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This Phase 2, randomized, open-label, 2-treatment, 2-sequence, 2-period crossover, pharmacokinetic (PK) study will compare plasma concentrations of BH4 in subjects with endothelial dysfunction following 14 days of treatment by each of 2 regimens: sapropterin dihydrochloride with vitamin C and sapropterin dihydrochloride alone.
This was a Phase 2, randomized, open-label, 2-treatment, 2-sequence, 2-period crossover, pharmacokinetic (PK) study designed to compare the plasma concentrations of BH4 in subjects with endothelial dysfunction following 14 days of treatment by each of 2 regimens: sapropterin dihydrochloride with vitamin C and sapropterin dihydrochloride alone. Each subject received each regimen; the 2 treatment groups varied only in the sequence of the 2 regimens. The washout period between treatment regimens comprised the 1 day period between the last dose of study drug under the first regimen and the first dose of study drug under the second regimen (Day 14 morning to Day 15 morning).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sapropterin dihydrochloride | Experimental | Sapropterin dihydrochloride 5 mg/kg twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14 and Day 28. |
|
| Sapropterin dihydrochloride+Vitamin C | Experimental | Sapropterin dihydrochloride 5 mg/kg and 500 mg Vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14 and Day 28. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sapropterin Dihydrochloride | Drug | Sapropterin Dihydrochloride 5 mg/kg twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14 and Day 28. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC0-12hrs) of Plasma BH4 Concentration | Plasma BH4 concentration area under the curve (AUC0-12 hrs) at the end of each regimen in subjects with endothelial dysfunction. | At 30 minutes prior to dosing, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hours after dosing. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC0-12hrs) of Plasma BH2 and B Concentration | Plasma BH2 and B concentration area under the curve (AUC0-12hrs) at the end of each regimen in subjects with endothelial dysfunction. | At 30 minutes prior to dosing, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hours after dosing. |
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Inclusion Criteria:
Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
Age is ≥ 18 years and ≤ 75 years.
Willing and able to comply with all study procedures.
If currently receiving treatment with or taking any of the following supplements, be willing and able to discontinue taking them throughout the treatment period:
History of cardiovascular disease or cardiovascular risk factors, eg, stable and well-controlled Type 2 diabetes, peripheral arterial disease, obesity, smoking, hypercholesterolemia
Endothelial dysfunction, documented at screening by an abnormal peripheral arterial tonometry (PAT) of ≤ 1.70.
Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy.
Exclusion Criteria:
Hypertension secondary to other medical conditions (e.g., renal failure or steroid usage).
Concurrent disease or condition that would interfere with study participation or safety, such as bleeding disorders; history of syncope or vertigo; severe gastroesophageal reflux disease (GERD); heart failure; symptomatic coronary disease; arrhythmia; serious neurologic disorders, including seizures; organ transplant; or organ failure.
Type 2 diabetics that are uncontrolled, unstable, newly diagnosed, or have changed therapy in the last three months and all Type 1 diabetics.
Any severe comorbid condition that would limit life expectancy to < 6 months.
Serum creatinine > 2.0 mg/dL, or hepatic enzyme concentrations > 2 times the upper limit of normal
HIV infection, hepatic cirrhosis, other preexisting liver disease, or positive HIV, Hepatitis B or C test at screening.
Concomitant treatment with:
Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
Myocardial infarction, stroke, or surgery within the last 60 days prior to screening.
History of alcohol and/or drug abuse or a positive alcohol or drug test at screening.
Previous treatment with any formulation of BH4.
Has known hypersensitivity to 6R-BH4 or its excipients.
Pregnant or breastfeeding at screening, or planning to become pregnant (self or partner) at any time during the study.
Any condition that, in the view of the PI, places the subject at high risk of poor treatment compliance or of not completing the study.
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| Name | Affiliation | Role |
|---|---|---|
| Don Nwose, MD | BioMarin Pharmaceutical | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hackensack | New Jersey | United States |
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| Label | URL |
|---|---|
| BioMarin Pharmaceutical Inc. website | View source |
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A total of 52 subjects were randomized into the study and received study drug.
Of these, 4 subjects were enrolled under an earlier version of the protocol that used different eligibility criteria and were monitored according to different data collection procedures.
Only the 48 subjects enrolled under the final protocol were included in the analyses.
This was a single-center study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sapropterin Dihydrochloride 10mg/kg First; Then Sapropterin Dihydrochloride 10mg/kg and Vitamin C | Sequence A: Sapropterin dihydrochloride as the first treatment followed by sapropterin dihydrochloride and vitamin C Treatment Regimen 1: Sapropterin dihydrochloride 5 mg/kg twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14. Treatment Regimen 2: Sapropterin dihydrochloride 5 mg/kg + 500 mg vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 28 The washout period of 1 day comprised between treatment regimens. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period - Day 1 to Day 14 |
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| Sapropterin Dihydrochloride and Vitamin C | Drug | Sapropterin Dihydrochloride 5 mg/kg and 500 mg Vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14 and Day 28. |
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| Area Under the Curve (AUC0-12hours) for Calculated BH4 (From Total Biopterin) |
Total biopterin concentration area under the curve (AUC0-12hours) at the end of each regimen in subjects with endothelial dysfunction is theoretically the sum of BH4, BH2 and B. Biopterin is the metabolite of BH4 after oxidative conversion of BH4 and BH2 to biopterin. Total biopterin concentrations represent the summation of drug and metabolites: BH4, BH2 and B. The total biopterin concentrations can be converted to BH4 concentration using the conversion factor 2.150. |
| At 30 minutes prior to dosing, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hours after dosing. |
| Ratio of BH2, B and BH4 Calculated From Total Biopterin Area Under the Curve (0-12hours) for Subjects Administered Sapropterin Dihydrochloride With Vitamin C to Subjects Administered Sapropterin Alone. | Ratio of Mean AUC (0-12 hours) for subjects receiving (Sapropterin dihydrochloride + Vitamin C)/ Mean AUC (0-12 hours) for subjects receiving Sapropterin dihydrochloride alone) for BH4, BH2, B, BH4/BH2 Ratio, and BH4 Calculated from Total Biopterin. | At 30 minutes prior to dosing, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hours after dosing. |
| Change From Baseline in Peripheral Arterial Tonometry (PAT) | PAT measures pulse wave amplitude of the small arteries of the finger as a surrogate to assess endothelial function and arterial stiffness using a finger plethysmographic probe and 5-minute occlusion of the brachial artery. Endothelial dysfunction, a protocol inclusion criteria, is defined by an abnormal PAT of < or = 1.70. Change is calculated as follows: end time measurement - starting time measurement. | At Baseline, Day 13 and Day 27 |
| Change From Baseline in Systolic Blood Pressure (SBP) | Change is calculated as follows: end time measurement - starting time measurement. Mean daytime systolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) | At Baseline, Day 13 and Day 27 |
| Change From Baseline in Diastolic Blood Pressure (DBP) | Change is calculated as follows: end time measurement - starting time measurement. Mean daytime diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) | At Baseline, Day 13 and Day 27 |
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. | Up to 56 ± 3 Days. |
| Change From Baseline in Urinary 8-isoprostane/Creatinine | Biomarkers of endothelial function, oxidative stress, and inflammation as measured by 8-isoprostane. | At Baseline, Day 14 and Day 28 |
| Change From Baseline in Cyclic Guanosine Monophosphate (cGMP) | Biomarkers of endothelial function, oxidative stress, and inflammation as measured by cyclic guanosine monophosphate (cGMP). | At Baseline, Day 14 and Day 28. |
| Change in Urinary Albumin to Creatinine Ratio (mg/g) | Change in Urinary Albumin to Creatinine Ratio (mg/g) from Baseline to Day 14, Baseline to Day 28, and from Day 14 to Day 28 | Baseline, Day 14 and Day 28 |
| Number of Participants With Urinary Albumin to Creatinine Ratio <30 mg/g | Summary of Urinary Albumin to Creatinine Ratio (mg/g) by subjects with ratio <30 mg/g and subjects with ratios >=30 mg/g at Baseline, Day 14 and Day 28 | Baseline, Day 14 and Day 28 |
| FG001 | Sapropterin Dihydrochloride 10mg/kg and Vitamin C First; Then Sapropterin Dihydrochloride 10mg/kg | Sequence B: Sapropterin dihydrochloride and vitamin C as the first treatment followed by sapropterin dihydrochloride. Treatment Regimen 2: Sapropterin dihydrochloride 5 mg/kg + 500 mg vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14. Treatment Regimen 1: Sapropterin dihydrochloride 5 mg/kg twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal Day 28. The washout period of 1 day comprised between treatment regimens. |
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| NOT COMPLETED |
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| Washout (1 Day) |
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| Treatment Period - Day 15 to Day 28 |
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Four subjects, were enrolled prior to change in the study design from a parallel to a crossover study. These four subjects were not included in the baseline analysis population as they only received one treatment (either sapropterin dihydrochloride alone or sapropterin dihydrochloride and vitamin C) for the full 29-day duration of the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sapropterin Dihydrochloride 10mg/kg First, Then Sapropterin Dihydrochloride 10mg/kg and Vitamin C | Sequence A: Sapropterin dihydrochloride as the first treatment followed by sapropterin dihydrochloride and vitamin C Treatment Regimen 1: Sapropterin dihydrochloride 5 mg/kg twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14. Treatment Regimen 2: Sapropterin dihydrochloride 5 mg/kg + 500 mg vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 28 The washout period of 1 day comprised between treatment regimens. |
| BG001 | Sapropterin Dihydrochloride 10mg/kg and Vitamin C First, Then Sapropterin Dihydrochloride 10mg/kg | Sequence B: Sapropterin dihydrochloride and vitamin C as the first treatment followed by sapropterin dihydrochloride Treatment Regimen 2: Sapropterin dihydrochloride 5 mg/kg + 500 mg vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14. Treatment Regimen 1: Sapropterin dihydrochloride 5 mg/kg twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal Day 28. The washout period of 1 day comprised between treatment regimens. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Age | Count of Participants | Participants |
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| Race | Count of Participants | Participants |
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| Ethnicity | Count of Participants | Participants |
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| Weight | Mean | Standard Deviation | kg |
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| Height | Mean | Standard Deviation | cm |
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| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Area Under the Curve (AUC0-12hrs) of Plasma BH4 Concentration | Plasma BH4 concentration area under the curve (AUC0-12 hrs) at the end of each regimen in subjects with endothelial dysfunction. | Intent-to-treat (ITT) Population | Posted | Mean | Standard Deviation | nM*hr | At 30 minutes prior to dosing, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hours after dosing. |
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| Secondary | Area Under the Curve (AUC0-12hrs) of Plasma BH2 and B Concentration | Plasma BH2 and B concentration area under the curve (AUC0-12hrs) at the end of each regimen in subjects with endothelial dysfunction. | ITT population | Posted | Mean | Standard Deviation | nM*hr | At 30 minutes prior to dosing, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hours after dosing. |
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| Secondary | Area Under the Curve (AUC0-12hours) for Calculated BH4 (From Total Biopterin) | Total biopterin concentration area under the curve (AUC0-12hours) at the end of each regimen in subjects with endothelial dysfunction is theoretically the sum of BH4, BH2 and B. Biopterin is the metabolite of BH4 after oxidative conversion of BH4 and BH2 to biopterin. Total biopterin concentrations represent the summation of drug and metabolites: BH4, BH2 and B. The total biopterin concentrations can be converted to BH4 concentration using the conversion factor 2.150. | ITT population | Posted | Mean | Standard Deviation | nM*hr | At 30 minutes prior to dosing, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hours after dosing. |
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| Secondary | Ratio of BH2, B and BH4 Calculated From Total Biopterin Area Under the Curve (0-12hours) for Subjects Administered Sapropterin Dihydrochloride With Vitamin C to Subjects Administered Sapropterin Alone. | Ratio of Mean AUC (0-12 hours) for subjects receiving (Sapropterin dihydrochloride + Vitamin C)/ Mean AUC (0-12 hours) for subjects receiving Sapropterin dihydrochloride alone) for BH4, BH2, B, BH4/BH2 Ratio, and BH4 Calculated from Total Biopterin. | ITT population. AUC (0 to 12 hour) means were calculated for 44 subjects in the Sapropterin dihydrichloride and 43 subjects on Sapropterin dihydrochloride + Vitamin C | Posted | Mean | Standard Deviation | ratio | At 30 minutes prior to dosing, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hours after dosing. |
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| Secondary | Change From Baseline in Peripheral Arterial Tonometry (PAT) | PAT measures pulse wave amplitude of the small arteries of the finger as a surrogate to assess endothelial function and arterial stiffness using a finger plethysmographic probe and 5-minute occlusion of the brachial artery. Endothelial dysfunction, a protocol inclusion criteria, is defined by an abnormal PAT of < or = 1.70. Change is calculated as follows: end time measurement - starting time measurement. | ITT population. | Posted | Mean | Standard Deviation | Ratio | At Baseline, Day 13 and Day 27 |
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| Secondary | Change From Baseline in Systolic Blood Pressure (SBP) | Change is calculated as follows: end time measurement - starting time measurement. Mean daytime systolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) | ITT population | Posted | Mean | Standard Deviation | mm Hg | At Baseline, Day 13 and Day 27 |
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| Secondary | Change From Baseline in Diastolic Blood Pressure (DBP) | Change is calculated as follows: end time measurement - starting time measurement. Mean daytime diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) | ITT population | Posted | Mean | Standard Deviation | mm Hg | At Baseline, Day 13 and Day 27 |
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| Secondary | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. | ITT and Safety Population. Four subjects enrolled in the study before changing from a parallel to a cross over study not reflected in the data table in the Participant Flow module. Two subjects received sapropterin dihydrochloride only and two subjects received sapropterin dihydrichloride + vitamin C only. | Posted | Count of Participants | Participants | Up to 56 ± 3 Days. |
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| Secondary | Change From Baseline in Urinary 8-isoprostane/Creatinine | Biomarkers of endothelial function, oxidative stress, and inflammation as measured by 8-isoprostane. | ITT Population | Posted | Mean | Standard Deviation | pg/mg | At Baseline, Day 14 and Day 28 |
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| Secondary | Change From Baseline in Cyclic Guanosine Monophosphate (cGMP) | Biomarkers of endothelial function, oxidative stress, and inflammation as measured by cyclic guanosine monophosphate (cGMP). | ITT Population | Posted | Mean | Standard Deviation | pmol/mL | At Baseline, Day 14 and Day 28. |
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| Secondary | Change in Urinary Albumin to Creatinine Ratio (mg/g) | Change in Urinary Albumin to Creatinine Ratio (mg/g) from Baseline to Day 14, Baseline to Day 28, and from Day 14 to Day 28 | ITT Population | Posted | Mean | Standard Deviation | mg/g | Baseline, Day 14 and Day 28 |
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| Secondary | Number of Participants With Urinary Albumin to Creatinine Ratio <30 mg/g | Summary of Urinary Albumin to Creatinine Ratio (mg/g) by subjects with ratio <30 mg/g and subjects with ratios >=30 mg/g at Baseline, Day 14 and Day 28 | ITT Population | Posted | Count of Participants | Participants | Baseline, Day 14 and Day 28 |
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Up to 56 ± 3 Days.
Four subjects enrolled in the study before changing from a parallel to a cross over study and therefore are not reflected in the data table in the Participant Flow module. Two subjects received sapropterin dihydrochloride only and two subjects received sapropterin dihydrochloride + vitamin C only.
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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 | Sapropterin Dihydrochloride 10mg/kg | Sapropterin dihydrochloride 5 mg/kg twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14. The washout period of 1 day comprised between treatment regimens. | 0 | 49 | 0 | 49 | 19 | 49 |
| EG001 | Sapropterin Dihydrochloride 10mg/kg and Vitamin C | Sapropterin dihydrochloride 5 mg/kg + 500 mg vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14. The washout period of 1 day comprised between treatment regimens. | 0 | 50 | 0 | 50 | 16 | 50 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Stomach discomfort | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
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| Thirst | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Pharmaceutical product complaint | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Blood lactate dehydrogenase increased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Blood lactate dehydrogenase abnormal | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
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| Food poisoning | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Chest pain | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
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| Intertrigo candida | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joshua Lilienstein/Medical Director, Global Medical Affairs | BioMarin Pharmaceutical Inc. | 651.523.0310 | MEDINFO@bmrn.com |
| ID | Term |
|---|---|
| D010661 | Phenylketonurias |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C003402 | sapropterin |
| D001205 | Ascorbic Acid |
| ID | Term |
|---|---|
| D013400 | Sugar Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D006880 | Hydroxy Acids |
| D002241 | Carbohydrates |
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| Adverse Event |
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| withdrawal of consent |
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| Male |
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| ≥ 65 Years |
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| Black/African American |
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| Other |
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| Hispanic or Latino |
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