Zollinger-Ellison Syndrome
Conditions
Keywords
YF476, netazepide, gastric carcinoids, Zollinger-Ellison syndrome
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.
Interventions
DRUGYF476
Gastrin receptor antagonist
Sponsors
National Institutes of Health (NIH)
Trio Medicines Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men; post-menopausal women; pre-menopausal women who have been sterilised by tubal ligation, hysterectomy or bilateral oophorectomy; or pre-menopausal women using one of the allowed methods of contraception: condom and spermicide or intra-uterine device. 2. Patients with serum gastrin \>250 pg/mL. 3. Hepatic function: AST and ALT ≤2.0 x ULN; total bilirubin ≤1.0 x ULN. 4. Renal function: serum creatinine \<1.0 x ULN. 5. Haematologic function: Hb ≥10.0 g/dL; WBC ≥3.5 x 10e9 /L; ANC ≥1.5 x 10e9 /L; platelets ≥100 x 10e9 /L. 6. Coagulation parameters: INR or PT ≤1.0 x ULN; PTT ≤1.0 x ULN. 7. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial. 8. Willingness to give fully-informed, written consent.
Exclusion criteria
1. Patients under 18 years. 2. Women who are pregnant, lactating or using a steroid contraceptive. 3. Prior gastric resection or bypass. 4. Planned gastrinoma resection during the study period. 5. Patients on somatostatin analogues, except for those on therapy for \>6 months with stable or worsening carcinoids. 6. Inability to tolerate endoscopy, or refusal of endoscopy. 7. Physical findings, ECG (especially prolonged QTc interval \>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. 8. Certain medicines and herbal remedies taken during the 7 days before visit 2. 9. Participation in a trial of an IMP within the previous 28 days. 10. Presence of drug or alcohol abuse. 11. History or baseline findings of: * type 1 diabetes mellitus; * pancreatitis (baseline amylase and/or \>2.0 x ULN); * hepatitis B, hepatitis C or HIV; * malabsorption syndrome or inability to swallow or retain oral medicine; * major surgery \<28 days prior to enrolment; * ECOG performance status \>2; or * another cancer within 3 years except for basal carcinoma of the skin or cervical carcinoma in-situ. * Also, any clinically significant and uncontrolled major morbidity including but not limited to; serious cardiac disease (unstable angina, s/p myocardial infarction \<1 month); respiratory disease (advanced COPD or pulmonary fibrosis); uncontrolled hypertension; or active systemic infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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. |
| 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. |
| 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) |
| 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 |
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eligible Patients 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.
YF476: Gastrin receptor antagonist | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Eligible Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 3 participants |
| Serum chromagraninA (CgA) Patient 01 | 3410 ng/mL |
| Serum chromagraninA (CgA) Patient 02 | 11200 ng/mL |
| Serum chromagraninA (CgA) Patient 03 | 2430 ng/mL |
| Serum gastrin Patient 01 | 587 pg/mL |
| Serum gastrin Patient 02 | 11348 pg/mL |
| Serum gastrin Patient 03 | 1393 pg/mL |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
| Size of gastric carcinoids Patient 01 | 54.79 mm^2 |
| Size of gastric carcinoids Patient 02 | 70.20 mm^2 |
| Size of gastric carcinoids Patient 03 | 24.77 mm^2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
A Reduction of 25% in the Gastric ECL Cell Density.
A reduction of 25% in the gastric ECL cell density.
Time frame: Week 12 visit
Population: Due to the early termination of the study, the data for this outcome measure were not collected.
Primary
Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
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.
Time frame: Week 12 visit
Population: The mean percentage decrease in three gastric carcinoids (measured at Week 12 visit) compared with baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eligible Patients | Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy | Patient 01, Week 12 visit | 23.7 percentage decrease in carcinoid size | Standard Deviation 6.23 |
| Eligible Patients | Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy | Patient 02, Week 12 visit | 8.6 percentage decrease in carcinoid size | Standard Deviation 26.96 |
| Eligible Patients | Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy | Patient 03, Week 12 visit | 10.8 percentage decrease in carcinoid size | Standard Deviation 24.44 |
Secondary
Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate
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)
Time frame: Week 2 visit (baseline) and Week 6 visit
Population: Patients had the volume of gastric aspirate measured at Week 2 and Week 6 visit, by either nasogastric tube (NGT; Patient 01 and Patient 02) or endoscopic gastric analysis (EGA; Patient 03). Data is provided for each visit and participant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 01, Week 2 visit, Day 1, 0 - 15 min | 12 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 01, Week 2 visit, Day 1, 15 - 30 min | 10 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 01, Week 2 visit, Day 1, 30 - 45 min | 4 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 01, Week 2 visit, Day 1, 45 - 60 min | 15 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 01, Week 6 visit, Day 1, 0 - 15 min | 5 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 01, Week 6 visit, Day 1, 15 - 30 min | 7 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 01, Week 6 visit, Day 1, 30 - 45 min | 17 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 01, Week 6 visit, Day 1, 45 - 60 min | 7 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 02, Week 2 visit, Day 1, 0 - 15 min | 10 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 02, Week 2 visit, Day 1, 15 - 30 min | 5 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 02, Week 2 visit, Day 1, 30 - 45 min | 40 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 02, Week 2 visit, Day 1, 45 - 60 min | 25 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 02, Week 6 visit, Day 1, 0 - 15 min | 30 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 02, Week 6 visit, Day 1, 15 - 30 min | 50 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 02, Week 6 visit, Day 1, 30 - 45 min | 10 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 02, Week 6 visit, Day 1, 45 - 60 min | 10 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 02, Week 6 visit, Day 1, 60 - 75 min | 49 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 03, Week 2 visit, Day 1, 0 - 15 min | 15 mL |
| Eligible Patients | Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate | Patient 03, Week 6 visit, Day 1, 0 - 15 min | 17 mL |
Secondary
Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate
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)
Time frame: Week 2 visit (baseline) and Week 6 visit
Population: Patients had the acid content in gastric aspirate measured at Week 2 and Week 6 visit, by either nasogastric tube (NGT; Patient 01 and Patient 02) or endoscopic gastric analysis (EGA; Patient 03). Data is provided for each visit and participant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 01, Week 2 visit, Day 1, 0 - 15 min | 5.6 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 01, Week 2 visit, Day 1, 15 - 30 min | 4.9 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 01, Week 2 visit, Day 1, 30 - 45 min | 5.1 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 01, Week 2 visit, Day 1, 45 - 60 min | 4.9 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 01, Week 6 visit, Day 1, 0 - 15 min | 6.9 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 01, Week 6 visit, Day 1, 15 - 30 min | 6.5 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 01, Week 6 visit, Day 1, 30 - 45 min | 6.6 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 01, Week 6 visit, Day 1, 45 - 60 min | 6.7 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 02, Week 2 visit, Day 1, 0 - 15 min | 6.7 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 02, Week 2 visit, Day 1, 15 - 30 min | 7.4 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 02, Week 2 visit, Day 1, 30 - 45 min | 7.0 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 02, Week 2 visit, Day 1, 45 - 60 min | 7.6 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 02, Week 6 visit, Day 1, 0 - 15 min | 1.2 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 02, Week 6 visit, Day 1, 15 - 30 min | 1.2 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 02, Week 6 visit, Day 1, 30 - 45 min | 1.2 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 02, Week 6 visit, Day 1, 45 - 60 min | 1.2 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 02, Week 6 visit, Day 1, 60 - 75 min | 1.2 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 03, Week 2 visit, Day 1, 0 - 15 min | 4.9 mEq |
| Eligible Patients | Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate | Patient 03, Week 6 visit, Day 1, 0 - 15 min | 1.1 mEq |
Secondary
Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output
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)
Time frame: Week 2 visit (baseline) and Week 6 visit
Population: Patients had acid output measured at Week 2 and Week 6 visit, by either nasogastric tube (NGT; Patient 01 and Patient 02) or endoscopic gastric analysis (EGA; Patient 03). Data is provided for each visit and participant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 01, Week 2 visit, Day 1, 0 - 15 min | 0.1 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 01, Week 2 visit, Day 1, 15 - 30 min | 0 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 01, Week 2 visit, Day 1, 30 - 45 min | 0 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 01, Week 2 visit, Day 1, 45 - 60 min | 0.2 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 01, Week 6 visit, Day 1, 0 - 15 min | 0 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 01, Week 6 visit, Day 1, 15 - 30 min | 0 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 01, Week 6 visit, Day 1, 30 - 45 min | 0 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 01, Week 6 visit, Day 1, 45 - 60 min | 0 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 02, Week 2 visit, Day 1, 0 - 15 min | 0.2 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 02, Week 2 visit, Day 1, 15 - 30 min | 0 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 02, Week 2 visit, Day 1, 30 - 45 min | 0.7 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 02, Week 2 visit, Day 1, 45 - 60 min | 0.4 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 02, Week 6 visit, Day 1, 0 - 15 min | 1.8 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 02, Week 6 visit, Day 1, 15 - 30 min | 4.1 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 02, Week 6 visit, Day 1, 30 - 45 min | 1.2 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 02, Week 6 visit, Day 1, 45 - 60 min | 0.7 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 02, Week 6 visit, Day 1, 60 - 75 min | 1.6 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 03, Week 2 visit, Day 1, 0 - 15 min | 1.2 mEq |
| Eligible Patients | Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output | Patient 03, Week 6 visit, Day 1, 0 - 15 min | 4.6 mEq |
Secondary
Circulating Plasma Concentration of Gastrin
The level of gastrin biomarkers circulating in the blood was measured.
Time frame: Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Population: Data is provided for each visit of each patient. Follow up data is missing for Patient 03 (samples were taken but results not provided).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eligible Patients | Circulating Plasma Concentration of Gastrin | Patient 01, Week 6 visit | 509 pg/mL |
| Eligible Patients | Circulating Plasma Concentration of Gastrin | Patient 01, Week 12 visit | 355 pg/mL |
| Eligible Patients | Circulating Plasma Concentration of Gastrin | Patient 01, Follow-up | 1105 pg/mL |
| Eligible Patients | Circulating Plasma Concentration of Gastrin | Patient 02, Week 6 visit | 13049 pg/mL |
| Eligible Patients | Circulating Plasma Concentration of Gastrin | Patient 02, Week 12 visit | 12846 pg/mL |
| Eligible Patients | Circulating Plasma Concentration of Gastrin | Patient 02, Follow-up | 14113 pg/mL |
| Eligible Patients | Circulating Plasma Concentration of Gastrin | Patient 03, Week 6 | 706 pg/mL |
| Eligible Patients | Circulating Plasma Concentration of Gastrin | Patient 03, Week 12 | 718 pg/mL |
Secondary
Decrease in ECL Cell-specific Products Assessed by Quantitative PCR
Assessed by quantitative PCR.
Time frame: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Population: Data was not collect due to early termination of the study.
Secondary
Improvement in Histological Grade of Gastric Carcinoids/ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
Reduction in the histological grade of the carcinoids/hyperplasia when compared to baseline.
Time frame: Week 12 visit
Population: Due to the early termination of the study, the data for this outcome measure were not collected.
Secondary
Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument
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.
Time frame: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Population: For each patient, the total score on the GERD-HRQL assessment questionnaire at each visit was summed and reported. Data is provided for each visit and participant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 1, Week 2 visit | 3 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 1, Week 6 visit | 3 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 1, Week 12 visit | 2 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 1, Follow up visit | 4 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 2, Week 2 visit | 0 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 2, Week 6 visit | 26 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 2, Week 12 visit | 10 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 2, Follow up visit | 19 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 3, Week 2 visit | 0 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 3, Week 6 visit | 0 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 3, Week 12 visit | 0 score on a scale |
| Eligible Patients | Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument | Patient 3, Follow up visit | 0 score on a scale |
Secondary
Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples
The level of a key biomarker chromogranin A (CgA) that is circulating in the blood was measured.
Time frame: Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Population: The CgA data is provided for each participant at each visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eligible Patients | Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples | Patient 01, Week 6 visit | 2600 ng/mL |
| Eligible Patients | Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples | Patient 01, Week 12 visit | 2700 ng/mL |
| Eligible Patients | Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples | Patient 01, Follow-up | 12300 ng/mL |
| Eligible Patients | Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples | Patient 02, Week 6 visit | 11950 ng/mL |
| Eligible Patients | Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples | Patient 02, Week 12 visit | 15350 ng/mL |
| Eligible Patients | Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples | Patient 02, Follow up | 24100 ng/mL |
| Eligible Patients | Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples | Patient 03, Week 6 visit | 213 ng/mL |
| Eligible Patients | Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples | Patient 03, Week 12 visit | NA ng/mL |
| Eligible Patients | Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples | Patient 03, Follow-up | NA ng/mL |
Secondary
Safety and Tolerability
Assessed by monitoring adverse events reported by patients
Time frame: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eligible Patients | Safety and Tolerability | Week 2 visit: number of treatment related adverse events | 0 adverse events |
| Eligible Patients | Safety and Tolerability | Week 6 visit: number of treatment related adverse events | 0 adverse events |
| Eligible Patients | Safety and Tolerability | Week 12 visit: number of treatment related adverse events | 0 adverse events |
| Eligible Patients | Safety and Tolerability | Follow up visit: number of treatment related adverse events | 0 adverse events |