Clinical trial NCT00325962: A Study of the Effects of 6R-BH4 on Blood Pressure in Subjects With Poorly Controlled Systemic Hypertension
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Study of the Effects of 6R-BH4 on Blood Pressure in Subjects With Poorly Controlled Systemic Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: Hypertension
Type 2 Diabetes
6R-BH4
BH4
BH4 deficiency
sapropterin dihydrochloride
endothelial dysfunction
NO
Nitric Oxide
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2006-05-15
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.
* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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:
measure: 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
measure: 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
measure: 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
measure: To assess the safety of oral dosing of 6R-BH4 in subjects with poorly controlled hypertension
Other outcomes:
Locations:
city: Hoover
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Muscle Shoals
country: United States
state: Alabama
city: Gilbert
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Anaheim
country: United States
state: California
city: Burbank
country: United States
state: California
city: Cudahy
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Roseville
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Pembroke Pines
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Auburn
country: United States
state: Maine
city: Scarborough
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
city: Charlotte
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Knoxville
country: United States
state: Tennessee
city: Carrollton
country: United States
state: Texas
Study officials:
affiliation: BioMarin Pharmaceutical
name: Martha Nicholson, MD
role: STUDY_DIRECTOR
References: