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Efficacy and Safety of DLBS2411 in the Management of GERD

Primary Purpose

Gastroesophageal Reflux Disease (GERD)

Status

Terminated

Phase

Phase 3

Locations

Indonesia

Study Type

Interventional

Intervention

Omeprazole

DLBS2411

Placebo capsule of Omeprazole

Placebo caplet of DLBS2411

About this trial

This is an interventional treatment trial for Gastroesophageal Reflux Disease (GERD) focused on measuring GERD, DLBS2411, omeprazole

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Agree to participate in the study under signed informed consent.
Male or female subjects aged 18-65 years old.
Subjects with diagnosis of GERD confirmed by endoscopy, with esophagitis grade A-B according to the LA Classification.
Able to take oral medication.
Subjects or subjects' legally acceptable representatives are able and willing to record adverse events in diary.
Subjects or subjects' legally acceptable representatives have the ability to comply with the trial protocol, including instruction for taking trial medication.

Exclusion Criteria:

For females of childbearing potential: pregnancy and breast-feeding.
- Patients must accept pregnancy tests during the trial if menstrual cycle is missed
- Fertile patients must use a reliable and effective contraceptive
Subjects with Zollinger Ellison syndrome or peptic ulcer diseases.
History or current evidence of Barrett's esophagus, esophageal strictures, odynophagia, pyloric stenosis, esophageal motility disorders (such as achalasia, scleroderma), anatomic esophageal abnormality (such as large hiatal hernia), pill-induced esophagitis.
Helicobacter pylori positive as confirmed by urea breath test (UBT).
History of esophageal, gastric or intestinal surgery including vagotomy.
Presence of comorbid diseases, such as symptomatic coronary artery disease (CAD) or cardiovascular disease, pulmonary disease (including asthma), hemostasis disorder, pancreatitis, malabsorption, or inflammatory bowel disease, and any other chronic diseases (including chronic cough, laryngitis), any serious infection(s), or malignancy(ies).
Inadequate liver function defined as ALT or alkaline phosphatase > 2.5 times upper limit of normal.
Inadequate renal function defined as estimated Glomerular Filtration Rate (eGFR) < 60 mL/min.
Taking any proton pump inhibitors (PPIs) or sucralfate within 14 days prior to screening.
Requiring regular and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, aspirin, anticholinergics, cholinergics, spasmolytics, or opiates, misoprostol or prokinetics.
Hypersensitivity to proton pump inhibitors.
Subjects with chronic alcoholism (>40 g alcohol/day) or drug abuse.
Active heavy smokers (i.e. consuming >10 cigarettes per day).
Participation in any other clinical studies within 30 days prior to screening.

Sites / Locations

Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Padjajaran Dr. Hasan Sadikin Hospital
Division of Gastroenterology Department of Internal Medicine Faculty of Medicine, University of Indonesia Dr. Cipto Mangunkusumo National General Hospital
Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Diponegoro Dr. Kariadi Hospital
Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Airlangga Dr. Soetomo Hospital
Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Gadjah Mada Dr. Sardjito Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Treatment 1

Treatment II

Arm Description

1 Omeprazole capsule 20 mg and 1 placebo caplet of DLBS2411, twice daily

1 DLBS2411 caplet 250 mg and 1 placebo capsule of Omeprazole, twice daily

Outcomes

Primary Outcome Measures

Healing rate by endoscopy

Healing rate is defined as proportion of subjects with either complete or achieving lower endoscopic grade of esophagitis (according to the Los Angeles (LA) classification) at Week 8 (end of study).

Secondary Outcome Measures

Changes in GERD Questionnaire (GERDQ) sum scores

Changes in GERDQ sum scores from baseline to Week 4 and Week 8 of treatment.

Composite heartburn and regurgitation response rate

Composite heartburn and regurgitation response rate: defined as proportion of subjects with neither heartburn nor acid regurgitation during the last 7 days (complete resolution of heartburn and acid regurgitation) by Week 4 and Week 8.

Heartburn response rate

Heartburn response rate: defined as proportion of subjects with no heartburn during the last 7 days (complete resolution of heartburn) by Week 4 and Week 8 (end of study).

Regurgitation response rate

Regurgitation response rate: defined as proportion of subjects with no regurgitation during the last 7 days (complete resolution of regurgitation) by Week 4 and Week 8 (end of study).

Overall response rate

Overall response rate: defined as proportion of subjects with controlled GERD symptoms by Week 4 and 8 of treatment, defined as proportion categorized as: complete relief (no GERD symptoms during the last 7-day); partial relief (a decrease in frequency but not complete relief of GERD symptoms during the last 7-day); and no response (increase or no change in frequency of GERD symptoms).

Vital sign

Vital sign (blood pressure) from baseline to every follow-up visit including end of study

Electrocardiography (ECG)

Electrocardiography (ECG) at baseline and at the end of study

Liver function

Liver function (serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin)from baseline to every follow-up visit including end of study

Renal function

Renal function (serum creatinine and blood urea nitrogen (BUN) level) from baseline to every follow-up visit including end of study

Adverse event

Adverse event, will be observed throughout the study conduct

Full Information

NCT ID

NCT03367195

First Posted

November 27, 2017

Last Updated

January 6, 2021

Sponsor

Dexa Medica Group

1. Study Identification

Unique Protocol Identification Number

NCT03367195

Brief Title

Efficacy and Safety of DLBS2411 in the Management of GERD

Official Title

Efficacy and Safety of DLBS2411 Compared to Omeprazole in the Management of Gastroesophageal Reflux Disease (GERD)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Terminated

Why Stopped

Very low recruitment rate. The Study Site classifies as tertiary referral hospital. Therefore, GERD Patients being referred to the site are mostly those with comorbidities included in the exclusion criteria.

Study Start Date

August 16, 2018 (Actual)

Primary Completion Date

May 4, 2020 (Actual)

Study Completion Date

September 9, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Dexa Medica Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a 2-arm, prospective, double-blind double-dummy, randomized-controlled study comparing DLBS2411 at a dose of 250 mg twice daily with omeprazole at a dose of 20 mg twice daily, given before morning and evening meals, for an 8-week course of therapy. Subjects should avoid taking meals 2-3 hours before bedtime. The bioactive fraction of DLBS2411 has been proved at cellular and genetic levels to have an antiulcer effect through both suppressing the gastric acidity and enhancing gastric mucosal protection. The anti-secretory effect of DLBS2411 is exerted through the inhibition of H+/K+ ATPase 'pump' as well as down-regulation of the H+/K+ ATPase gene expression, thus suppressing gastric acid secretion; while its cytoprotective defense mechanism works through the promotion of cyclooxygenase-2 (COX-2) derived prostaglandin (PgE2) synthesis, thus promoting gastrointestinal submucosal blood-flow, stimulating secretion of gastric-epithelial mucous and bicarbonate; anti-oxidative activity; and endothelial-nitric oxide (NO) formation. Recent study of DLBS2411 which was conducted in healthy volunteers, demonstrated the effective role and safety of DLBS2411 in suppressing intragastric acidity. Having such mechanisms of action, DLBS2411 is hypothesized to benefit patients with gastric acid disorders such as in gastroesophageal reflux disease (GERD).

Detailed Description

There will be 2 groups of treatment; each group will consist of 129 subjects with the treatment regimens for 8 weeks: Treatment I : 1 capsule of Omeprazole 20 mg and 1 placebo caplet of DLBS2411, twice daily Treatment II : 1 caplet of DLBS2411 250 mg and 1 placebo capsule of omeprazole, twice daily Each study medication will be administered twice daily, 30 minutes before morning (the first) and evening (the last) meals. The eligible subjects will be randomly allocated to receive study medication (Treatment 1 or Treatment 2) for 8 weeks of treatment, in a double blind fashion. They will be asked to come to the clinic every 4-week interval throughout the study period. Treatment Group 1 will receive Omeprazole twice daily and Placebo DLBS2411 twice daily. While Treatment Group 2 will receive DLBS2411 twice daily and Placebo Omeprazole twice daily. Subjects will be evaluated for treatment efficacy at baseline and at interval of 4 weeks over the 8-week course of therapy. Throughout the 8-week therapy, subjects should record the frequency (presence and absence) of each of GERD symptoms (heartburn, regurgitation, epigastric pain, nausea) daily in the provided Patient's Diary. The severity of each symptom experienced should also be self-evaluated and recorded. The safety profile of study medication other than vital signs and adverse event will be measured at baseline and end of study. Along the study, subjects should avoid taking meals 2-3 hours before bedtime. All subjects will be under direct supervision of a medical doctor during the study period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastroesophageal Reflux Disease (GERD)

Keywords

GERD, DLBS2411, omeprazole

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment 1

Arm Type

Active Comparator

Arm Description

1 Omeprazole capsule 20 mg and 1 placebo caplet of DLBS2411, twice daily

Arm Title

Treatment II

Arm Type

Experimental

Arm Description

1 DLBS2411 caplet 250 mg and 1 placebo capsule of Omeprazole, twice daily

Intervention Type

Drug

Intervention Name(s)

