NCT00325962

Brief Summary

The purpose of this study is to determine whether 6R-BH4 (sapropterin dihydrochloride) is safe and effective in the treatment of poorly controlled hypertension in the presence or absence of type 2 diabetes.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
84

participants targeted

Target at P25-P50 for phase_2 hypertension

Timeline
Completed

Started May 2006

Typical duration for phase_2 hypertension

Geographic Reach
1 country

24 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2006

Completed
10 days until next milestone

First Submitted

Initial submission to the registry

May 11, 2006

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 15, 2006

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2006

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2008

Completed
Last Updated

July 21, 2009

Status Verified

July 1, 2009

Enrollment Period

7 months

First QC Date

May 11, 2006

Last Update Submit

July 17, 2009

Conditions

Keywords

HypertensionType 2 Diabetes6R-BH4BH4BH4 deficiencysapropterin dihydrochlorideendothelial dysfunctionNONitric Oxide

Outcome Measures

Primary Outcomes (1)

  • To compare oral 6R-BH4 to placebo with respect to change from baseline in arterial systolic blood pressure after 8 weeks of treatment in subjects with poorly controlled hypertension.

Secondary Outcomes (4)

  • To compare oral 6R-BH4 to placebo with respect to change from baseline in arterial diastolic blood pressure after 8 weeks of treatment in subjects with poorly controlled hypertension

  • To compare oral 6R-BH4 to placebo with respect to change from baseline in insulin sensitivity after 8 weeks of treatment in subjects with both type 2 diabetes and poorly controlled hypertension

  • To compare oral 6R-BH4 to placebo with respect to change from baseline in eNOS activity and endothelial dysfunction after 8 weeks of treatment in subjects with poorly controlled hypertension

  • To assess the safety of oral dosing of 6R-BH4 in subjects with poorly controlled hypertension

Interventions

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • At least 18 years of age.
  • Willing and able to comply with all study-related procedures.
  • History of documented essential hypertension (BP greater than or equal to 140 mm Hg systolic and/or 90 mm Hg diastolic measured on 2 separate occasions).
  • Have poorly controlled hypertension despite use of at least two conventional antihypertensive agents with different mechanisms of action taken concurrently and consistently for at least 3 months before randomization. (Note: Antihypertensive agents may be individual or combined into a single medication.)
  • During the two-week screening period, mean SBP and mean DBP fall within the following ranges:
  • Mean SBP between 135 and 160 mm Hg
  • Mean DBP between 85 and 110 mm Hg
  • 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 this study.
  • Individuals in the diabetic cohort must meet this additional criterion:
  • Documented history of type 2 diabetes that has been treated using the same therapy for at least 3 months.

You may not qualify if:

  • Previous treatment with any formulation of BH4.
  • Known allergy or hypersensitivity to any excipient of 6R-BH4.
  • Known secondary cause for hypertension.
  • Concurrent disease or condition that would interfere with study participation or safety such as bleeding disorders, history of syncope or vertigo, severe gastrointestinal reflux disease (GERD), symptomatic coronary or peripheral vascular disease, arrhythmia, organ transplant, organ failure, or type 1 diabetes mellitus.
  • Any sever co-morbid condition that would limit life expectancy to less than 6 months.
  • Serum creatinine \>2.0mg/dL or hepatic enzyme levels more than 2 times the upper limit of normal.
  • Requirement for concomitant treatment with any drug known to inhibit folate metabolism (e.g., methotrexate).
  • Concomitant treatment with levodopa.
  • Concomitant treatment with any phosphodiesterase (PDE) 5 inhibitor (e.g., Viagra(R), Cialis(R), or Levitra(R), or Revatio (TM) or any PDE 3 inhibitor (e.g., cilostazol, milrinone, or vesnarinone).)
  • Use of any investigational product or device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
  • Pregnant or breastfeeding at screening or planning to become pregnant (subject or partner) at any time during study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

Unknown Facility

Hoover, Alabama, United States

Location

Unknown Facility

Huntsville, Alabama, United States

Location

Unknown Facility

Mobile, Alabama, United States

Location

Unknown Facility

Muscle Shoals, Alabama, United States

Location

Unknown Facility

Gilbert, Arizona, United States

Location

Unknown Facility

Phoenix, Arizona, United States

Location

Unknown Facility

Anaheim, California, United States

Location

Unknown Facility

Burbank, California, United States

Location

Unknown Facility

Cudahy, California, United States

Location

Unknown Facility

Long Beach, California, United States

Location

Unknown Facility

Roseville, California, United States

Location

Unknown Facility

San Francisco, California, United States

Location

Unknown Facility

Denver, Colorado, United States

Location

Unknown Facility

Pembroke Pines, Florida, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Decatur, Georgia, United States

Location

Unknown Facility

Indianapolis, Indiana, United States

Location

Unknown Facility

Auburn, Maine, United States

Location

Unknown Facility

Scarborough, Maine, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

Charlotte, North Carolina, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Knoxville, Tennessee, United States

Location

Unknown Facility

Carrollton, Texas, United States

Location

Related Links

MeSH Terms

Conditions

HypertensionDiabetes Mellitus, Type 2Phenylketonurias

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular DiseasesDiabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesBrain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesAmino Acid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

  • Martha Nicholson, MD

    BioMarin Pharmaceutical

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

May 11, 2006

First Posted

May 15, 2006

Study Start

May 1, 2006

Primary Completion

December 1, 2006

Study Completion

December 1, 2008

Last Updated

July 21, 2009

Record last verified: 2009-07

Locations