6R-BH4 Pulmonary Arterial Hypertension Study

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00435331
• Date of registration: 12/02/2007
• Prospective Registration: Yes
• Primary sponsor: Vanderbilt University
• Public title: 6R-BH4 Pulmonary Arterial Hypertension Study
• Scientific title: A Phase 1, Multicenter, Open-label, Dose-escalation Study to Evaluate the Safety and Efficacy of 6R-BH4 in Subjects With Pulmonary Arterial Hypertension
• Date of first enrolment: March 2008
• Target sample size: 14
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00435331
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Ivan M. Robbins, MD
• Affiliation: Vanderbilt University

Key inclusion & exclusion criteria

Inclusion Criteria:

- Documented diagnosis of PAH, defined as mean pulmonary arterial pressure > 25 mm Hg
(measured by catheter).

- PAH is primary (idiopathic) or is secondary and caused by collagen vascular disease,
congenital heart disease, or thromboembolic disease.

- Modified New York Heart Association (NYHA) classification I, II, or III that has been
stable for at least 8 weeks prior to enrollment.

- 6MW distance, as performed at screening or within three months (12 weeks) prior to
screening, of = 200 and = 500 meters.

- Receiving stable doses of one or more medications that are approved for treatment of
PAH, except for any agents specifically prohibited by this protocol, for a minimum of
12 consecutive weeks before enrollment. Note: anticoagulant therapy can be adjusted
according to target INR.

- Receiving stable doses of concomitant medication for other conditions, except agents
specifically prohibited by the protocol.

- At least 18 years of age and willing and able to complete an informed consent form.

- 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.

Exclusion Criteria:

- Previous treatment with any formulation of BH4.

- Known allergy or hypersensitivity to any excipient of 6R BH4.

- History of systemic hypotension, defined as systolic BP < 100 mm Hg and/or diastolic
BP < 60 mm Hg.

- Treatment at screening or perceived need for treatment during the course of the study
with any of the following:

- intravenous epoprostenol

- inhaled iloprost

- subcutaneous treprostinil

- levodopa

- any PDE 3 inhibitor, such as cilostazol or milrinone

- any drug known to inhibit folate metabolism, such as methotrexate (eg,
TrexallR), tomizine, trimethoprim, sulfanilamide, deoxycoformycin

- nitrates

- Diet supplementation with L-arginine or L-citrulline within 30 days of enrollment.

- Diet supplementation with high doses (> 3 times the recommended daily allowance) of
antioxidants, such as Vitamin C.

- Use of any investigational product or device within 30 days prior to screening, or
known requirement for any investigational agent prior to completion of all scheduled
study assessments.

- Known to be positive for human immunodeficiency virus (HIV).

- An additional medical condition, serious intercurrent illness, or other extenuating
circumstance that, in the opinion of the investigator, may significantly interfere
with study compliance, including all prescribed evaluations and follow-up activities.
Concurrent disease or condition that may interfere with study participation or safety
include bleeding disorders, arrhythmia, organ transplant (other than lung), organ
failure, current neoplasm, poorly controlled diabetes mellitus, and serious
neurological disorders.

- Serum creatinine > 2.0 mg/dL (180 µM/L) or hepatic enzyme levels more than 2 times
the upper limit of normal.

- Pregnant or lactating at screening, or planning to become pregnant (self or partner)
at any time during study.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: sapropterin dihydrochloride (6R-BH4)

Primary Outcome(s)

To evaluate the safety of oral 6R-BH4, administered in escalating doses in addition to standard care, in subjects with pulmonary arterial hypertension (PAH). [Time Frame: Up to 14 weeks]

Secondary Outcome(s)

Change in biochemical markers of endothelial dysfunction and nitric oxide synthetase activity (coupled and uncoupled). [Time Frame: Up to 14 weeks]

Change in biomarkers of disease progression, 6-minute walk (6MW) distance, Borg dyspnea scores, and quality of life (QOL) measures. [Time Frame: Up to 14 weeks]

Secondary ID(s)

WILK1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

BioMarin Pharmaceutical

National Institutes of Health (NIH)