Lesogaberan in Chinese Patients With Refractory Reflux Symptoms

Efficacy and Safety of Lesogaberan (AZD3355) in Chinese Patients With Reflux Symptoms Refractory to Proton Pump Inhibitor Therapy: a Randomized Placebo-controlled Trial

Sponsors

Lead Sponsor: National Taiwan University Hospital

Collaborator: Ministry of Science and Technology, Taiwan

Source National Taiwan University Hospital
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.

Overall Status Unknown status
Start Date January 2015
Completion Date December 2017
Primary Completion Date November 2017
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Treatment response as assessed by the symptom questionnaire RESQ-eD 3 years
Secondary Outcome
Measure Time Frame
Time to treatment response as assessed by the symptom questionnaire RESQ-eD 3 years
Time to sustained absence of symptoms as assessed by the symptom questionnaire RESQ-eD 3 years
The proportion of symptom-free days as assessed by the symptom questionnaire RESQ-eD 3 years
The change from baseline for each separate symptom domain of the RESQ-eD 3 years
Patients' consumption of rescue antacid medication over the 4 week treatment period 3 years
Patient compliance with treatment determined by counts of returned unused capsules at each visit during the period of randomised treatment 3 years
Subgroup analysis of in patients with different reflux profiles categorized by impedance-pH as assessed by the symptom questionnaire RESQ-eD 3 years
Number of participants with treatment-related adverse events as assessed by CRF_20150728 3 years
Enrollment 72
Condition
Intervention

Intervention Type: Drug

Intervention Name: Lesogaberan

Description: 120 mg bid

Arm Group Label: Lesogaberan

Other Name: AZD3355

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo

Arm Group Label: Placebo

Other Name: Placebo for AZD3355

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

Gender: All

Minimum Age: 20 Years

Maximum Age: 70 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Ping-Huei Tseng, MD, PhD Principal Investigator National Taiwan University Hospital
Location
Facility: National Taiwan University Hospital
Location Countries

Taiwan

Verification Date

June 2016

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Lesogaberan

Type: Experimental

Description: Lesogaberan

Label: Placebo

Type: Placebo Comparator

Description: Placebo

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov