Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 11-DK-0114 | Other Identifier | NIHR |
Not provided
Not provided
Not provided
Poor recruitment
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
Not provided
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eligible patients | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| YF476 | Drug | Gastrin receptor antagonist |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Week 12 visit |
| A Reduction of 25% in the Gastric ECL Cell Density. | A reduction of 25% in the gastric ECL cell density. | Week 12 visit |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Week 12 visit |
| Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples |
Not provided
Inclusion criteria:
Exclusion criteria:
Patients under 18 years.
Women who are pregnant, lactating or using a steroid contraceptive.
Prior gastric resection or bypass.
Planned gastrinoma resection during the study period.
Patients on somatostatin analogues, except for those on therapy for >6 months with stable or worsening carcinoids.
Inability to tolerate endoscopy, or refusal of endoscopy.
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.
Certain medicines and herbal remedies taken during the 7 days before visit 2.
Participation in a trial of an IMP within the previous 28 days.
Presence of drug or alcohol abuse.
History or baseline findings of:
Not provided
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| ID | Title | Description |
|---|---|---|
| FG000 | Eligible Patients | Patients received 100 mg YF476 orally once daily for 12 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The mean percentage decrease in three gastric carcinoids (measured at Week 12 visit) compared with baseline. | Posted | Mean | Standard Deviation | percentage decrease in carcinoid size | Week 12 visit |
|
12 weeks
Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with that treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Eligible Patients | The dose will be an oral dose of 100 mg YF476 once daily. for 12 weeks. 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 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Toothache | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Malcolm Boyce | Trio Medicines | 020 8961 4130 | mboyce@hmrlondon.com |
Not provided
| ID | Term |
|---|---|
| D015043 | Zollinger-Ellison Syndrome |
| ID | Term |
|---|---|
| D009384 | Paraneoplastic Endocrine Syndromes |
| D010257 | Paraneoplastic Syndromes |
| D009369 | Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C104428 | YF 476 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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Not provided
The level of a key biomarker chromogranin A (CgA) that is circulating in the blood was measured. |
| Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) |
| 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:
| Week 2 visit (baseline) and Week 6 visit |
| Decrease in ECL Cell-specific Products Assessed by Quantitative PCR | Assessed by quantitative PCR. | Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) |
| 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. | Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) |
| Safety and Tolerability | Assessed by monitoring adverse events reported by patients | Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) |
| Circulating Plasma Concentration of Gastrin | The level of gastrin biomarkers circulating in the blood was measured. | Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) |
| 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:
| Week 2 visit (baseline) and Week 6 visit |
| 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:
| Week 2 visit (baseline) and Week 6 visit |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Serum gastrin | Measured on screening visit | Number | pg/mL |
|
| Serum chromagraninA (CgA) | Measured pre-dose on Day 1, Visit 2 | Number | ng/mL |
|
| Size of gastric carcinoids | Measured via endoscopy on Visit 2 | Mean | Full Range | mm^2 |
|
|
|
| Primary | A Reduction of 25% in the Gastric ECL Cell Density. | A reduction of 25% in the gastric ECL cell density. | Due to the early termination of the study, the data for this outcome measure were not collected. | Posted | Week 12 visit |
|
|
| 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. | Due to the early termination of the study, the data for this outcome measure were not collected. | Posted | Week 12 visit |
|
|
| 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. | The CgA data is provided for each participant at each visit | Posted | Number | ng/mL | Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) |
|
|
|
| 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:
| 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. | Posted | Number | mL | Week 2 visit (baseline) and Week 6 visit |
|
|
|
| Secondary | Decrease in ECL Cell-specific Products Assessed by Quantitative PCR | Assessed by quantitative PCR. | Data was not collect due to early termination of the study. | Posted | Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) |
|
|
| 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. | 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. | Posted | Number | score on a scale | Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) |
|
|
|
| Secondary | Safety and Tolerability | Assessed by monitoring adverse events reported by patients | Posted | Number | adverse events | Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) |
|
|
|
| Secondary | Circulating Plasma Concentration of Gastrin | The level of gastrin biomarkers circulating in the blood was measured. | Data is provided for each visit of each patient. Follow up data is missing for Patient 03 (samples were taken but results not provided). | Posted | Number | pg/mL | Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment) |
|
|
|
| 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:
| 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. | Posted | Number | mEq | Week 2 visit (baseline) and Week 6 visit |
|
|
|
| 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:
| 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. | Posted | Number | mEq | Week 2 visit (baseline) and Week 6 visit |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 3 |
| 3 |
| Stomach pain | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Upper respiratory tract infections | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
Not provided
Not provided
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D010437 | Peptic Ulcer |
| D004378 | Duodenal Diseases |
| D007410 | Intestinal Diseases |
| D013272 | Stomach Diseases |
|
| Patient 01, Follow-up |
|
|
| Patient 02, Week 6 visit |
|
|
| Patient 02, Week 12 visit |
|
|
| Patient 02, Follow up |
|
|
| Patient 03, Week 6 visit |
|
|
| Patient 03, Week 12 visit |
|
|
| Patient 03, Follow-up |
|
|
|
| Patient 01, Week 2 visit, Day 1, 30 - 45 min |
|
|
| Patient 01, Week 2 visit, Day 1, 45 - 60 min |
|
|
| Patient 01, Week 6 visit, Day 1, 0 - 15 min |
|
|
| Patient 01, Week 6 visit, Day 1, 15 - 30 min |
|
|
| Patient 01, Week 6 visit, Day 1, 30 - 45 min |
|
|
| Patient 01, Week 6 visit, Day 1, 45 - 60 min |
|
|
| Patient 02, Week 2 visit, Day 1, 0 - 15 min |
|
|
| Patient 02, Week 2 visit, Day 1, 15 - 30 min |
|
|
| Patient 02, Week 2 visit, Day 1, 30 - 45 min |
|
|
| Patient 02, Week 2 visit, Day 1, 45 - 60 min |
|
|
| Patient 02, Week 6 visit, Day 1, 0 - 15 min |
|
|
| Patient 02, Week 6 visit, Day 1, 15 - 30 min |
|
|
| Patient 02, Week 6 visit, Day 1, 30 - 45 min |
|
|
| Patient 02, Week 6 visit, Day 1, 45 - 60 min |
|
|
| Patient 02, Week 6 visit, Day 1, 60 - 75 min |
|
|
| Patient 03, Week 2 visit, Day 1, 0 - 15 min |
|
|
| Patient 03, Week 6 visit, Day 1, 0 - 15 min |
|
|
|
| Patient 1, Week 12 visit |
|
|
| Patient 1, Follow up visit |
|
|
| Patient 2, Week 2 visit |
|
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| Patient 2, Week 6 visit |
|
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| Patient 2, Week 12 visit |
|
|
| Patient 2, Follow up visit |
|
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| Patient 3, Week 2 visit |
|
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| Patient 3, Week 6 visit |
|
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| Patient 3, Week 12 visit |
|
|
| Patient 3, Follow up visit |
|
|
|
| Follow up visit: number of treatment related adverse events |
|
|
| Patient 01, Follow-up |
|
|
| Patient 02, Week 6 visit |
|
|
| Patient 02, Week 12 visit |
|
|
| Patient 02, Follow-up |
|
|
| Patient 03, Week 6 |
|
|
| Patient 03, Week 12 |
|
|
|
| Patient 01, Week 2 visit, Day 1, 30 - 45 min |
|
|
| Patient 01, Week 2 visit, Day 1, 45 - 60 min |
|
|
| Patient 01, Week 6 visit, Day 1, 0 - 15 min |
|
|
| Patient 01, Week 6 visit, Day 1, 15 - 30 min |
|
|
| Patient 01, Week 6 visit, Day 1, 30 - 45 min |
|
|
| Patient 01, Week 6 visit, Day 1, 45 - 60 min |
|
|
| Patient 02, Week 2 visit, Day 1, 0 - 15 min |
|
|
| Patient 02, Week 2 visit, Day 1, 15 - 30 min |
|
|
| Patient 02, Week 2 visit, Day 1, 30 - 45 min |
|
|
| Patient 02, Week 2 visit, Day 1, 45 - 60 min |
|
|
| Patient 02, Week 6 visit, Day 1, 0 - 15 min |
|
|
| Patient 02, Week 6 visit, Day 1, 15 - 30 min |
|
|
| Patient 02, Week 6 visit, Day 1, 30 - 45 min |
|
|
| Patient 02, Week 6 visit, Day 1, 45 - 60 min |
|
|
| Patient 02, Week 6 visit, Day 1, 60 - 75 min |
|
|
| Patient 03, Week 2 visit, Day 1, 0 - 15 min |
|
|
| Patient 03, Week 6 visit, Day 1, 0 - 15 min |
|
|
| Title | Measurements |
|---|---|
|
| Patient 01, Week 2 visit, Day 1, 45 - 60 min |
|
| Patient 01, Week 6 visit, Day 1, 0 - 15 min |
|
| Patient 01, Week 6 visit, Day 1, 15 - 30 min |
|
| Patient 01, Week 6 visit, Day 1, 30 - 45 min |
|
| Patient 01, Week 6 visit, Day 1, 45 - 60 min |
|
| Patient 02, Week 2 visit, Day 1, 0 - 15 min |
|
| Patient 02, Week 2 visit, Day 1, 15 - 30 min |
|
| Patient 02, Week 2 visit, Day 1, 30 - 45 min |
|
| Patient 02, Week 2 visit, Day 1, 45 - 60 min |
|
| Patient 02, Week 6 visit, Day 1, 0 - 15 min |
|
| Patient 02, Week 6 visit, Day 1, 15 - 30 min |
|
| Patient 02, Week 6 visit, Day 1, 30 - 45 min |
|
| Patient 02, Week 6 visit, Day 1, 45 - 60 min |
|
| Patient 02, Week 6 visit, Day 1, 60 - 75 min |
|
| Patient 03, Week 2 visit, Day 1, 0 - 15 min |
|
| Patient 03, Week 6 visit, Day 1, 0 - 15 min |
|