Intermittent ClaudicationPhase 2NCT00403494

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

A Phase 2 study testing Sapropterin Dihydrochloride in people with Intermittent Claudication, run by BioMarin Pharmaceutical at 20 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 40 to 80 years
Conditions the study is for: Intermittent Claudication
What is being tested?: Sapropterin Dihydrochloride
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 190 participants
Where: 20 sitesin 2 countries
Study dates: Dec 2006to Jan 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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

Who cannot join

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)

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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

Trial locations and contacts

20 sites in 2 countries.

Country

City, postcode or hospital

20 sites in 2 countries

United States17 sites

Study site
Auburn, Maine
Study site
Charlotte, North Carolina
Study site
Clearwater, Florida
Study site
Conyers, Georgia
Study site
Dallas, Texas
Study site
Indianapolis, Indiana
Study site
Jacksonville, Florida
Study site
Knoxville, Tennessee
Study site
Norfolk, Virginia
Study site
Portland, Oregon
Study site
Richmond, Virginia
Study site
Sacramento, California
Study site
San Antonio, Texas
Study site
San Diego, California
Study site
Santa Ana, California
Study site
Santa Rosa, California
Study site
Scottsdale, Arizona, 85054

Other trials in United States

Argentina3 sites

Study site
Buenos Aires
Study site
Corrientes
Study site
Santa Fe

Other trials in Argentina

About this study

Official title: A Phase 2, Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled, Parallel Study of the Effects of Sapropterin Dihydrochloride on Symptomatic Peripheral Arterial Disease

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).

Read the 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
Being tested: Placebo, Sapropterin Dihydrochloride
Keywords: Intermittent Claudication, IC, Symptomatic Peripheral Arterial Disease, Peripheral Arterial Disease, PAD, 6R-BH4, BH4, sapropterin dihydrochloride, endothelial dysfunction, Nitric Oxide, NO
Medical subject headings: Intermittent Claudication, Peripheral Arterial Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboOther
Subjects receive matching oral Placebo twice daily for 24 weeks.
Sapropterin DihydrochlorideDrug
Subjects receive 400 mg oral sapropterin dihydrochloride twice daily for 24 weeks.

Study groups in NCT00403494
Study group	Role	What they receive
Sapropterin dihydrochloride	Experimental	Subjects receive 400 mg oral sapropterin dihydrochloride twice daily for 24 weeks. Receives: Drug: Sapropterin Dihydrochloride
Placebo	Placebo comparator	Subjects receive matching oral Placebo twice daily for 24 weeks. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.
Measured: Up to 24-weeks

Secondary outcomes (1)

Change in Claudication Onset Time (COT) From Baseline
Time, in minutes, when the subject first begins to experience claudication symptoms, regardless of whether this is manifested as muscle pain, ache, cramp, numbness or fatigue.
Measured: Baseline and up to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2006Jan 2009

First posted23 Nov 2006 (estimated)
Study startDec 2006
Primary completionNov 2008
Study completionJan 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Intermittent ClaudicationStudies of the same condition, open and under way.
More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 190 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00403494
Sponsor's protocol ID: PAD-001
Status last verified: Dec 2020
First submitted: 21 Nov 2006
Last updated: 7 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
EVERO Drug-coated Balloon (DCB) Randomized Trial
Peripheral Vascular Disease, Peripheral Arterial Disease
Recruiting
Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease
Peripheral Arterial Disease, Intermittent Claudication
Active, not recruitingPhase 4
Ramipril Treatment of Claudication: Oxidative Damage and Muscle Fibrosis
Peripheral Arterial Disease
RecruitingPhase 3
Improving Mobility After Revascularization in Peripheral Artery Disease
Peripheral Artery Disease, Intermittent Claudication

All Intermittent Claudication trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled, Parallel Study of the Effects of Sapropterin Dihydrochloride on Symptomatic Peripheral Arterial Disease
ClinicalTrials.gov ID: NCT00403494
Acronym / sponsor ID: PAD-001
Conditions: Intermittent Claudication
Keywords: Intermittent Claudication, IC, Symptomatic Peripheral Arterial Disease, Peripheral Arterial Disease, PAD, 6R-BH4, BH4, sapropterin dihydrochloride
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 190 participants (actual)
Lead sponsor: BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
Study start: Dec 2006
Primary completion: Nov 2008 (actual)
Study completion: Jan 2009 (actual)
First posted: 23 Nov 2006 (estimated)
Results: Posted 7 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Sapropterin dihydrochloride	Experimental	Drug: Sapropterin DihydrochlorideSubjects receive 400 mg oral sapropterin dihydrochloride twice daily for 24 weeks.
Placebo	Placebo comparator	Other: PlaceboSubjects receive matching oral Placebo twice daily for 24 weeks.