Omeprazole

Intervention Description

1 Omeprazole 20 mg capsules twice daily

Intervention Type

Drug

Intervention Name(s)

DLBS2411

Other Intervention Name(s)

Redacid

Intervention Description

1 DLBS2411 caplet 250 mg, twice daily

Intervention Type

Drug

Intervention Name(s)

Placebo capsule of Omeprazole

Intervention Description

1 placebo capsule of omeprazole, twice daily

Intervention Type

Drug

Intervention Name(s)

Placebo caplet of DLBS2411

Other Intervention Name(s)

Placebo caplet of Redacid

Intervention Description

1 placebo caplet of DLBS2411, twice daily

Primary Outcome Measure Information:

Title

Healing rate by endoscopy

Description

Healing rate is defined as proportion of subjects with either complete or achieving lower endoscopic grade of esophagitis (according to the Los Angeles (LA) classification) at Week 8 (end of study).

Time Frame

8 weeks

Secondary Outcome Measure Information:

Title

Changes in GERD Questionnaire (GERDQ) sum scores

Description

Changes in GERDQ sum scores from baseline to Week 4 and Week 8 of treatment.

Time Frame

4 and 8 weeks

Title

Composite heartburn and regurgitation response rate

Description

Time Frame

4 and 8 weeks

Title

Heartburn response rate

Description

Heartburn response rate: defined as proportion of subjects with no heartburn during the last 7 days (complete resolution of heartburn) by Week 4 and Week 8 (end of study).

Time Frame

4 and 8 weeks

Title

Regurgitation response rate

Description

Regurgitation response rate: defined as proportion of subjects with no regurgitation during the last 7 days (complete resolution of regurgitation) by Week 4 and Week 8 (end of study).

Time Frame

4 and 8 weeks

Title

Overall response rate

Description

Time Frame

4 and 8 weeks

Title

Vital sign

Description

Vital sign (blood pressure) from baseline to every follow-up visit including end of study

Time Frame

4 and 8 weeks

Title

Electrocardiography (ECG)

Description

Electrocardiography (ECG) at baseline and at the end of study

Time Frame

8 weeks

Title

Liver function

Description

Liver function (serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin)from baseline to every follow-up visit including end of study

Time Frame

4 and 8 weeks

Title

Renal function

Description

Renal function (serum creatinine and blood urea nitrogen (BUN) level) from baseline to every follow-up visit including end of study

Time Frame

4 and 8 weeks

Title

Adverse event

Description

Adverse event, will be observed throughout the study conduct

Time Frame

4 and 8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Agree to participate in the study under signed informed consent. Male or female subjects aged 18-65 years old. Subjects with diagnosis of GERD confirmed by endoscopy, with esophagitis grade A-B according to the LA Classification. Able to take oral medication. Subjects or subjects' legally acceptable representatives are able and willing to record adverse events in diary. Subjects or subjects' legally acceptable representatives have the ability to comply with the trial protocol, including instruction for taking trial medication. Exclusion Criteria: For females of childbearing potential: pregnancy and breast-feeding. Patients must accept pregnancy tests during the trial if menstrual cycle is missed Fertile patients must use a reliable and effective contraceptive Subjects with Zollinger Ellison syndrome or peptic ulcer diseases. History or current evidence of Barrett's esophagus, esophageal strictures, odynophagia, pyloric stenosis, esophageal motility disorders (such as achalasia, scleroderma), anatomic esophageal abnormality (such as large hiatal hernia), pill-induced esophagitis. Helicobacter pylori positive as confirmed by urea breath test (UBT). History of esophageal, gastric or intestinal surgery including vagotomy. Presence of comorbid diseases, such as symptomatic coronary artery disease (CAD) or cardiovascular disease, pulmonary disease (including asthma), hemostasis disorder, pancreatitis, malabsorption, or inflammatory bowel disease, and any other chronic diseases (including chronic cough, laryngitis), any serious infection(s), or malignancy(ies). Inadequate liver function defined as ALT or alkaline phosphatase > 2.5 times upper limit of normal. Inadequate renal function defined as estimated Glomerular Filtration Rate (eGFR) < 60 mL/min. Taking any proton pump inhibitors (PPIs) or sucralfate within 14 days prior to screening. Requiring regular and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, aspirin, anticholinergics, cholinergics, spasmolytics, or opiates, misoprostol or prokinetics. Hypersensitivity to proton pump inhibitors. Subjects with chronic alcoholism (>40 g alcohol/day) or drug abuse. Active heavy smokers (i.e. consuming >10 cigarettes per day). Participation in any other clinical studies within 30 days prior to screening.

Overall Study Officials: