NCT00403494

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).

Trial Health

90
On Track

Trial Health Score

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

Enrollment
190

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Dec 2006

Geographic Reach
2 countries

20 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

First Submitted

Initial submission to the registry

November 21, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 23, 2006

Completed
8 days until next milestone

Study Start

First participant enrolled

December 1, 2006

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2008

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2009

Completed
12 years until next milestone

Results Posted

Study results publicly available

January 7, 2021

Completed
Last Updated

January 7, 2021

Status Verified

December 1, 2020

Enrollment Period

1.9 years

First QC Date

November 21, 2006

Results QC Date

October 30, 2020

Last Update Submit

December 14, 2020

Conditions

Intermittent Claudication

Keywords

Intermittent ClaudicationICSymptomatic Peripheral Arterial DiseasePeripheral Arterial DiseasePAD6R-BH4BH4sapropterin dihydrochlorideendothelial dysfunctionNitric OxideNO

Outcome Measures

Primary Outcomes (2)

  • Change in Peak Walking Time (PWT) From Baseline

    This is to assess the effect of oral sapropterin dihydrochloride versus placebo on peak walking time (PWT) in subjects with intermittent claudication (IC) caused by peripheral arterial disease (PAD).

    Baseline and up to Week 24

  • Number of Subjects With Adverse Events (AEs)

    Adverse events were described and summarized with focus on treatment- emergent events (TEAEs). A TEAE was defined as any AE that presented , increased in frequency or worsened in severity following initiation of study drug administration. If the onset of an AE was missing then the AE was considered treatment emergent. Drug-related AEs are AEs classified by the investigator as possibly or probably related to study drug.

    Up to 24-weeks

Secondary Outcomes (1)

  • Change in Claudication Onset Time (COT) From Baseline

    Baseline and up to Week 24

Other Outcomes (1)

  • Change in Peak Walking Time From Baseline With and Without Vitamin C

    Baseline up to 24 weeks

Study Arms (2)

Sapropterin dihydrochloride

EXPERIMENTAL

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

Drug: Sapropterin Dihydrochloride

Placebo

PLACEBO COMPARATOR

Subjects receive matching oral Placebo twice daily for 24 weeks.

Other: Placebo

Interventions

PlaceboOTHER

Subjects receive matching oral Placebo twice daily for 24 weeks.

Placebo
Sapropterin DihydrochlorideDRUG

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

Sapropterin dihydrochloride

Eligibility Criteria

Age40 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • Resting ankle-brachial index (ABI) \< 0.9 in at least one leg
  • If resting ABI is 0.9-1.0, minimum post-exercise drop in ABI of at least 25% in at least one leg
  • 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
  • +1 more criteria

You may not qualify if:

  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

Unknown Facility

Scottsdale, Arizona, 85054, United States

Location

Unknown Facility

Sacramento, California, United States

Location

Unknown Facility

San Diego, California, United States

Location

Unknown Facility

Santa Ana, California, United States

Location

Unknown Facility

Santa Rosa, California, United States

Location

Unknown Facility

Clearwater, Florida, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Conyers, Georgia, United States

Location

Unknown Facility

Indianapolis, Indiana, United States

Location

Unknown Facility

Auburn, Maine, United States

Location

Unknown Facility

Charlotte, North Carolina, United States

Location

Unknown Facility

Portland, Oregon, United States

Location

Unknown Facility

Knoxville, Tennessee, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Norfolk, Virginia, United States

Location

Unknown Facility

Richmond, Virginia, United States

Location

Unknown Facility

Buenos Aires, Argentina

Location

Unknown Facility

Corrientes, Argentina

Location

Unknown Facility

Santa Fe, Argentina

Location

Related Links

MeSH Terms

Conditions

Intermittent ClaudicationPeripheral Arterial Disease

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Peripheral Vascular DiseasesVascular DiseasesCardiovascular DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsAtherosclerosisArteriosclerosisArterial Occlusive Diseases

Results Point of Contact

Title
Joshua Lilienstein/Medical Director, Global Medical Affairs
Organization
BioMarin Pharmaceutical Inc.
MEDINFO@bmrn.com
651.523.0310

Study Officials

  • Don Nwose, MD

    BioMarin Pharmaceutical

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 21, 2006

First Posted

November 23, 2006

Study Start

December 1, 2006

Primary Completion

November 1, 2008

Study Completion

January 1, 2009

Last Updated

January 7, 2021

Results First Posted

January 7, 2021

Record last verified: 2020-12

Locations

AR(3)US(17)