number of participants with potentially clinically significant laboratory values
Full Information
NCT ID
NCT02788123
First Posted
May 27, 2016
Last Updated
September 19, 2017
Sponsor
Astellas Pharma Europe B.V.
1. Study Identification
Unique Protocol Identification Number
NCT02788123
Brief Title
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
Acronym
BiGARD
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Terminated
Why Stopped
Internal reassessment of the medicinal product development strategy by Sponsor
Study Start Date
March 3, 2017 (Actual)
Primary Completion Date
May 29, 2017 (Actual)
Study Completion Date
June 13, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Europe B.V.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NSAID-induced Gastropathy
Keywords
De-Nol, NSAID-induced gastropathy, Pantoprazole, Bismuth tripotassium dicitrate, Russia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
bismuth tripotassium dicitrate and pantoprazole
Arm Type
Experimental
Arm Description
Participants will receive bismuth tripotassium dicitrate (twice daily) and pantoprazole (once daily) as single tablets
Arm Title
pantoprazole
Arm Type
Active Comparator
Arm Description
Participants will receive pantoprazole (once daily) as single tablet
Intervention Type
Drug
Intervention Name(s)
bismuth tripotassium dicitrate
Other Intervention Name(s)
De-Nol
Intervention Description
oral
Intervention Type
Drug
Intervention Name(s)
pantoprazole
Other Intervention Name(s)
Controloc
Intervention Description
oral
Primary Outcome Measure Information:
Title
Proportion of subjects in each group reaching complete healing of NSAID-induced gastropathy at week 2 of therapy
Description
Modified Lanza score 0-2 (inclusively) shall be considered as healing. The modified Lanza scale is utilized to grade the degree of gastritis
Time Frame
Week 2
Secondary Outcome Measure Information:
Title
Proportion of subjects reaching complete healing of NSAID-induced gastropathy in H.pylori-negative subjects in each treatment group at week 2
Description
Modified Lanza scale 0-2 scores (inclusively) shall be considered as complete healing
Time Frame
Week 2
Title
Proportion of subjects reaching complete healing of NSAID-induced gastropathy in H.pylori-positive subjects in each treatment group at week 2
Description
Modified Lanza scale 0-2 scores (inclusively) shall be considered as complete healing
Time Frame
Week 2
Title
Proportion of subjects reaching complete healing of NSAID-induced gastropathy in H.pylori-negative subjects in each treatment group at week 4
Description
Subjects reached complete healing of NSAID-induced gastric ulcers and erosions by Visit 2 shall also be analyzed
Time Frame
Week 4
Title
Proportion of subjects reaching complete healing of NSAID-induced gastropathy in H.pylori-positive subjects in each treatment group at week 4
Description
Subjects reached complete healing of NSAID-induced gastric ulcers and erosions by Visit 2 shall also be analyzed
Time Frame
Week 4
Title
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
Description
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
Time Frame
Week 2
Title
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
Description
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
Time Frame
Week 2
Title
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
Description
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
Time Frame
Week 4
Title
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
Description
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
Time Frame
Week 4
Title
Proportion of subjects reaching complete healing of NSAID-induced gastropathy in each treatment group at week 4
Description
Subjects reached complete healing of NSAID-induced gastric ulcers and erosions by Visit 2 shall also be analyzed
Time Frame
Week 4
Title
Changes in modified Lanza as compared to visit 1 (baseline) in H.pylori-negative subjects in each treatment group
Description
The modified Lanza scale is utilized to grade the degree of gastritis
Time Frame
Baseline, week 2 and week 4
Title
Changes in modified Lanza as compared to visit 1 (baseline) in H.pylori-positive subjects in each treatment group
Description
The modified Lanza scale is utilized to grade the degree of gastritis
Time Frame
Baseline, week 2 and week 4
Title
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
Description
The modified Lanza scale is utilized to grade the degree of gastritis
Time Frame
Baseline, week 2 and week 4
Title
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
Description
The modified Lanza scale is utilized to grade the degree of gastritis
Time Frame
Baseline, week 2 and week 4
Title
Changes in modified Lanza as compared to visit 1 (baseline) in each treatment group
Description
The modified Lanza scale is utilized to grade the degree of gastritis
Time Frame
Baseline, week 2 and week 4
Title
Changes in GSRS as compared to visit 1 (baseline) in H.pylori-negative subjects in each treatment group
Description
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
Time Frame
Baseline, week 2 and week 4
Title
Changes in GSRS as compared to visit 1 (baseline) in H.pylori-positive subjects in each treatment group
Description
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
Time Frame
Baseline, week 2 and week 4
Title
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
Description
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
Time Frame
Baseline, week 2 and week 4
Title
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
Description
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
Time Frame
Baseline, week 2 and week 4
Title
Changes in GSRS as compared to visit 1 (baseline) in each treatment group
Description
The GSRS contains a list of questions on subject's well-being within the period from subject's last visit to study site
Time Frame
Baseline, week 2 and week 4
Title
Safety assessed by nature, frequency and severity of Adverse Events (AEs)
Description
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
Time Frame
Up to day 35
Title
Safety assessed by nature, frequency and severity of Serious Adverse Events (SAEs)
Description
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
Time Frame
Up to day 35
Title
Number of participants with Physical Exam abnormalities and/or adverse events related to treatment
Description
Number of participants with potentially clinically significant physical exam values
Time Frame
Up to day 35
Title
Number of participants with vital signs abnormalities and/or adverse events related to treatment
Description
Number of participants with potentially clinically significant vital sign values
Time Frame
Up to day 35
Title
Safety assessed through esophagogastroduodenoscopy
Description
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
Time Frame
Up to day 35
Title
Number of participants with laboratory value abnormalities and/or adverse events related to treatment
Description
Number of participants with potentially clinically significant laboratory values
Time Frame
Up to day 35
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Astellas Pharma Russian affiliate
Official's Role
Study Director
Facility Information:
Facility Name
Site RU70001
City
Moscow
Country
Russian Federation
Facility Name
Site RU70008
City
Saint-Petersburg
Country
Russian Federation
Facility Name
Site RU70012
City
Saint-Petersburg
Country
Russian Federation
Facility Name
Site RU70006
City
Volgograd
Country
Russian Federation
Facility Name
Site RU70013
City
Volgograd
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
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
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