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 (BiGARD)

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

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.

Study Overview

• Status: Terminated
• Conditions: NSAID-induced Gastropathy
• Intervention / Treatment: Drug: bismuth tripotassium dicitrate; Drug: pantoprazole

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Site RU70001
  • Saint-Petersburg, Russian Federation
    • Site RU70008
  • Saint-Petersburg, Russian Federation
    • Site RU70012
  • Volgograd, Russian Federation
    • Site RU70006
  • Volgograd, Russian Federation
    • Site RU70013

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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: De-Nol; Drug: pantoprazole; oral; Other Names: Controloc
Active Comparator: pantoprazole; Participants will receive pantoprazole (once daily) as single tablet	Drug: pantoprazole; oral; Other Names: Controloc

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.
• Investigators: Study Director: Medical Monitor, Astellas Pharma Russian affiliate

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2017
• Primary Completion (Actual): May 29, 2017
• Study Completion (Actual): June 13, 2017

Study Registration Dates

• First Submitted: May 27, 2016
• First Submitted That Met QC Criteria: May 27, 2016
• First Posted (Estimate): June 2, 2016

Study Record Updates

• Last Update Posted (Actual): September 21, 2017
• Last Update Submitted That Met QC Criteria: September 19, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Russia; Pantoprazole; De-Nol; NSAID-induced gastropathy; Bismuth tripotassium dicitrate
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antacids; Bismuth; Pantoprazole; Bismuth tripotassium dicitrate
• Other Study ID Numbers: 3593-MA-3026-RU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No