YF476 and Type I Gastric Carcinoids (Norway)

Study Overview
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Brief Summary
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The aim of the study is to find out if the experimental medicine, YF476, can make gastric carcinoids, a rare type of stomach tumour, shrink and disappear. Gastric carcinoids occur mainly in patients with chronic atrophic gastritis (CAG), a condition in which the acid-producing cells in the lining of the stomach can't make acid. Acid production is controlled by gastrin, a hormone (chemical messenger) that's released into the bloodstream. If the stomach can't make acid, blood levels of gastrin rise. High blood levels of gastrin in patients with CAG can cause other cells (ECL cells) in the lining of the stomach to grow and, over the years, to give rise to gastric carcinoids. Gastric carcinoids are usually benign, but they can become malignant. Therefore, patients with CAG and gastric carcinoids have the inside of their stomach checked regularly, by gastroscopy, to see if the gastric carcinoids need removing surgically. A gastroscope is a thin (1 cm), flexible tube at end of which is a mini video camera, which enables the user to inspect the lining of the stomach and a 'snare' to take samples of tissue (biopsies). YF476 (netazepide) is a gastrin receptor antagonist (blocks the effects of gastrin), so it's a potential new medical treatment for gastric carcinoids in patients with CAG. Up to 10 of these patients will take YF476 daily for up to 12 weeks. They'll make up to seven outpatient visits for tests, including checks on the safety of YF476 and up to four gastroscopies. At each gastroscopy, the gastric carcinoids will be measured and biopsies taken for laboratory tests. Patients will take up to 24 weeks to finish the study.

Official Title
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A Single Centre, Pilot Trial of YF476 in Patients With Chronic Atrophic Gastritis, Hypergastrinaemia and Type I Gastric Carcinoids

Conditions
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Chronic Atrophic Gastritis, Hypergastrinemia, Type I Gastric Carcinoids

Intervention / Treatment
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* Drug: YF476


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients known to have gastric carcinoids associated with chronic atrophic gastritis and hypergastrinaemia, and who attend the outpatient clinic of the investigator; Men, postmenopausal women, premenopausal women who have been sterilised by tubal ligation, hysterectomy or bilateral oophorectomy, or premenopausal women using reliable contraception: condom and spermicide or intrauterine device; Adults ≥ 18 years; Good general health; and Able to give fully-informed, written consent. Exclusion Criteria: Women who are pregnant, lactating or using a steroid contraceptive; History of gastric surgery, apart from surgery for gastric carcinoids; Evidence of Zollinger-Ellison syndrome; Prolonged QTc interval (>450 msec); Certain medicines and herbal remedies taken during the 7 days before visit 1; Previous treatment with somatostatin; or Participation in other clinical trials of unlicensed medicines within the previous 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YF476<br> | Drug: YF476<br>* 50 mg once daily for 12 weeks, with the option to increase to 75 mg or 100 mg once daily after 6 weeks, or decrease to 25 mg once daily, depending on response.<br>* Other names: netazepide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual assessment of the number of gastric carcinoids. |  | 2 years | 
| Visual assessment of the size of gastric carcinoids |  | 2 years | 
| Visual assessment of the distribution of gastric carcinoids. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of YF476, as judged by medical examinations, vital signs, ECG, safety tests of blood and urine, and adverse events. |  | 2 years | 
| Histologic grading of biopsies. |  | 2 years | 
| Plasma concentrations of YF476. |  | 2 years | 
| Plasma or serum concentrations of biomarkers such as gastrin and chromogranin A (CgA) |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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YF476, netazepide, hypergastrinaemia, gastric carcinoids