A double-blind, placebo controlled, randomized, two centre phase IIa pharmacodynamic cross-over study to assess the effect of AZD3355, 65 mg bid, on transient lower esophageal sphincter relaxations (TLESRs) in GERD patients with incomplete response to PPI - n.a.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 30

Inclusion Criteria

1. Provision of informed consent
2. Male or female (females must be postmenopausal (ie, >12 months without a menstrual period and >50 years of age) or be bilaterally oophorectomized or hysterectomized)
3. Age 18-70 years
4. Weight 60-100 kg
5. At least 6 months history of GERD symptoms (need not to be consecutive) and a history of an incomplete response to PPI treatment
6. Continuously treated with an approved dose of any PPI during at least 6 weeks before enrolment
7. Ability to read and write and to use the e-diary
8. Screening questionnaire (RDQ) indicating a burning feeling behind the breastbone with a frequency of at least 3 days over the past 7 days and with at least mild intensity and/or unpleasant movement of material upwards from the stomach with a frequency of at least 3 days over the past 7 days and with at least mild intensity

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Screening questionnaire (RDQ) indicating an equal or higher intensity of pain in the centre of the upper stomach than for a burning feeling behind the breastbone, if not fulfilling the inclusion criteria regarding unpleasant movement of material upwards from the stomach
2. History of clinically significant cardiovascular, respiratory, renal, hepatic, neurological, mental or gastrointestinal (excluding GERD) disease. Patients with uncomplicated and well controlled Diabetes Mellitus and patients with uncomplicated and well controlled hypertension (SBP =160 mmHg and DBP =90 mmHg) can be included
3. S-creatinine >1.2 times upper limit of normal (based on laboratory results from pre-entry visit)
4. History of clinically significant orthostatic reactions
5. Systolic blood pressure below 110 mmHg
6. History of heart disease (eg, ischemic heart disease, congestive heart failure, cardiac arrhythmias) or signs or symptoms of heart disease including QTc >480 ms or other ECG abnormalities
7. Prior surgery of the upper GI tract (open, endoscopic and laparoscopic surgery on the esophagus, the stomach and the duodenum with the exception of over-sewing or endoscopic treatment of a bleeding ulcer).
8. History of severe allergy/hypersensitivity or symptoms/signs of ongoing allergy/hypersensivity
9. Need for concomitant medication with:
Drugs that may interfere with the pharmacodynamic effect of Investigational Product (eg, baclofen). Drugs that may influence gastrointestinal symptoms, (eg, H2 receptor antagonists, sucralphate, alginates, tegaserod, metoclopamid, drugs with significant anticholinergic effect, non-steroid anti-inflammatory drugs (NSAIDs), cyclo-oxygenase-2 (COX-2) inhibitors, acetylsalicylic acid (ASA) >160 mg, biphosphonates, antineoplastic drugs) with exception of the PPI and used in the study and antacids
Drugs that have a narrow therapeutic window (eg warfarin, digoxin, phenytoin, karbamazepin). Drugs that may prolong the QT interval (see CPSP supplement C for common examples)
10. History of drug addiction, alcohol abuse or other circumstances which in the investigators judgement may compromise the patient’s ability to comply with the study requirements
11. Any other condition which in the opinion of the investigator would render the patient unsuitable for inclusion in the study
12. Blood donation within 4 weeks prior to administration of the first dose of the investigational product
13. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)
14. Administration of any investigational product or participation in any clinical study within 8 weeks prior to administration of the first dose of the investigational product
15. Previous participation in a study with this compound or previous enrolment or randomization of treatment in the present study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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