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The study was terminated based on interim analysis. See detailed description.
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This is a study designed to evaluate the potential for the pradigastat (LCQ908) to impact cardiovascular risk.
This study had 2 parts. Part A was a multicenter, double-blind, randomized, placebo-controlled, non-confirmatory crossover study assessing response to a high-fat meal challenge in the setting of pradigastat versus placebo. Part A had 2 cohorts i.e. Cohort 1 patients with stable coronary artery disease and hypertriglyceridemia and Cohort 2 patients with asymptomatic non-obstructive coronary artery disease or elevated coronary heart disease risk and hypertriglyceridemia.
Part B was a double blinded phase designed to assess response to three months of chronic treatment with pradigastat versus placebo on a normal diet.
The trial was terminated after the interim analysis of Part A, Cohort 1. The interim analysis results indicated that the high-fat meal challenge did not induce any impairment on either myocardial perfusion reserve index (MPRi) or exercise treadmill performance. Part B was never started.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pradigastat (LCQ908) followed by placebo | Experimental | Pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment |
|
| Placebo followed by pradigastat (LCQ908) | Experimental | Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by p20 mg (2 x 10-mg tablets) daily for two days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| pradigastat (LCQ908) | Drug | pradigastat tablets were supplied to the investigators at dose strengths of 10 mg and 20 mg as individual patient packs. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Myocardial Perfusion Reserve Index (MPRi) Overall Mean (Part A, Cohort 1) | MPRi (myocardial perfusion reserve index) is a measure of coronary microvascular function. Myocardial perfusion scans using 0.05 mmol/kg of gadolinium contrast were acquired at rest and under stress (pharmacological stress induced with adenosine 140 μg/kg/min for three minutes). An independent central reader performed the cardiac image analysis of all time points including the calculation of the myocardial perfusion reserve index from the ratio of the global stress myocardial blood flow divided by the resting blood flow values. Higher/increased index indicates improved flow/better outcome. This primary endpoint was only for Part A, Cohort 1 patients. | Baseline, and on day 5 of each of the two treatment periods |
| Change From Baseline in Total Exercise Duration (Part A, Cohort 1) | Total exercise duration was the elapsed time between the start of exercise and termination of exercise for severe angina, dyspnea or extreme fatigue. This primary endpoint was only for Part A, Cohort 1 patients. | Baseline and on day 5 of each of the two treatment periods |
| Time to Onset of Angina (Part A, Cohort 1) | Time to onset of angina was defined as the elapsed time between the start of exercise and the onset of anginal chest pain as reported by the patient and recorded by the performing investigator. | Baseline and on day 5 of each of the two treatment periods |
| Time to Onset of Exercise-induced Ischemia(Part A, Cohort 1) | Exercise-induced ischemia was defined as the new development of horizontal or down-sloping ST-segment depression (≥ 1mm at 60 milliseconds after the J point) versus baseline tracings. | Baseline and on day 5 of each of the two treatment periods |
| Aortic Plaque Inflammation (Part B) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (Part A, Cohort 1) | approximately 40 days | |
| Number of Participants With Adverse Events (Part A, Cohort 2) | approximately 40 days | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Pasadena | California | 91105 | United States |
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Study was terminated upon Part A interim analysis. Total 41 patients randomized to Part A i.e.17 patients in cohort 1 and 24 patients in Cohort 2.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo | Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment |
| FG001 | Part A, Cohort 1: Placebo Followed by Pradigastat (LCQ908) | Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by 20 mg (2 x 10-mg tablets) daily for two days |
| FG002 | Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo | Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All patients who randomized to this sequence received pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment |
| FG003 | Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908) | Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by 20 mg (2 x 10-mg tablets) daily for two days |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (5 Days [Day 1 - 5]) |
|
| ||||||||||||||||||
| Treatment Period 2(5 Days[Day 36 - 40]) |
|
The safety analysis set included all patients who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo | Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Change From Baseline in Myocardial Perfusion Reserve Index (MPRi) Overall Mean (Part A, Cohort 1) | MPRi (myocardial perfusion reserve index) is a measure of coronary microvascular function. Myocardial perfusion scans using 0.05 mmol/kg of gadolinium contrast were acquired at rest and under stress (pharmacological stress induced with adenosine 140 μg/kg/min for three minutes). An independent central reader performed the cardiac image analysis of all time points including the calculation of the myocardial perfusion reserve index from the ratio of the global stress myocardial blood flow divided by the resting blood flow values. Higher/increased index indicates improved flow/better outcome. This primary endpoint was only for Part A, Cohort 1 patients. | Efficacy analysis set - Patients who took > 80% of study drug as assessed by drug accountability, had no major protocol deviations, and had a valid assessment of MPRi at both baseline and post-treatment visits. Patients who had no baseline or post-treatment MPRi data in 1 of 2 periods were excluded from the analysis. | Posted | Least Squares Mean | Standard Error | myocardial perfusion reserve index | Baseline, and on day 5 of each of the two treatment periods |
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The safety analysis set included all patients who received at least one dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A, Cohort 1: Pradigastat (LCQ908) | Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received pradigastat in either of 2 treatment period. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Coronary artery disease | Cardiac disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Supraventricular extrasystoles | Cardiac disorders | MedDRA | Systematic Assessment |
The study was terminated based on the interim analysis on Part A, Cohort 1 after patients completed Part A. Part B was not conducted. Not all the planned assessments were completed due to the termination
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | trialandresults.registries@novartis.com |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| D015228 | Hypertriglyceridemia |
| D006949 | Hyperlipidemias |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C000594809 | pradigastat |
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|
| Placebo | Drug | matching placebo tablets |
|
This endpoint was palnned for analysis on Part B patients which was never started becasue study got terminated on Part A interim analysis. |
| Baseline and on treatment day 85 +/- 3 days |
| Postprandial Triglycerides (Part A, Cohort 1) |
For both each treatment period, postprandial triglycerides were measured on Day 5 i.e. on 0 hour(before breakfast), two hours and four hours post high-fat breakfast. Results are from an ANCOVA model on change from baseline in the log domain with log(baseline), treatment, sequence and period as fixed effects. Baseline is the Day -1 value within period. The data reported is ratio of geometric mean between post-treatment and baseline data. |
| 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5 |
| Postprandial Triglycerides (Part A, Cohort 2) | For both each treatment period, postprandial triglycerides were measured on Day 5 i.e. on 0 hour (before breakfast), two hours and four hours post high-fat breakfast. Results are from an ANCOVA model on change from baseline in the log domain with log(baseline), treatment, sequence and period as fixed effects. Baseline is the Day -1 value within period. The data reported is ratio of geometric mean between post-treatment and baseline data. | 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5 |
| Pharmacokinetics of Pradigastat (LCQ908): Plasma Concentration (Part A) | Part A: Day 4 and day 5 of each treatment period |
| Other Related Lipid Parameters (Part A) | Baseline, day 4 and day 5 of each treatment period |
| Interleukin-6 (IL-6) Level (Part A) | Baseline, day 4 and day 5, of each treatment period |
| C-reactive Protein (CRP) Level (Part A) | Baseline, day 4 and day 5, of each treatment period |
| Adiponectin Level ( Part B) | Part B; Baseline, day 15, day 43 and day 85 |
| Withdrawal by Subject |
|
| Protocol deviation |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | Part A, Cohort 1: Placebo Followed by Pradigastat (LCQ908) | Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by 20 mg (2 x 10-mg tablets) daily for two days |
| BG002 | Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo | Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All patients who randomized to this sequence received pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment |
| BG003 | Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908) | Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by 20 mg (2 x 10-mg tablets) daily for two days |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Part A, Cohort 1: Pradigastat (LCQ908) | Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received pradigastat in either of 2 treatment period. |
| OG001 | Part A, Cohort 1: Placebo | Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period |
|
|
| Primary | Change From Baseline in Total Exercise Duration (Part A, Cohort 1) | Total exercise duration was the elapsed time between the start of exercise and termination of exercise for severe angina, dyspnea or extreme fatigue. This primary endpoint was only for Part A, Cohort 1 patients. | Efficacy analysis set- Patients who took > 80% of study drug as assessed by drug accountability, had no major protocol deviations, and had a valid assessment of total exercise duration at both baseline and post-treatment visits. Patients who had no baseline or post-treatment exercise duration data in 1 of 2 periods were excluded from the analysis. | Posted | Least Squares Mean | Standard Error | minute | Baseline and on day 5 of each of the two treatment periods |
|
|
|
| Primary | Time to Onset of Angina (Part A, Cohort 1) | Time to onset of angina was defined as the elapsed time between the start of exercise and the onset of anginal chest pain as reported by the patient and recorded by the performing investigator. | The study was terminated based on the interim analysis after patients completed Part A. This outcome measure was not part of interim analysis; hence it is not done. . | Posted | Baseline and on day 5 of each of the two treatment periods |
