ong-term safety of Z-338 in Patients with Functional Dyspepsia (Condition that causes an upset stomach or pain or discomfort in the upper abdomen).
- Conditions
- Functional DyspepsiaMedDRA version: 18.0Level: LLTClassification code 10064536Term: Functional dyspepsiaSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2013-003342-16-BG
- Lead Sponsor
- Zeria Pharmaceutical Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 500
Inclusion criteria for run-in period:
Subjects will be eligible to enter the run-in period if all of the following criteria are met:
1. Subjects to provide written informed consent prior to any study procedures being performed.
2. Male or female subjects aged 18 years or over, inclusive, on the day the informed consent is signed.
3. Subjects with a diagnosis of FD (postprandial distress syndrome) as defined by the Rome III Criteria* (see Appendix A). Criteria must be fulfilled for the 3 months prior to informed consent with symptom onset at least 6 months prior to informed consent.
Symptoms must include one or both of the following:
i. Bothersome postprandial fullness (PPF), occurring after ordinary-sized meals, more than 1 day per week
ii. Early satiation (ES) that prevents finishing a regular meal, more than 1 day per week
There must be no evidence of structural disease (including at upper endoscopy) that is likely to explain the symptoms.
4. Subjects must have consulted for dyspeptic symptoms at least once during the 6 months prior to informed consent. If there are no medical records, the subject should be asked when the symptoms started.
5. Subjects must present PPF or ES as the most bothersome symptom during the 6 months prior to informed consent.
6. Subjects must have a normal endoscopy result within the 6 months (3 months in case of subjects who are H. pylori positive) prior to informed consent or during the screening period.
• If no normal endoscopy results are available from the 6 months (3 months for H. pylori positive subjects) prior to informed consent, an endoscopy must be conducted during the screening period and must be normal for the subject to be eligible. If H. pylori status is unknown, then a H. pylori test must be conducted during the screening period although H. pylori status (i.e., positive or negative) is not an eligibility criterion.
7. Subjects must be able to understand the study, comply with the study requirements, and return to the investigational site for assessments at specified times.
8. Subjects must be able to understand the symptom definitions and how to record their severity using the LPDS incorporated in an electronic Patient Reported Outcome (ePRO) device.
9. Female subjects of childbearing potential must provide a negative pregnancy test (urine dipstick) at screening (Visit 1 or 2). Female subjects of childbearing potential must agree to use acceptable contraceptive methods (i.e., contraceptive implant, injectable or patch hormone therapy, oral contraceptives in combination with barrier methods [e.g., condoms] supplemented with spermicidal foam/gel/film/cream/suppository, intrauterine device, sexual abstinence, or surgical sterilisation of the subject or the subject’s sexual partner) during the screening, run-in, treatment, and follow-up periods. Non-childbearing potential includes being surgically sterilized at least 6 months prior to informed consent, post-menopausal, or defined as amenorrhoea for at least 12 months prior to informed consent.
Male subjects with partners of childbearing potential must agree to use acceptable contraceptive methods (i.e., barrier method [e.g., condoms] supplemented with spermicidal foam/gel/film/cream/suppository in combination with another contraceptive measure as described above) during the screening, run-in, treatment, and follow-up periods.
Inclusion criteria for open-label treatment period
Subjects will be eligible to enter the open-label trea
1.Subjects on PPI(s) who are unable to discontinue PPI medication by the end of the screening period (Visit 2).
•Subjects taking PPIs at the time of informed consent will be asked to discontinue the medication and return after a 14- to 21-day washout period to complete screening assessments at Visit 2.
2. Subjects taking drugs that affect gut motility, gut sensitivity and/or acid secretion (see list of prohibited medications, Appendix B) who are unable to discontinue these drugs by the end of the screening period(Visit 2).
•Subjects taking drugs that affect gut motility, gut sensitivity and/or acid secretion* at the time of informed consent will be asked to discontinue the medication and return after a 14- to 21-day washout period to complete screening assessments at Visit 2.*Note: no washout is required for medications listed in the antacids and cytoprotectors” category in Appendix B.
3.Subjects taking non-steroidal anti-inflammatory drugs (NSAIDs). However, aspirin administration not exceeding 500 mg per day for cardiovascular primary prophylaxis is allowed.
4.Subjects taking QT-time prolonging drugs, e.g., macrolide antibiotics and CYP3A4 inhibiting azole-type antimycotics.
5.Subjects who have received H. pylori eradication therapy during the 3 months prior to informed consent.
6.Subjects with confirmed organic gastrointestinal disease.
7.Subjects with a history of surgery that can affect gastrointestinal motility including endoscopic surgery for gastro-oesophageal reflux disease (GORD) and obesity.
•Subjects with former uncomplicated appendectomy, cholecystectomy, and/or laparoscopic surgery may be included.
8.Subjects presenting with predominant complaints relieved by stool movements(irritable bowel syndrome).
9.Subjects presenting with predominant GORD symptoms(e.g., heartburn, regurgitation, chest pain).
10.Subjects presenting with predominant complaints of chronic idiopathic nausea.
11.Subjects with Type I or Type II diabetes.
12.Subjects with active uncontrolled psychiatric and/or psychosomatic disorders, depression, alcohol, or substance abuse in the 2 years prior to informed consent.
•Subjects with a stable condition(as judged by the Investigator) taking one form of medication of standard dose antidepressant for at least 3 months prior to informed consent may be included. However, subjects taking Amitriptyline or Nortriptyline must be excluded even if prescribed as monotherapy.
•Subjects taking one anxiolytic alone, one sedative alone, or one hypnotic alone once a day at night for sleep problems may be included. However, subjects taking a combination of these drugs must be excluded.
13.Subjects with known hypersensitivity to gastroprokinetic drugs.
14.Subjects with cardiovascular problems, history of arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, and/or subjects with any kind of risk of QT prolongation.
•Subjects who suffer from controlled and non-complicated hypertension, as judged by the Investigator, may be included. However subjects taking clonidine, alphamethyldopa beta blockers, and/or organonitrates must be excluded.
15.Subjects with any evidence of, or treatment for, malignancy(with the exception of basal cell carcinoma) within the 5 years prior to informed consent.
16.Subjects with body mass index(BMI) over 30 kg/m2.
17.Subjects with a clinically significant renal, hepatic, cardiovascular, pulmonary, endocrine, metabolic, or haematological condition, as judged by th
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the long-term safety of 100 mg Z-338 three times a day (TID) in subjects with Functional Dyspepsia.;Secondary Objective: To explore:<br>• The use of the Leuven Postprandial Distress Scale (LPDS) to measure Functional Dyspepsia symptom severity, and the effect of Z-338.<br>• The effect of Z-338 on the Quality of Life (QoL) in subjects with Functional Dyspepsia as measured by the Short Form-36 (SF-36) survey and the Short Form-Nepean Dyspepsia Index (SF-NDI).<br>• The effect of Z-338 on work productivity in subjects with Functional Dyspepsia as measured by the Work Productivity and Activity Impairment (WPAI).;Primary end point(s): The long-term safety of Z-338 100 mg TID will be evaluated by assessment of:<br>• AEs<br>• ECGs<br>• Laboratory variables<br>• Vital signs<br>• Physical examination;Timepoint(s) of evaluation of this end point: 58 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The efficacy of Z-338 100 mg TID will be explored by assessment of the following Patient Reported Outcomes:<br>• Change of each individual symptom score of the subject measured by LPDS<br>• Global outcome of the subject measured by OTE<br>• Change of QoL score of the subject measured by the SF-36 survey and the SF-NDI<br>• Change of work productivity of the subject measured by WPAI;Timepoint(s) of evaluation of this end point: 52 weeks