A phase IIa, double-blind, randomized, 2-way cross-over study to evaluate the effect of a single dose of AZD1386 95 mg compared to placebo in a multimodal experimental pain model on esophageal sensitivity in GERD patients with a partial response to PPI treatment - na
- Conditions
- Gastroesophageal Reflux Disease (GERD) is the intended indicationMedDRA version: 9.1Level: LLTClassification code 10017924Term: Gastroesophageal reflux
- Registration Number
- EUCTR2008-007420-26-SE
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
1. Provision of signed informed consent before any study specific procedures
2. Able to read and write
3. Able and willing to comply with all study requirements
4. Have reported in the modified RDQ-RI screening instrument (7-day recall) a burning feeling behind the breastbone with a frequency of at least 3 days or more over the past 7 days and with at least moderate intensity and/or unpleasant movement of material upwards from the stomach with a frequency of at least 3 days or more over the past 7 days and with at least moderate intensity.
5. Male or female, age 18-70 years, inclusive. Females must not be of childbearing potential or must have used one of the following highly effective contraceptive methods for the last 3 months, in addition, they must have two negative pregnancy tests at V1 and V3 with at least 14 days between the visits.
No childbearing potential criteria
- Post-menopausal females (either of);
- Females >50 years and have been amenorrheic for 12 months or more and have not used exogenous hormonal treatment
- Females >50 years and have been amenorrheic for 12 months or more, following cessation of all exogenous hormonal treatments
- Females >57 years regardless of whether they are on Hormonal Replacement Therapy (HRT)
- Permanent sterilisation by hysterectomy and/or bilateral oophorectomy
Women of childbearing potential must use one of the following highly effective contraceptive methods
- True abstinence (ie, not just stopping intercourse for the duration of the trial).
- Vasectomised sexual partner (with appropriate post-vasectomy documentation of the absence of sperm in ejaculate.
- Implanon® (Etonogestrel slow-release subcutaneous implant)
- Female sterilisation by bilateral tubal ligation/occlusion
- IUD/IUS provided coils are copper-banded
- Mirena® - levonorgestrel containing IUS
- Depo Provera® injections (medroxyprogesterone)
- Normal and low dose combined oral contraceptive (COC)—only if used in TriCycle regime. This means instead of taking a single 3-week course of COC pills followed by one week off COC, the patient takes 3 or 4 courses together (i.e., 9-12 weeks of daily COC) with, between each prolonged cycle, a shortened 4-day pill free interval (PFI) rather than the usual 7-day PFI. Note: the less commonly used Triphasic pills, which have different strength pills in the same pack, are not considered highly effective and are therefore excluded from this instruction.
- Evra Patch: norelgestromin/ethinyl estradiol transdermal system—only if used in above. Tricycle regime with 4-day patch-free intervals after each long cycle
- Nuvaring (intravaginal device containing ethinyloestradiol and etonogestrel (3-ketodesogestrel)—only if used in above Tricycle regime with 4-day ring-free intervals after each long cycle
- Cerazette™ (desogestrel-releasing progestogen-only pill with established failure rate of <1 per 100 women in first year).
6. BMI 18.5 – 35.0, inclusive
7. Have at least 6 months history of GERD symptoms (need not to be consecutive) and one of the following:
(a) A gastroscopy, not demonstrating an erosive condition or any other serious abnormality, as judged by the investigator, within the last 2 years and with no significant deterioration in symptoms since gastroscopy.
(b) A gastroscopy performed as a screening procedure, if no gastroscopy has been done within the last 2 years, not demonstrating an erosive condition or any other serious abnormality, as judged by the investigator.
8. Continuously
1. Patients that have not experienced any GERD symptoms improvement at all after PPI treatment (non-responders)
2. PPI treatment with doses outside the approved label for GERD and GERD related indications. Note: Twice daily (bid) dosing is not allowed.
3. Unstable or clinically significant disorders including cardiovascular, respiratory, renal, hepatic, metabolic, psychiatric, other gastrointestinal and esophageal disorders besides GERD. Patients with uncomplicated, well-controlled hypertension (SBP £140 and DBP £90) could be included.
- Clinical significant is defined as disorders that could compromise patients’ safety or interfere with the evaluation of the study as judged by the investigator.
4. Concomitant use of strong and moderate CYP3A4 enzyme inhibitors, such as ketoconazole, itraconazole, clarithromycin, nefazodone, erythromycin, fluconazole, aprepitant, diltiazem, verapamil, grapefruit juice, HIV protease inhibitors.
5. History of malignancy, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin.
6. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This includes subjects with any of the following:
- Clinically significant PR (PQ) interval prolongation
- Intermittent second or third degree AV block
- Incomplete, full or intermittent bundle branch block (QRS < 110ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy)
- Abnormal T wave morphology, particularly in the protocol defined primary lead
- Prolonged QTcF >450 msec or shortened QTcF <350 msec
- Family history of long QT syndrome
7. ASAT or ALAT > 2 times ULN or bilirubin 1.5 times ULN at pre-entry visit
8. Clinically significant abnormalities in clinical chemistry, haematology or urinalysis results as judged by the investigator
9. Prior surgery of the upper GI tract (open, endoscopic and laparoscopic surgery on the esophagus, the stomach and the duodenum with the exception of oversewing or endoscopic treatment of bleeding ulcer)
10. History of severe allergy/hypersensitivity or symptoms/signs of ongoing allergy/hypersensitivity
11. Need for concomitant medication with the following:
Drugs that may interfere with the pharmacodynamic effect of the Investigational Product
Drugs that may influence gastrointestinal symptoms.
12. Risk factors for ventricular fibrillation eg family history of short QT syndrome (SQTS) or sudden cardiac death (SCD) among first-degree relatives
13. History of drug addiction, drug abuse (including cannabinoids) or alcohol abuse and/or positive drug screen or other circumstances which in the investigators judgment may compromise the patient’s ability to comply with the study requirements
15. Excessive intake of caffeine containing drinks eg, coffee, tea, caffeine containing energy drinks or Coke (more than 5 cups of coffee or equivalent per day)
16. Pregnant or breast feeding females
17. Any other condition which in the opinion of the investigator would render the patient unsuitable for inclusion in the study
18. Plasma or blood donation within two weeks prior to enrollment or any blood loss equivalent to the amount of a blood donation during the 3 months prior to enrollment
19. Involvement in the planning or conduct of the study (applies to both AZ staff and staff at the study site)
20. Administration of any investigational product within 8 weeks
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