Effect of Netazepide on Omeprazole-induced Changes in Chromogranin A and Gastrin

• Status: Completed
• Trial end date: 2010-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Hypergastrinaemia induced by proton pump inhibitor (PPI) treatment is reported to cause ECL-cell and parietal-cell hyperplasia, and rebound hyperacidity and dyspepsia after PPI withdrawal.

The objective of the study was to determine the dosage regimen of netazepide, a gastrin/CCK2 receptor antagonist, required to inhibit the trophic effects of PPI-induced hypergastrinaemia.

Six groups of 8 healthy subjects participated in a randomised, double-blind, placebo-controlled exploratory study of esomeprazole 40 mg daily for 28 days, and netazepide 1, 5 or 25 mg, or placebo daily during the last 14 days of esomeprazole dosing, or 14 days after esomeprazole withdrawal. Serum gastrin and plasma chromogranin A (CgA) were measured regularly from study start until at least 1 week after the last dose. Dyspepsia was monitored after esomeprazole withdrawal.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Trio Medicines Ltd.
• Treatments: Esomeprazole; Gastrins

Criteria

Inclusion Criteria:

1. Healthy men, post-menopausal women or pre-menopausal women, using one of the following methods of contraception: abstinence; condom and spermicide; intra-uterine device; or hysterectomy or tubal ligation

2. Age 18-75 years

3. A body mass index (Quetelet index) in the range 18.0-30.9 Body Mass Index = weight (kg)/height (m2)

4. Negative test for H. pylori

5. No history of dyspepsia symptoms

6. No history of peptic ulcer or oesophagitis

7. No history of treatment with a histamine H2 antagonist, proton pump inhibitor or antacid

8. Normal serum gastrin (no greater than 5% above the upper limit of the HMR laboratory reference range for gastrin)

9. Non-smokers or social smokers (defined as 10 or fewer cigarettes per week)

10. Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial

11. Willingness to give written consent to participate after reading the Information and Consent Form, and after having the opportunity to discuss the trial with the investigator or delegate.

Exclusion Criteria:

1. Women who are pregnant or lactating.

2. Clinically relevant abnormal history, physical findings, ECG (> 450 msec), or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.

3. Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous.

4. Severe adverse reaction to any drug

5. Use, during the 14 days before the baseline visit, of a prescription medicine, especially one that inhibits or induces CYP3A4/5, CYP2C8 or CYP2C9, a hormone contraceptive and hormone replacement therapy.

6. Use, during the 14 days before the baseline visit, of herbal products, such as St John's wort.

7. Use of an over-the-counter medicine during the 7 days before the baseline visit, with the exception of paracetamol (up to 4 g daily).

8. Participation in another trial of a new chemical entity or a prescription medicine, or loss of more than 400 mL blood, within the previous 3 months.

9. Presence or history of drug or alcohol abuse.