Clinical trial NCT02818309: Lesogaberan in Chinese Patients With Refractory Reflux Symptoms
Official title: Efficacy and Safety of Lesogaberan (AZD3355) in Chinese Patients With Reflux Symptoms Refractory to Proton Pump Inhibitor Therapy: a Randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastroesophageal Reflux Disease
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Technology, Taiwan
First posted: 2016-06-29
Enrollment: 72
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lesogaberan may be used in Chinese GERD patients with partial response to PPI.

Detailed description: To test the efficacy and safety of lesogaberan.

Eligibility criteria: Inclusion criteria

1. Provision of informed consent prior to any study specific procedures.
2. Male or female. Females of childbearing potential must have been using a highly effective contraceptive method for at least the previous 3 months.
3. Age 20-70 years, inclusive.
4. Body Mass Index (BMI) 18.5 - 35.0 kg/m2, inclusive.
5. Have at least 6 months history of Gastroesophageal reflux disease (GERD) symptoms (need not to have been consecutive) and endoscopy documented erosive esophagitis within 4 months.
6. Continuously treated during the last 8 weeks before enrolment with daily optimised unchanged standard dose proton pump inhibitor (PPI) therapy, such as esomeprazole 40 mg, lansoprazole 30 mg, dexlansoprazole 60 mg, rabeprazole 30 mg and pantoprazole 40 mg.
7. Able to read and write in the local language and use the e-diary device.
8. To be eligible for the screening phase the patients must have reported in the Reflux Symptom Questionnaire 7 day recall (RESQ-7) using 7 days recall of symptoms, a minimum of 3 days with a rating of at least moderate intensity on at least 1 of the following items; a burning feeling behind the breastbone or unpleasant movement of material upwards from the stomach.
9. To be eligible for randomisation the patients must have recorded in the Reflux Symptom Questionnaire electronic diary (RESQ-eD) on the last 7 days before randomisation, a minimum of 3 days with a symptom intensity of at least moderate on 1 of 2 items (a burning feeling behind the breastbone or an unpleasant movement of material upwards from the stomach), or any combination of both items (eg, 1 day on 1 item and 2 days on the other).

Exclusion criteria

1. Patients that had not experienced any GERD symptom improvement at all during PPI treatment.
2. Unstable or clinically significant cardiovascular (ischemic heart disease, congestive heart failure, arrhythmia), respiratory (chronic obstructive pulmonary disease), hepatic (AST or ALT or total bilirubin \> upper limit of normal), renal (\>1.5 mg/dL), metabolic (serum potassium or magnesium \< lower reference range), psychiatric (major depression, schizophrenia) , or gastrointestinal and esophageal disorders besides GERD (peptic ulcer, eosinophilic esophagitis).
3. Current neurological disorders including nerve compression syndromes. Patients with well controlled migraine and other headache disorders could be included.
4. History of clinically significant orthostatic reaction or syncope.
5. History of a heart disease (including ischemic heart disease, congestive heart failure, cardiac arrhythmias, congenital long QT syndrome), or current signs or symptoms of any heart disease, or patients with clinically significant ECG abnormalities or QTcF \>450 ms as determined by the investigator.
6. History of, or current malignant disease (radically treated basal cell cancer was allowed).
7. History of clinically significant electrolyte imbalances.
8. History of severe allergic or hypersensitivity reactions (such as Stevens Johnson syndrome, anaphylactic shock, angioedema-urticaria).
9. Using concomitant drugs that could potentially interfere with the pharmacodynamic effects of lesogaberan (such as baclofen or supplements containing GABA), alter gastrointestinal symptoms (such as type-2 histamine receptor agonists) or cause damage to the mucosal lining of the gastrointestinal tract (such as nonsteroidal anti-inflammatory drugs or acetylsalicylic acid \>162 mg/day).
10. Prior surgery of the upper GI tract
11. Pregnant or breastfeeding females

Primary outcomes:
measure: Treatment response as assessed by the symptom questionnaire RESQ-eD
timeFrame: 3 years
Secondary outcomes:
measure: Time to treatment response as assessed by the symptom questionnaire RESQ-eD
timeFrame: 3 years
measure: Time to sustained absence of symptoms as assessed by the symptom questionnaire RESQ-eD
timeFrame: 3 years
measure: The proportion of symptom-free days as assessed by the symptom questionnaire RESQ-eD
timeFrame: 3 years
measure: The change from baseline for each separate symptom domain of the RESQ-eD
timeFrame: 3 years
measure: Patients' consumption of rescue antacid medication over the 4 week treatment period
timeFrame: 3 years
measure: Patient compliance with treatment determined by counts of returned unused capsules at each visit during the period of randomised treatment
timeFrame: 3 years
measure: Subgroup analysis of in patients with different reflux profiles categorized by impedance-pH as assessed by the symptom questionnaire RESQ-eD
timeFrame: 3 years
measure: Number of participants with treatment-related adverse events as assessed by CRF_20150728
timeFrame: 3 years
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Ping-Huei Tseng, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: