Trial · NCT00532844
A Phase 2, Pharmacokinetic (PK) Study of 6R-BH4 Alone or 6R-BH4 With Vitamin C in Subjects With Endothelial Dysfunction
NCT00532844, Phase 2, Completed, BioMarin Pharmaceutical; results first posted 2021-05-17
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Phase 2, Pharmacokinetic (PK) Study of 6R-BH4 Alone or 6R-BH4 With Vitamin C in Subjects With Endothelial Dysfunction. Trials, record NCT00532844. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00532844
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Phase 2, Pharmacokinetic (PK) Study of 6R-BH4 Alone or 6R-BH4 With Vitamin C in Subjects With Endothelial Dysfunction
- NCT number
- NCT00532844
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 52 participants, actual
- Lead sponsor
- BioMarin Pharmaceutical
- Conditions
- Endothelial Dysfunction
- Interventions
- Sapropterin Dihydrochloride, Sapropterin Dihydrochloride and Vitamin C
- First posted
- 2007-09-20
- Last updated
- 2021-05-17
- Results first posted
- 2021-05-17
Source ClinicalTrials.gov
Registered outcomes12
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Area Under the Curve (AUC0-12hrs) of Plasma BH4 Concentration | 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. | Plasma BH4 concentration area under the curve (AUC0-12 hrs) at the end of each regimen in subjects with endothelial dysfunction. |
| Secondary | Area Under the Curve (AUC0-12hrs) of Plasma BH2 and B Concentration | 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. | Plasma BH2 and B concentration area under the curve (AUC0-12hrs) at the end of each regimen in subjects with endothelial dysfunction. |
| Secondary | Area Under the Curve (AUC0-12hours) for Calculated BH4 (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. | 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. |
| 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. | 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 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. |
| Secondary | Change From Baseline in Peripheral Arterial Tonometry (PAT) | At Baseline, Day 13 and Day 27 | 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. |
| Secondary | Change From Baseline in Systolic Blood Pressure (SBP) | At Baseline, Day 13 and Day 27 | Change is calculated as follows: end time measurement - starting time measurement. Mean daytime systolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) |
| Secondary | Change From Baseline in Diastolic Blood Pressure (DBP) | At Baseline, Day 13 and Day 27 | Change is calculated as follows: end time measurement - starting time measurement. Mean daytime diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) |
| Secondary | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Up to 56 ± 3 Days. | 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. |
| Secondary | Change From Baseline in Urinary 8-isoprostane/Creatinine | At Baseline, Day 14 and Day 28 | Biomarkers of endothelial function, oxidative stress, and inflammation as measured by 8-isoprostane. |
| Secondary | Change From Baseline in Cyclic Guanosine Monophosphate (cGMP) | At Baseline, Day 14 and Day 28. | Biomarkers of endothelial function, oxidative stress, and inflammation as measured by cyclic guanosine monophosphate (cGMP). |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 registered outcomesOutcomes12
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Area Under the Curve (AUC0-12hrs) of Plasma BH4 Concentration | 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. | Intent-to-treat (ITT) Population | nM*hr | MEAN |
| SECONDARY | Area Under the Curve (AUC0-12hrs) of Plasma BH2 and B Concentration | 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. | ITT population | nM*hr | MEAN |
| SECONDARY | Area Under the Curve (AUC0-12hours) for Calculated BH4 (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. | ITT population | nM*hr | MEAN |
| 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. | 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. | 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 | ratio | MEAN |
| SECONDARY | Change From Baseline in Peripheral Arterial Tonometry (PAT) | At Baseline, Day 13 and Day 27 | ITT population. | Ratio | MEAN |
| SECONDARY | Change From Baseline in Systolic Blood Pressure (SBP) | At Baseline, Day 13 and Day 27 | ITT population | mm Hg | MEAN |
| SECONDARY | Change From Baseline in Diastolic Blood Pressure (DBP) | At Baseline, Day 13 and Day 27 | ITT population | mm Hg | MEAN |
| SECONDARY | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Up to 56 ± 3 Days. | 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. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Change From Baseline in Urinary 8-isoprostane/Creatinine | At Baseline, Day 14 and Day 28 | ITT Population | pg/mg | MEAN |
| SECONDARY | Change From Baseline in Cyclic Guanosine Monophosphate (cGMP) | At Baseline, Day 14 and Day 28. | ITT Population | pmol/mL | MEAN |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 outcomesResults by group75
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Area Under the Curve (AUC0-12hrs) of Plasma BH4 Concentration | Sapropterin Dihydrochloride 10 mg/kg | 633 | Standard Deviation 286 | nM*hr | |
