Clinical trial NCT03367195: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Gastroesophageal Reflux Disease (GERD)
Keywords: GERD
DLBS2411
omeprazole
Lead sponsor: Dexa Medica Group
Sponsor class: INDUSTRY
First posted: 2017-12-08
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. 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
2. Subjects with Zollinger Ellison syndrome or peptic ulcer diseases.
3. 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.
4. Helicobacter pylori positive as confirmed by urea breath test (UBT).
5. History of esophageal, gastric or intestinal surgery including vagotomy.
6. 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).
7. Inadequate liver function defined as ALT or alkaline phosphatase \> 2.5 times upper limit of normal.
8. Inadequate renal function defined as estimated Glomerular Filtration Rate (eGFR) \< 60 mL/min.
9. Taking any proton pump inhibitors (PPIs) or sucralfate within 14 days prior to screening.
10. Requiring regular and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, aspirin, anticholinergics, cholinergics, spasmolytics, or opiates, misoprostol or prokinetics.
11. Hypersensitivity to proton pump inhibitors.
12. Subjects with chronic alcoholism (\>40 g alcohol/day) or drug abuse.
13. Active heavy smokers (i.e. consuming \>10 cigarettes per day).
14. Participation in any other clinical studies within 30 days prior to screening.

Primary outcomes:
measure: Healing rate by endoscopy
timeFrame: 8 weeks
Secondary outcomes:
measure: Changes in GERD Questionnaire (GERDQ) sum scores
timeFrame: 4 and 8 weeks
measure: Composite heartburn and regurgitation response rate
timeFrame: 4 and 8 weeks
measure: Heartburn response rate
timeFrame: 4 and 8 weeks
measure: Regurgitation response rate
timeFrame: 4 and 8 weeks
measure: Overall response rate
timeFrame: 4 and 8 weeks
measure: Vital sign
timeFrame: 4 and 8 weeks
measure: Electrocardiography (ECG)
timeFrame: 8 weeks
measure: Liver function
timeFrame: 4 and 8 weeks
measure: Renal function
timeFrame: 4 and 8 weeks
measure: Adverse event
timeFrame: 4 and 8 weeks
Other outcomes:
Locations:
city: Bandung
country: Indonesia
facility: Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Padjajaran Dr. Hasan Sadikin Hospital
city: Jakarta
country: Indonesia
facility: Division of Gastroenterology Department of Internal Medicine Faculty of Medicine, University of Indonesia Dr. Cipto Mangunkusumo National General Hospital
city: Semarang
country: Indonesia
facility: Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Diponegoro Dr. Kariadi Hospital
city: Surabaya
country: Indonesia
facility: Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Airlangga Dr. Soetomo Hospital
city: Yogyakarta
country: Indonesia
facility: Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Gadjah Mada Dr. Sardjito Hospital
Study officials:
affiliation: Division of Gastroenterology Department of Internal Medicine Faculty of Medicine, University of Indonesia Dr. Cipto Mangunkusumo National General Hospital, Jakarta Indonesia
name: Dadang Makmun, SpPD, KGEH
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Airlangga Dr. Soetomo Hospital, Surabaya, Indonesia
name: Iswan A. Nusi, Prof. KGEH, FINASIM, FACG
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Gadjah Mada Dr. Sardjito Hospital, Yogyakarta, Indonesia
name: Putut Bayupurnama, SpPD, KGEH
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Diponegoro Dr. Kariadi Hospital, Semarang, Indonesia
name: Hery D. Purnomo, SpPD, KGEH
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Padjajaran Dr. Hasan Sadikin Hospital, Bandung, Indonesia
name: Dolvy Girawan, M. Kes., SpPD, KGEH
role: PRINCIPAL_INVESTIGATOR
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