Status:

COMPLETED

6R-BH4 Pulmonary Arterial Hypertension Study

Lead Sponsor:

Vanderbilt University

Collaborating Sponsors:

National Institutes of Health (NIH)

BioMarin Pharmaceutical

Conditions:

Pulmonary Arterial Hypertension

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

The purpose of this study is to determine whether the addition of sapropterin dihydrochloride (6R-BH4) to existing treatment has any effect in patients with pulmonary arterial hypertension (PAH). Pati...

Detailed Description

The primary objective of the study is to evaluate the safety of oral 6R-BH4, administered in escalating doses in addition to standard care, in subjects with pulmonary arterial hypertension (PAH). The...

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

March 1 2008

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

October 1 2008

Estimated Enrollment :

14 Patients enrolled

Trial Details

Trial ID

NCT00435331

Start Date

March 1 2008

End Date

October 1 2008

Last Update

June 19 2013

Active Locations (1)

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Vanderbilt Medical Center

Nashville, Tennessee, United States, 37232