| Area Under the Curve (AUC0-12hrs) of Plasma BH4 Concentration | Sapropterin Dihydrochloride+Vitamin C 10 mg/kg | 993 | Standard Deviation 545 | nM*hr | |
| Area Under the Curve (AUC0-12hrs) of Plasma BH2 and B Concentration | Sapropterin Dihydrochloride | BH2 | 875 | Standard Deviation 455 | nM*hr |
| Area Under the Curve (AUC0-12hrs) of Plasma BH2 and B Concentration | Sapropterin Dihydrochloride+Vitamin C | BH2 | 772 | Standard Deviation 376 | nM*hr |
| Area Under the Curve (AUC0-12hrs) of Plasma BH2 and B Concentration | Sapropterin Dihydrochloride | B | 231 | Standard Deviation 163 | nM*hr |
| Area Under the Curve (AUC0-12hrs) of Plasma BH2 and B Concentration | Sapropterin Dihydrochloride+Vitamin C | B | 185 | Standard Deviation 123 | nM*hr |
| Area Under the Curve (AUC0-12hours) for Calculated BH4 (From Total Biopterin) | Sapropterin Dihydrochloride | 440 | Standard Deviation 183 | nM*hr | |
| Area Under the Curve (AUC0-12hours) for Calculated BH4 (From Total Biopterin) | Sapropterin Dihydrochloride+Vitamin C | 440 | Standard Deviation 211 | nM*hr | |
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. | (Sapropterin Dihydrochloride+Vitamin C)/(Sapropterin Dihydrochloride) | BH2 | 0.998 | Standard Deviation 0.577 | ratio |
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. | (Sapropterin Dihydrochloride+Vitamin C)/(Sapropterin Dihydrochloride) | B | 1.04 | Standard Deviation 1.10 | ratio |
1 to 10 of 75Source ClinicalTrials.gov
See all 75 results by groupParticipant flow18
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Treatment Period - Day 1 to Day 14 | STARTED | Sapropterin Dihydrochloride 10mg/kg First; Then Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 24 | |
| Treatment Period - Day 1 to Day 14 | STARTED | Sapropterin Dihydrochloride 10mg/kg and Vitamin C First; Then Sapropterin Dihydrochloride 10mg/kg | 24 | |
| Treatment Period - Day 1 to Day 14 | COMPLETED | Sapropterin Dihydrochloride 10mg/kg First; Then Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 24 | |
| Treatment Period - Day 1 to Day 14 | COMPLETED | Sapropterin Dihydrochloride 10mg/kg and Vitamin C First; Then Sapropterin Dihydrochloride 10mg/kg | 23 | |
| Treatment Period - Day 1 to Day 14 | NOT COMPLETED | Sapropterin Dihydrochloride 10mg/kg First; Then Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 0 | |
| Treatment Period - Day 1 to Day 14 | NOT COMPLETED | Sapropterin Dihydrochloride 10mg/kg and Vitamin C First; Then Sapropterin Dihydrochloride 10mg/kg | 1 | |
| Washout (1 Day) | STARTED | Sapropterin Dihydrochloride 10mg/kg First; Then Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 24 | |
| Washout (1 Day) | STARTED | Sapropterin Dihydrochloride 10mg/kg and Vitamin C First; Then Sapropterin Dihydrochloride 10mg/kg | 23 | |
| Washout (1 Day) | COMPLETED | Sapropterin Dihydrochloride 10mg/kg First; Then Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 24 | |
| Washout (1 Day) | COMPLETED | Sapropterin Dihydrochloride 10mg/kg and Vitamin C First; Then Sapropterin Dihydrochloride 10mg/kg | 23 |
1 to 10 of 18Source ClinicalTrials.gov
See all 18 participant flowAdverse events58
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Diarrhoea | Gastrointestinal disorders | Sapropterin Dihydrochloride 10mg/kg | 5 | 49 | |
| other | Diarrhoea | Gastrointestinal disorders | Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 5 | 50 | |
| other | Stomach discomfort | Gastrointestinal disorders | Sapropterin Dihydrochloride 10mg/kg | 2 | 49 | |
| other | Stomach discomfort | Gastrointestinal disorders | Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 2 | 50 | |
| other | Vomiting | Gastrointestinal disorders | Sapropterin Dihydrochloride 10mg/kg | 0 | 49 | |
| other | Vomiting | Gastrointestinal disorders | Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 2 | 50 | |
| other | Constipation | Gastrointestinal disorders | Sapropterin Dihydrochloride 10mg/kg | 1 | 49 | |
| other | Constipation | Gastrointestinal disorders | Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 1 | 50 | |
| other | Dry mouth | Gastrointestinal disorders | Sapropterin Dihydrochloride 10mg/kg | 0 | 49 | |
| other | Dry mouth | Gastrointestinal disorders | Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 1 | 50 |
1 to 10 of 58Source ClinicalTrials.gov
See all 58 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Sapropterin Dihydrochloride 10mg/kg | 0 | 49 |
| Total, all-cause mortality | Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 0 | 50 |
| Total, other adverse events | Sapropterin Dihydrochloride 10mg/kg | 19 | 49 |
| Total, other adverse events | Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 16 | 50 |
| Total, serious adverse events | Sapropterin Dihydrochloride 10mg/kg | 0 | 49 |
| Total, serious adverse events | Sapropterin Dihydrochloride 10mg/kg and Vitamin C | 0 | 50 |
Source ClinicalTrials.gov
Papers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons2
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Sapropterin Dihydrochloride 10mg/kg vs Sapropterin Dihydrochloride 10mg/kg and Vitamin C: deaths from any cause | Trial comparisons |
| Sapropterin Dihydrochloride 10mg/kg vs Sapropterin Dihydrochloride 10mg/kg and Vitamin C: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT00532844
GET https://conductscience.org/api/trials/v1/NCT00532844/results?page=2