- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00403494
A Phase 2 Study of the Effects of Sapropterin Dihydrochloride on Symptomatic Peripheral Arterial Disease
14 dicembre 2020 aggiornato da: BioMarin Pharmaceutical
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).
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
190
Fase
- Fase 2
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Buenos Aires, Argentina
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Corrientes, Argentina
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Santa Fe, Argentina
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Arizona
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Scottsdale, Arizona, Stati Uniti, 85054
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California
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Sacramento, California, Stati Uniti
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San Diego, California, Stati Uniti
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Santa Ana, California, Stati Uniti
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Santa Rosa, California, Stati Uniti
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Florida
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Clearwater, Florida, Stati Uniti
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Jacksonville, Florida, Stati Uniti
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Georgia
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Conyers, Georgia, Stati Uniti
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Indiana
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Indianapolis, Indiana, Stati Uniti
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Maine
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Auburn, Maine, Stati Uniti
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North Carolina
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Charlotte, North Carolina, Stati Uniti
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Oregon
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Portland, Oregon, Stati Uniti
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Tennessee
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Knoxville, Tennessee, Stati Uniti
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Texas
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Dallas, Texas, Stati Uniti
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San Antonio, Texas, Stati Uniti
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Virginia
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Norfolk, Virginia, Stati Uniti
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Richmond, Virginia, Stati Uniti
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 40 anni a 80 anni (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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:
- 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
- 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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: Sapropterin dihydrochloride
Subjects receive 400 mg oral sapropterin dihydrochloride twice daily for 24 weeks.
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Subjects receive 400 mg oral sapropterin dihydrochloride twice daily for 24 weeks.
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Comparatore placebo: Placebo
Subjects receive matching oral Placebo twice daily for 24 weeks.
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Subjects receive matching oral Placebo twice daily for 24 weeks.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Change in Peak Walking Time (PWT) From Baseline
Lasso di tempo: Baseline and up to Week 24
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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).
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Baseline and up to Week 24
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Number of Subjects With Adverse Events (AEs)
Lasso di tempo: Up to 24-weeks
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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.
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Up to 24-weeks
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Change in Claudication Onset Time (COT) From Baseline
Lasso di tempo: Baseline and up to Week 24
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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.
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Baseline and up to Week 24
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Altre misure di risultato
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Change in Peak Walking Time From Baseline With and Without Vitamin C
Lasso di tempo: Baseline up to 24 weeks
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The first 50% of subjects enrolled in the study were randomized to receive sapropterin dihydrochloride at 400 mg BID or oral placebo BID alone (without vitamin C).
When approximately 50% enrollment was met, 1000 mg/day vitamin C was added to the dose regimen of newly enrolled subjects in both sapropterin dihydrochloride and placebo treatment groups given orally in two divided doses of 500 mg with study drug.
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Baseline up to 24 weeks
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Collegamenti utili
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 dicembre 2006
Completamento primario (Effettivo)
1 novembre 2008
Completamento dello studio (Effettivo)
1 gennaio 2009
Date di iscrizione allo studio
Primo inviato
21 novembre 2006
Primo inviato che soddisfa i criteri di controllo qualità
21 novembre 2006
Primo Inserito (Stima)
23 novembre 2006
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
7 gennaio 2021
Ultimo aggiornamento inviato che soddisfa i criteri QC
14 dicembre 2020
Ultimo verificato
1 dicembre 2020
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattia cardiovascolare
- Malattie vascolari
- Arteriosclerosi
- Malattie arteriose occlusive
- Aterosclerosi
- Malattia arteriosa periferica
- Malattie vascolari periferiche
- Claudicazione intermittente
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antiaritmici
- Agenti vasodilatatori
- Modulatori di trasporto a membrana
- Ormoni e agenti regolatori del calcio
- Bloccanti dei canali del calcio
- Verapamil
Altri numeri di identificazione dello studio
- PAD-001
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .