A Phase 2 Study of the Effects of 6R-BH4 on Symptomatic Peripheral Arterial Disease
Information source: BioMarin Pharmaceutical
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Intermittent Claudication
Intervention: Placebo for 6R-BH4 (sapropterin dihydrochloride) (Drug); 6R-BH4 (sapropterin dihydrochloride) (Drug); 6R-BH4 (sapropterin dihydrochloride) (Drug); Placebo for 6R-BH4 (sapropterin dihydrochloride) (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: BioMarin Pharmaceutical Official(s) and/or principal investigator(s): Don Nwose, MD, Study Director, Affiliation: BioMarin Pharmaceutical
Summary
The purpose of this study is to evaluate whether 6R-BH4 (sapropterin dihydrochloride) is
safe and effective in the treatment of intermittent claudication (IC) caused by peripheral
arterial disease (PAD).
Clinical Details
Official title: A Phase 2, Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled, Parallel Study of the Effects of 6R-BH4 on Symptomatic Peripheral Arterial Disease
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: To compare oral 6R-BH4 to placebo with respect to change from Baseline to Week 24 in peak walking time (PWT)
Secondary outcome: To compare oral 6R-BH4 to placebo with respect to change from Baseline to Week 24 in claudication onset time (COT)Tertiary Outcome: To compare oral 6R-BH4 to placebo with respect to change from Baseline to Weeks 12 and 24 in functional status as measured by the Walking Impairment Questionnaire (WIQ) and Medical Outcomes Scale Short Form (MOS SF-36) Tertiary Outcome: To compare oral 6R-BH4 to placebo with respect to change from Baseline to Weeks 12 and 24 in mean systolic blood pressure (BP) (seated, rested) and mean diastolic BP (seated, rested) Tertiary Outcome: To compare oral 6R-BH4 to placebo with respect to change from Baseline to Weeks 12 and 24 in ankle-brachial index (ABI) or toe-brachial index (TBI) Tertiary Outcome: To compare oral 6R-BH4 to placebo with respect to change from Baseline to Weeks 12 & 24 in International Index of Erectile Function (IIEF; short form) or the Female Sexual Function Index (FSFI),if available in subject's primary language Tertiary Outcome: To compare oral 6R-BH4 to placebo with respect to change from Baseline to Weeks 12 and 24 in insulin sensitivity Tertiary Outcome: To compare oral 6R-BH4 to placebo with respect to change from Baseline to Weeks 12 and 24 in biomarkers of eNOS activity and oxidative stress as measured by cGMP and 8-isoprostane, respectively Tertiary Outcome: To compare oral 6R-BH4 to placebo with respect to change from Baseline to Weeks 12 and 24 in endothelial function as measured by peripheral arterial tonometry (PAT) Safety Objective: To assess the safety of oral dosing of 6R-BH4 Tertiary Outcome: To compare oral 6R-BH4 to placebo with respect to change from Baseline to Week 12 in PWT and COT
Eligibility
Minimum age: 40 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- At least 40 years and no more than 80 years old
- A 6-month (or longer) history of walking limitation because of IC, severity of which
has not changed in the past 3 months
- Diagnosis of PAD secondary to atherosclerosis, with PAD documented at Screening by
one of the following criteria:
1. Resting ABI < 0. 9 in at least one leg
2. If resting ABI is 0. 9-1. 0, minimum post-exercise drop in ABI of at least 25% in
at least one leg
3. If resting ABI is > 1. 3 (indicating non-compressible vessels), vascular etiology
documented by toe-brachial index (TBI) < 0. 7 in at least one leg
- On Gardner graded treadmill protocol, PWT of at least 1 minute, but no more than 12
minutes
- Variation in PWT between two consecutive screening treadmill tests less than or equal
to 25%
- If currently receiving treatment with or taking any of the following, willing and
able to discontinue for 30 days before Screening and throughout the entire study
(including the follow-up period): phosphodiesterase (PDE) 5 inhibitor (eg, Viagra®,
Cialis®, Levitra®, or Revatio™), any PDE 3 inhibitor (eg, cilostazol, milrinone, or
vesnarinone), pentoxifylline (Trental®), nitrates, L-arginine, ginkgo biloba, or
HeartBar
- For the approximately 50% of subjects enrolled to receive vitamin C with study drug
or placebo, subjects must be willing to discontinue taking vitamin C supplements or a
multivitamin containing vitamin C during study.
- Antihypertensive therapy, cholesterol-lowering therapy (eg, statins), and diabetic
therapy (if applicable) has been stable for 30 days prior to Screening.
- Has not changed smoking or exercise habits in 30 days prior to randomization and is
unlikely to do so during the study period
- 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
- Willing and able to comply with all study-related procedures
- 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:
- Critical leg ischemia, manifested by pain at rest, ulceration, gangrene, or leg
amputation
- Surgical intervention to alleviate symptoms of claudication (eg, vascular
reconstruction, sympathectomy) within 6 months or any endovascular interventions or
cardiovascular surgery within 3 months
- Walking limited by reasons other than claudication (eg, arthritis, lung disease,
exercise-limiting cardiac disease, or skin or foot lesions that limit walking)
- Clinically significant ECG change during or after exercise treadmill test at
Screening or Baseline visit(s)
- Myocardial infarction, deep vein thrombosis, or cerebrovascular infarct within 3
months of Screening
- Body mass index > 40 (gross obesity)
- Hypertension at Screening, defined as seated mean resting BP value of > 160 mmHg
systolic, > 110 mmHg diastolic, or both
- Hypotension at Screening, defined as seated mean resting BP values of < 100 mmHg
systolic or < 55 mmHg diastolic, or as clinically significant symptomatic
(orthostatic) hypotension
- Non-atherosclerotic vascular disease (eg, Buerger's disease or popliteal entrapment
syndrome)
- Previous treatment with any formulation of BH4
- Known allergy or hypersensitivity to any excipient of 6R-BH4
- Concurrent disease or condition that would interfere with study participation or
safety such as bleeding disorders, history of severe gastrointestinal reflux disease,
arrhythmia, organ transplant, organ failure, current neoplasm, type 1 diabetes
mellitus, or serious neurological disorders (including seizures)
- Previous treatment with gene therapy or other vascular endothelial growth factor
(VEGF)-related treatment
- Any severe co-morbid condition that would limit life expectancy to less than 6 months
- Serum creatinine > 2. 0 mg/dL or hepatic enzyme levels more than 2 times the upper
limit of normal
- Concomitant treatment with levodopa
- Requirement for concomitant treatment with any drug known to inhibit folate
metabolism (eg, methotrexate)
- 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 the study
Locations and Contacts
Buenos Aires, Argentina
Corrientes, Argentina
Santa Fe, Argentina
Scottsdale, Arizona, United States
Sacramento, California, United States
San Diego, California, United States
Santa Ana, California, United States
Santa Rosa, California, United States
Clearwater, Florida, United States
Jacksonville, Florida, United States
Conyers, Georgia, United States
Indianapolis, Indiana, United States
Auburn, Maine, United States
Charlotte, North Carolina, United States
Portland, Oregon, United States
Knoxville, Tennessee, United States
Dallas, Texas, United States
San Antonio, Texas, United States
Norfolk, Virginia, United States
Richmond, Virginia, United States
Additional Information
BioMarin Pharmaceutical Inc. website
Starting date: December 2006
Last updated: September 4, 2014
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