Research of Efficient Use of Omeprazole in Combination With Domperidone in Gastroesophageal Reflux Disease of Mild to Moderate Severity

Research of Efficient Use of Omeprazole in Combination With Domperidone in Gastroesophageal Reflux Disease of Mild to Moderate Severity

The purpose of this study is to determine the efficacy, safety, and tolerability of omeprazole in combination with domperidone in GERD treatment for subsequent efficient pharmacotherapy of GERD.

Objectives of the trial To assess the efficacy of omeprazole in combination with domperidone regarding change of incidence and severity of clinical symptoms of GERD during 8 weeks of treatment To compare the efficacy of omeprazole in combination with domperidone regarding change of incidence and severity of clinical symptoms of GERD during 8 weeks of treatment To assess the efficacy of omeprazole in combination with domperidone regarding change of incidence and severity of endoscopic symptoms of GERD during 8 weeks of treatment To compare the efficacy of omeprazole in combination with domperidone regarding change of incidence and severity of endoscopic symptoms of GERD during 8 weeks of treatment To determine the efficiency and advantages of one GERD therapy considering efficacy, safety, and individual variance of patients' reactions

Study design . Primary and secondary endpoints

Primary endpoint:

• reduced incidence and severity of heartburn after 8 weeks of treatment with Omez-DSR preparation in comparison with OMEZ preparation.

Secondary endpoints:

• reduced severity of heartburn estimated against visual analog scale after 8 weeks of treatment;
• incidence of events of heartburn after 4 and 8 weeks of treatment;
• proportion of patients with completely jugulated heartburn at the 4th and 8th weeks of treatment;
• number of days without heartburn after 4 weeks of treatment;
• proportion of patients with resolved esophagitis after 8 weeks of treatment in subjects with esophagitis at the time of enrollment.

Safety endpoints:

• incidence of adverse events in the group of patients who received at least one dose of the medicinal product after randomization;
• incidence of serious adverse events;
• incidence of severe adverse events;
• incidence of adverse events definitely caused by administration of the tested medicinal product.

Description of the trial planned By its design the trial will be a randomized open comparative parallel study.

Study flow chart:

Screening=>Randomization=>Group 1(Omez-DSR),Group 2(Omez) =>Treatment=>Monitoring

13.3. Phases of the trial:

1. Screening - preliminary selection of subjects according to clinical criteria; signing of informed consent; prescription and conduction of screening procedures; decision on inclusion/exclusion of subject from the trial on the grounds of the results of screening procedures according to inclusion/exclusion criteria.
2. Randomization - random distribution of subjects included into the trial into two groups: group 1 - treatment with tested Omez-DSR preparation, group 2 - treatment with the comparator Omez.
3. Treatment - patients receive either Omez-DSR preparation or Omez preparation in the prescribed regimen according to the randomization number. Treatment shall be ambulatory; patients shall visit research center through specified periods.
4. After the end of treatment patients shall return to their usual lifestyle, but they are monitored to assess the efficacy of the therapy conducted and to record adverse events.

Description of measures allowing reducing the bias factor Randomization Randomization at phase 2 shall be performed using the WinPepi statistical program, option Masking Partial masking shall be used. Assessment of endoscopic examination at week 8 of treatment shall be blinded; the specialist conducting endoscopy shall not know which therapy was used. Statistical analysis shall be performed after coding of subjects; and during analysis it shall not be known which of the groups is receiving Omez-DSR, and which one - Omez.

Description of treatment Medical preparations authorized in the Republic of Belarus shall be used in the trial: Omez-DSR and Omez.

Dosage Dosage shall be performed in accordance with label recommendations of Omez-DSR and Omez preparations. Dose of Omez shall be 2 capsules/day (40 mg of omeprazole). Dose of Omez-DSR shall be 2 capsules/day (40 mg of omeprazole and 60 mg of domperidone).

Regimen Medicinal preparations shall be prescribed after randomization. Group 1 or OM-DP: the subjects from this group shall be supplied the preparation enough for 8 weeks of treatment. Group 2 or OM: the subjects shall be supplied the preparation enough for 8 weeks.

Features of the phases of the trial

Signing of informed consent:Screening, Assessment of inclusion/exclusion criteria:Screening,Randomization Complaints Screening,Randomization,Week 8/End of treatment,Monitoring After 28 days

Past and present history: Screening,Randomization Drug history: Screening,Week 8/End of treatment, Monitoring After 28 days Physical examination: Screening,Randomization,Week 8/End of treatment, Monitoring After 28 days Height, weight measurement: Screening,Week 8/End of treatment, Monitoring After 28 days Survey against the GERD-Q scale (values of 7 scores): Screening,Week 8/End of treatment Distribution of diaries:Randomization Esophagogastroduodenoscopy: Screening,Week 8/End of treatment Pregnancy test: Screening Distribution of preparation:Randomization Recording of adverse events:Week 8/End of treatment, Monitoring After 28 days Compliance assessment:Week 8/End of treatment

Criteria of inclusion of subjects

• desire to participate in the trial and ability to sign the informed consent;
• age above 18;
• gastroesophageal reflux disease, manifested in heartburn no less than twice a week prior to the 1st visit;
• use for the trial period of safe contraception methods for women of fertile age;
• results of ultrasonography (US) of abdominal cavity organs (ACO) performed in the last 6 months before the enrollment.

Criteria of non-inclusion refusal to undergo the endoscopic examination;

• gastroesophageal reflux disease with severe esophagitis (grade С or D against the Los Angeles classification);
• Barrett esophagus;
• pregnancy or lactation;
• administration of nonsteroidal antiinflammatory drugs (NSAIDs), aspirin, bisphosphonates, nitrates, calcium antagonists, proton pump inhibitors or Н2-blockers, prokinetics, clopidogrel;
• participation in other clinical trial;
• history of allergic reaction or intolerance of components of medicinal products;
• esophageal stricture;
• gastrectomy or gastric resection;
• malignant neoplasms in any location at present;
• alcohol abuse;
• severe cardiovascular or respiratory insufficiency;
• hepatic insufficiency;
• renal insufficiency.

Criteria of exclusion

• investigator's opinion on the necessity to exclude the patient for their own benefit;
• erroneous enrollment;
• investigator's decision to exclude the patient due to serious deviation from the trial program;
• serious adverse events (SAEs) including death (stating the date of death);
• adverse events (AEs) requiring monitoring and drug therapy;
• acute diseases or conditions which in the investigator's opinion require the patient to be excluded from the trial;
• administration during the trial of NSAIDs, aspirin, bisphosphonates, nitrates, calcium antagonists, proton pump inhibitors or Н2-blockers, prokinetics, antacids (except for the tested MP or the comparator MP) or the necessity for such treatment to be prescribed;
• positive pregnancy test (for women);
• patient's failure to appear for the visit;
• patient's refusal to continue the trial;
• intolerance of the tested MP or the comparator MP;