Who may qualify

Ages: 40 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

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:
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%

Key exclusion criteria (19 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboSubjects receive matching oral Placebo twice daily for 24 weeks.	Other	Placebo
Sapropterin DihydrochlorideSubjects receive 400 mg oral sapropterin dihydrochloride twice daily for 24 weeks.	Drug	Sapropterin dihydrochloride

Primary outcome

Change in Peak Walking Time (PWT) From Baseline
Time frame: Baseline and up to Week 24
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).
Number of Subjects With Adverse Events (AEs)
Time frame: Up to 24-weeks
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.

1 secondary outcome

Change in Claudication Onset Time (COT) From Baseline
Time frame: Baseline and up to Week 24

Results and safety

Results posted to the registry on 7 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sapropterin Dihydrochloride	96	81
Placebo	94	80

Primary outcome: Change in Peak Walking Time (PWT) From Baseline

Time frame: Baseline and up to Week 24. Mean (Standard Deviation). Unit: minutes

Measure	Sapropterin Dihydrochloride n = 87	Placebo n = 83
Baseline	5.394 (2.803)	5.712 (2.876)
Change from Baseline to Week 24	1.121 (2.775)	1.493 (2.597)

Sapropterin Dihydrochloride vs Placebo: Mean Difference (Final Values): -0.021 (95% CI -0.138 to 0.097), p = 0.727, t-test, 2 sided

Population analysed: Intent-To-Treat Population consisting of all subjects who were randomized, received 1 dose of study drug and had at least 1 post-baselline treadmill test.

Primary outcome: Number of Subjects With Adverse Events (AEs)

Time frame: Up to 24-weeks. Count of participants. Unit: Participants

Measure	Sapropterin Dihydrochloride n = 97	Placebo n = 91
Any AEs	84	66
Study Drug-related AEs	29	30
Any SAEs	14	11
Study-Drug-related SAEs	0	1
Any AEs leading to Study Withdrawal	11	7
Study Drug-related AEs leading to Study WIthdrawal	4	5
Any SAEs Leading to Study Withdrawal	4	1
Study Drug-related SAEs Leading to Study Withdrawal	0	1

Population analysed: Of the 188 patients (96 randomized to study drug and 94 to placebo.) 2 subjects randomized to receive placebo, received at least 1 dose of study drug and were included in the study drug group. 1 participant from each group was excluded from the safety analysis because they did not have at least 1 post-Baseline safety assessment.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to 25 Weeks. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sapropterin Dihydrochloride	14 of 97 (14.4%)	84 of 97 (86.6%)	1 of 97
Placebo	11 of 91 (12.1%)	66 of 91 (72.5%)	0 of 91

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
BioMarin Pharmaceutical Inc. websiteLink provided by the sponsor.

Related trials for Intermittent Claudication

Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
EVERO Drug-coated Balloon (DCB) Randomized Trial
Peripheral Vascular Disease, Peripheral Arterial Disease
Recruiting
Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease
Peripheral Arterial Disease, Intermittent Claudication
Active, not recruitingPhase 4
Ramipril Treatment of Claudication: Oxidative Damage and Muscle Fibrosis
Peripheral Arterial Disease
RecruitingPhase 3
Improving Mobility After Revascularization in Peripheral Artery Disease
Peripheral Artery Disease, Intermittent Claudication

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Don Nwose, MD study director

BioMarin Pharmaceutical

20 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sapropterin Dihydrochloride in people with Intermittent Claudication, run by BioMarin Pharmaceutical at 20 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Peak Walking Time (PWT) From Baseline (time frame: Baseline and up to Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00403494.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2021.