Clinical Trials

Sapropterin dihydrochloride has been evaluated across Phase 1 through Phase 4 in numerous clinical trials investigating therapeutic efficacy, safety, and long-term treatment responses. Research focuses on metabolic disorders such as phenylketonuria, hyperphenylalaninemia, and GTP cyclohydrolase deficiency, alongside cardiovascular and gastrointestinal indications including intermittent claudication, gastroparesis, hypertension, and liver cirrhosis. Sponsored by both pharmaceutical entities and academic medical centers, these trials encompass recruitment statuses ranging from completed and actively recruiting to terminated or withdrawn.

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT07574034 NOT_YET_RECRUITING
Multisystemic Smooth Muscle Dysfunction Syndrome
Gregor Andelfinger
 2026-06-01
NCT07255599 ACTIVE_NOT_RECRUITING
Phenylketonuria (PKU)
Sohag University
 2025-09-01 PHASE1
NCT06987773 COMPLETED
Bioequivalence
APR Applied Pharma Research s.a.
 2025-08-20 PHASE1
NCT06396637 UNKNOWN
Pancreatic Adenocarcinoma Metastatic
Sun Yat-sen University
 2024-04-30 PHASE2
NCT06481709 COMPLETED
Bioavailability
APR Applied Pharma Research s.a.
 2024-07-30 PHASE1
NCT01965912 COMPLETED
Phenylketonuria
BioMarin Pharmaceutical
 2013-10 PHASE4
NCT05299203 UNKNOWN
Head and Neck Squamous Cell Carcinoma
West China Hospital
 2022-05 PHASE1
NCT04054973 WITHDRAWN
Schizo Affective Disorder; Schizophrenia
University of Massachusetts, Worcester
 2019-09-11 PHASE2
NCT03493412 WITHDRAWN
Peripheral Artery Disease; Peripheral Arterial Disease
University of Nebraska
 2019-07-01 PHASE4
NCT00838435 COMPLETED
Phenylketonuria
BioMarin Pharmaceutical
 2009-02 PHASE3
NCT01439555 COMPLETED
Alzheimer's Disease
University of Massachusetts, Worcester
 2011-11 PHASE2
NCT01977820 TERMINATED
Phenylketonuria
BioMarin Pharmaceutical
 2014-02 PHASE2
NCT01376908 COMPLETED
Phenylketonuria
BioMarin Pharmaceutical
 2011-06 PHASE3
NCT01732471 COMPLETED
Phenylketonuria
Merck KGaA, Darmstadt, Germany
 2012-11 PHASE3
NCT01456286 COMPLETED
Liver Cirrhosis; Portal Hypertension
Fundacion Clinic per a la Recerca Biomédica
 2011-10 PHASE2; PHASE3
NCT01425528 COMPLETED
GTP Cyclohydrolase Deficiency
University of Utah
 2011-08 PHASE1; PHASE2
NCT01395394 TERMINATED
Phenylketonuria
Emory University
 2011-06 PHASE2
NCT01114737 COMPLETED
Phenylketonuria
BioMarin Pharmaceutical
 2010-08 PHASE3
NCT01135186 COMPLETED
Gastroparesis
Stanford University
 2010-05
NCT01732471 Completed
Phenylketonuria
Merck KGaA Darmstadt Germany
 2012-11 Phase 3
NCT01541397 TERMINATED
Hyperphenylalaninemia; Phenylketonuria
The University of Texas Health Science Center, Houston
 2011-06
NCT01412437 WITHDRAWN
PKU
Children's National Research Institute
 2011-04
NCT00943579 COMPLETED
Autistic Disorder
The Children's Health Council
 2009-08 PHASE2; PHASE3
NCT01141595 COMPLETED
Autism Spectrum Disorder
The University of Texas Health Science Center, Houston
 2010-07
NCT00850070 COMPLETED
Autistic Disorder
The Children's Health Council
 2009-03 PHASE2
NCT00986973 COMPLETED
Phenylketonuria
Children's Hospital of Philadelphia
 2010-03
NCT00935753 WITHDRAWN
Behavioral Manifestations of Lesch-Nyhan Disease
University of California, San Diego
 2009-04 PHASE2; PHASE3
NCT00332189 COMPLETED
Phenylketonuria
BioMarin Pharmaceutical
 2006-07 PHASE3
NCT00789568 COMPLETED
Phenylketonuria
BioMarin Pharmaceutical
 2008-10 PHASE1
NCT00403494 COMPLETED
Intermittent Claudication
BioMarin Pharmaceutical
 2006-12 PHASE2
NCT00532844 COMPLETED
Endothelial Dysfunction
BioMarin Pharmaceutical
 2007-09 PHASE2
NCT00435331 COMPLETED
Pulmonary Arterial Hypertension
Vanderbilt University
 2008-03 PHASE1
NCT00445978 COMPLETED
Sickle Cell Disease
BioMarin Pharmaceutical
 2007-05 PHASE2
NCT00325962 COMPLETED
Hypertension
BioMarin Pharmaceutical
 2006-05 PHASE2
NCT00225615 COMPLETED
Phenylketonurias
BioMarin Pharmaceutical
 2005-11 PHASE3
NCT00104247 COMPLETED
Phenylketonurias
BioMarin Pharmaceutical
 2005-03 PHASE3
NCT00272792 COMPLETED
Phenylketonurias
BioMarin Pharmaceutical
 2006-02 PHASE3
NCT00104260 COMPLETED
Phenylketonurias
BioMarin Pharmaceutical
 2004-12 PHASE2

(data from https://clinicaltrials.gov, updated on 2026-05-07)

Check the Sapropterin (Tetrahydrobiopterin) Dihydrochloride product page for in-depth specifications, including solubility, stock solutions, MOA, and working concentrations.

Compliance for Clinical Use

Mechanism and Biochemical Profile

Sapropterin dihydrochloride acts as a synthetic form of natural tetrahydrobiopterin (BH4) that directly binds to and activates phenylalanine hydroxylase, promoting the enzymatic conversion of L-phenylalanine to L-tyrosine and restoring functional catabolic metabolic flux. By enhancing residual hydroxylase activity and preventing neurotoxic phenylalanine accumulation, this targeted activation directly supports its clinical utility in treating phenylketonuria and related hyperphenylalaninemia spectrum disorders.

Appendix RUO and cGMP Quality Standards

Quality Dimension RUO (Research Use Only) cGMP (Current Good Manufacturing Practice)
Clinical Applicability Prohibited in human clinical trials or medical diagnostics. Mandatory for human clinical trials (Phase I–III) and therapies.
Regulatory Status Non-regulated grade; exempt from drug manufacturing laws. Legally enforced by health authorities (e.g., FDA, EMA, NMPA).
Facility Environment Unclassified analytical or research laboratories. Validated Cleanrooms (ISO Class 5–8) with continuous monitoring.
Quality Control Basic purity and activity testing. Rigorous safety release testing (Sterility, Endotoxin, Mycoplasma).
Process Validation Basic equipment calibration; no process validation required. Full qualification (IQ/OQ/PQ) and complete batch records.
Quality Assurance Vendor self-declared without required formal QMS. Mandatory QA/QC unit, Change Control, CAPA, and vendor audits.
Regulatory Impact High risk of IND rejection if used as a critical raw material. Required for IND/NDA filings, supported by Drug Master Files (DMF).

Footnotes

Regulatory Note: Governed by FDA (21 CFR Parts 210/211/312), EMA (EudraLex Vol 4), ICH Guidelines (E6/Q7/Q9/Q10), and compendial standards (USP <71>/<85>/<1043>).

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Note: Technical data last updated: Sep 1, 2026.