A Phase 2 Study of the Effects of Sapropterin Dihydrochloride on Symptomatic Peripheral Arterial Disease

NCT ID: NCT00403494

Last Updated: 2021-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2009-01-31

Brief Summary

The purpose of this study is to evaluate whether sapropterin dihydrochloride is safe and effective in the treatment of intermittent claudication (IC) caused by peripheral arterial disease (PAD).

Detailed Description

This was a Phase 2, multicenter, multinational, prospective, randomized, double-blind, placebo-controlled, parallel study designed to assess the efficacy and safety of sapropterin dihydrochloride in subjects with intermittent claudication (IC) caused by peripheral arterial disease (PAD). Subjects who met initial screening criteria were monitored criteria and that dosages of permitted concomitant medications were stable.

Conditions

Intermittent Claudication

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Sapropterin dihydrochloride

Subjects receive 400 mg oral sapropterin dihydrochloride twice daily for 24 weeks.

Group Type: EXPERIMENTAL

Sapropterin Dihydrochloride

Intervention Type: DRUG

Subjects receive 400 mg oral sapropterin dihydrochloride twice daily for 24 weeks.

Placebo

Subjects receive matching oral Placebo twice daily for 24 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Subjects receive matching oral Placebo twice daily for 24 weeks.

Interventions

Placebo

Subjects receive matching oral Placebo twice daily for 24 weeks.

Intervention Type: OTHER

Sapropterin Dihydrochloride

Subjects receive 400 mg oral sapropterin dihydrochloride twice daily for 24 weeks.

Intervention Type: DRUG

Eligibility 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 ankle-brachial index (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, peak walking time (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 Heart Bar
• 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Don Nwose, MD

Role: STUDY_DIRECTOR

BioMarin Pharmaceutical

Locations

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

Buenos Aires, , Argentina

Corrientes, , Argentina

Santa Fe, , Argentina

Countries

United States; Argentina

Related Links

http://www.bmrn.com

BioMarin Pharmaceutical Inc. website

Other Identifiers

PAD-001

Identifier Type: -

Identifier Source: org_study_id