|
|
| Primary | Time to Onset of Exercise-induced Ischemia(Part A, Cohort 1) | Exercise-induced ischemia was defined as the new development of horizontal or down-sloping ST-segment depression (≥ 1mm at 60 milliseconds after the J point) versus baseline tracings. | The study was terminated based on the interim analysis after patients completed Part A. This outcome measure was not part of interim analysis; hence it is not done. . | Posted | Baseline and on day 5 of each of the two treatment periods |
|
|
| Primary | Aortic Plaque Inflammation (Part B) | This endpoint was palnned for analysis on Part B patients which was never started becasue study got terminated on Part A interim analysis. | The study was terminated based on the interim analysis after patients completed Part A. Part B of the study was never started. | Posted | Baseline and on treatment day 85 +/- 3 days |
|
|
| Secondary | Number of Participants With Adverse Events (Part A, Cohort 1) | The safety analysis set included all patients who received at least one dose of study drug. | Posted | Number | Participants | approximately 40 days |
|
|
|
| Secondary | Number of Participants With Adverse Events (Part A, Cohort 2) | The safety analysis set included all patients who received at least one dose of study drug. | Posted | Number | Participants | approximately 40 days |
|
|
|
| Secondary | Postprandial Triglycerides (Part A, Cohort 1) | For both each treatment period, postprandial triglycerides were measured on Day 5 i.e. on 0 hour(before breakfast), two hours and four hours post high-fat breakfast. Results are from an ANCOVA model on change from baseline in the log domain with log(baseline), treatment, sequence and period as fixed effects. Baseline is the Day -1 value within period. The data reported is ratio of geometric mean between post-treatment and baseline data. | The efficacy analysis set included all patients who took more than 80% of study medication as assessed by drug accountability, had no major protocol deviations, and had a valid assessment of the primary efficacy variables at both baseline and post treatment visits. | Posted | Geometric Mean | Standard Error | ratio | 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5 |
|
|
|
| Secondary | Postprandial Triglycerides (Part A, Cohort 2) | For both each treatment period, postprandial triglycerides were measured on Day 5 i.e. on 0 hour (before breakfast), two hours and four hours post high-fat breakfast. Results are from an ANCOVA model on change from baseline in the log domain with log(baseline), treatment, sequence and period as fixed effects. Baseline is the Day -1 value within period. The data reported is ratio of geometric mean between post-treatment and baseline data. | The efficacy analysis set included all patients who took more than 80% of study medication as assessed by drug accountability, had no major protocol deviations, and had a valid assessment of the primary efficacy variables at both baseline and post treatment visits. | Posted | Geometric Mean | Standard Error | ratio | 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5 |
|
|
|
| Secondary | Pharmacokinetics of Pradigastat (LCQ908): Plasma Concentration (Part A) | The study was terminated based on the interim analysis on Part A, Cohort 1 after patients completed Part A. The analysis of this assessment was not part of interim analysis; hence it is not done. | Posted | Part A: Day 4 and day 5 of each treatment period |
|
|
| Secondary | Other Related Lipid Parameters (Part A) | The study was terminated based on the interim analysis on Part A, Cohort 1 after patients completed Part A. The analysis of this assessment was not part of interim analysis; hence it is not done. | Posted | Baseline, day 4 and day 5 of each treatment period |
|
|
| Secondary | Interleukin-6 (IL-6) Level (Part A) | The study was terminated based on the interim analysis on Part A, Cohort 1 after patients completed Part A. The analysis of this assessment was not part of interim analysis; hence it is not done. | Posted | Baseline, day 4 and day 5, of each treatment period |
|
|
| Secondary | C-reactive Protein (CRP) Level (Part A) | The study was terminated based on the interim analysis on Part A, Cohort 1 after patients completed Part A. The analysis of this assessment was not part of interim analysis; hence it is not done. | Posted | Baseline, day 4 and day 5, of each treatment period |
|
|
| Secondary | Adiponectin Level ( Part B) | The study was terminated based on the interim analysis on Part A, cohort 1 after patients completed Part A. Part B of the study was not commenced. | Posted | Part B; Baseline, day 15, day 43 and day 85 |
|
|
| 0 |
| 17 |
| 16 |
| 17 |
| EG001 | Part A, Cohort 1: Placebo | Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period | 0 | 17 | 6 | 17 |
| EG002 | Part A, Cohort 2: Pradigastat (LCQ908) | Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All randomized patients who recieved pradigastat in either of 2 treatment period. | 0 | 24 | 22 | 24 |
| EG003 | Part A, Cohort 2: Placebo | Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period | 1 | 24 | 13 | 24 |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Chills | General disorders | MedDRA | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Fibula fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Fracture pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Polyuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Death |
|
| Death |
|
| Day 5 Hr 4 |
|
| Day 5 Hr 4 |
|