BiGARD: 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 Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: bismuth tripotassium dicitrate and pantoprazole Participants will receive bismuth tripotassium dicitrate (twice daily) and pantoprazole (once daily) as single tablets |
Drug: bismuth tripotassium dicitrate
oral
Other Names:
Drug: pantoprazole
oral
Other Names:
|
| Active Comparator: pantoprazole Participants will receive pantoprazole (once daily) as single tablet |
Drug: pantoprazole
oral
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of subjects in each group reaching complete healing of NSAID-induced gastropathy at week 2 of therapy [Week 2]
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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [Baseline, week 2 and week 4]
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 [Baseline, week 2 and week 4]
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 [Baseline, week 2 and week 4]
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 [Baseline, week 2 and week 4]
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 [Baseline, week 2 and week 4]
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 [Baseline, week 2 and week 4]
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 [Baseline, week 2 and week 4]
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 [Baseline, week 2 and week 4]
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 [Baseline, week 2 and week 4]
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 [Baseline, week 2 and week 4]
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) [Up to day 35]
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) [Up to day 35]
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 [Up to day 35]
Number of participants with potentially clinically significant physical exam values
- Number of participants with vital signs abnormalities and/or adverse events related to treatment [Up to day 35]
Number of participants with potentially clinically significant vital sign values
- Safety assessed through esophagogastroduodenoscopy [Up to day 35]
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 [Up to day 35]
Number of participants with potentially clinically significant laboratory values
Eligibility Criteria
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.
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Abuse of psychoactive substances including alcohol which may interfere with the subject's participation and fulfillment of all the protocol requirements.
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Participation in other clinical studies within 30 days prior to Screening Visit.
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Administration of bismuth products less than 2 months prior to screening.
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Administration of PPIs or histamine Н2-receptor antagonists less than 2 weeks prior to screening.
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Hypersensitivity to any of the components of the study drugs or contraindications to them.
-
Pregnancy and lactation.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site RU70001 | Moscow | Russian Federation | ||
| 2 | Site RU70008 | Saint-Petersburg | Russian Federation | ||
| 3 | Site RU70012 | Saint-Petersburg | Russian Federation | ||
| 4 | Site RU70006 | Volgograd | Russian Federation | ||
| 5 | Site RU70013 | Volgograd | Russian Federation |
Sponsors and Collaborators
- Astellas Pharma Europe B.V.
Investigators
- Study Director: Medical Monitor, Astellas Pharma Russian affiliate
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 3593-MA-3026-RU