YF476 and Type II Gastric Carcinoids
- Registration Number
- NCT02454075
- Lead Sponsor
- Trio Medicines Ltd.
- Brief Summary
This study will evaluate whether treatment with YF476 is safe and effective in reducing the size of type II gastric carcinoid tumours, or limiting the abnormal growth of gastric ECL cells, in patients with Zollinger-Ellison syndrome.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Eligible patients YF476 The dose will be 100 mg YF476 once daily. When 6 patients have completed 12 weeks' treatment with that dose, it may be increased to 150 or 200 mg once daily. Patients will have type II gastric carcinoids and/or ECL cell hyperplasia/dysplasia.
- Primary Outcome Measures
Name Time Method Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy Week 12 visit Regression is defined as a 25% reduction in the size / number of endoscopically evident type II gastric carcinoids. For each participant, three gastric carcinoids were identified and measured at baseline. The same gastric carcinoids were then measured at the Week 12 visit and the percentage difference in size from baseline calculated. The mean percentage change of the three gastric carcinoids per participant is recorded.
A Reduction of 25% in the Gastric ECL Cell Density. Week 12 visit A reduction of 25% in the gastric ECL cell density.
- Secondary Outcome Measures
Name Time Method Improvement in Histological Grade of Gastric Carcinoids/ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy Week 12 visit Reduction in the histological grade of the carcinoids/hyperplasia when compared to baseline.
Decrease in ECL Cell-specific Products Assessed by Quantitative PCR Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) Assessed by quantitative PCR.
Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) Assessed by the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) instrument. Patients assessed a total of 10 symptoms on a scale of 0-5 where: 0 = no symptoms; 1 = symptoms noticeable, but not bothersome; 2 = symptoms noticeable and bothersome, but not every day; 3 = symptoms bothersome everyday; 4 = symptoms affect daily activities; and 5 = symptoms are incapacitating (unable to do daily activities). The total score was summed and reported. The maximum obtainable total score was 50 and minimum obtainable total score was 0, with higher scores indicating a worse outcome and lower scores indicating a better outcome.
Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) The level of a key biomarker chromogranin A (CgA) that is circulating in the blood was measured.
Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate Week 2 visit (baseline) and Week 6 visit Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
1. Volume of aspirate (mL)
2. Acid in aspirate (mEq)
3. Acid output (mEq)Safety and Tolerability Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) Assessed by monitoring adverse events reported by patients
Circulating Plasma Concentration of Gastrin Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) The level of gastrin biomarkers circulating in the blood was measured.
Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate Week 2 visit (baseline) and Week 6 visit Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
1. Volume of aspirate (mL)
2. Acid in aspirate (mEq)
3. Acid output (mEq)Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output Week 2 visit (baseline) and Week 6 visit Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
1. Volume of aspirate (mL)
2. Acid in aspirate (mEq)
3. Acid output (mEq)