A Phase 1 Study to Evaluate Effects of Sapropterin Dihydrochloride on QTc Intervals in Healthy Adult Subjects
Summary
Sapropterin dihydrochloride (subsequently referred to as sapropterin) (Kuvan®) was approved by the FDA for the treatment of hyperphenylalaninemia in 2007. Preclinical and clinical studies and post-marketing surveillance have not demonstrated any specific cardiovascular concerns with sapropterin (Kuvan®). Nonetheless, nonantiarrhythmic drugs may have the potential to prolong QT interval, leading to potentially fatal ventricular tachycardias, including torsades de pointes. As part of the post-marketing commitment, a thorough QT/QTc study will be conducted according to ICH guidelines.
Study Design
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Conditions
Phenylketonuria
Intervention
sapropterin dihydrochloride
Location
PRACS Institute, Ltd.
Fargo
North Dakota
United States
58104
Status
Completed
Source
BioMarin Pharmaceutical
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00789568
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Phenylketonuria, Maternal
A condition occurring in untreated or partially treated females with PHENYLKETONURIA when they become pregnant. This may result in damages to the FETUS, including MICROCEPHALY; MENTAL RETARDATION; congenital heart disease; FETAL GROWTH RETARDATION; and CRANIOFACIAL ABNORMALITIES. (From Am J Med Genet 1997 Mar 3;69(1):89-95)
Phenylketonurias
A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952).
Trans-1,4-bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochlorid...
An anticholesteremic agent that inhibits sterol biosynthesis in animals.
Dihydropteridine Reductase
An enzyme that catalyzes the reduction of 6,7-dihydropteridine to 5,6,7,8-tetrahydropteridine in the presence of NADP+. Defects in the enzyme are a cause of PHENYLKETONURIA II. Formerly listed as EC 1.6.99.7.
Phenylalanine Hydroxylase
An enzyme of the oxidoreductase class that catalyzes the formation of L-TYROSINE, dihydrobiopterin, and water from L-PHENYLALANINE, tetrahydrobiopterin, and oxygen. Deficiency of this enzyme may cause PHENYLKETONURIAS and PHENYLKETONURIA, MATERNAL. EC 1.14.16.1.
Clinical Trials
Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period
The primary objective of the study is to evaluate the proportion of responders [≥30% reduction from baseline in blood phenylalanine (Phe) level] to 20 mg/kg/day sapropterin dihydrochlori...
This double-blind, placebo-controlled, randomized study is designed to evaluate the safety and therapeutic effects of sapropterin dihydrochloride on neuropsychiatric symptoms in subjects w...
The primary objective of this study is to evaluate the efficacy of Phenoptin™ (sapropterin dihydrochloride) in reducing blood phenylalanine (Phe) levels in subjects with phenylketonuria.
The primary objective is to evaluate the degree and frequency of response to Phenoptin™ (sapropterin dihydrochloride), as demonstrated by a reduction in blood phenylalanine (Phe) level a...
PKUDOS: PKU Demographic, Outcomes, and Safety Registry
The objective of this study is to evaluate the safety of long-term treatment with Kuvan.
PubMed Articles
Elevated maternal phenylalanine levels during pregnancy are teratogenic, and may result in embryo-foetopathy, which could lead to stillbirth, significant psychomotor handicaps and birth defects. This...
BACKGROUND: Tetrahydrobiopterin (BH(4))-sensitive phenylketonuria (PKU) can be treated with sapropterin dihydrochloride. We studied metabolic control and health-related quality of life (HRQoL) in PKU...
Protein misfolding with loss-of-function of the enzyme phenylalanine hydroxylase (PAH) is the molecular basis of phenylketonuria in many individuals carrying missense mutations in the PAH gene. PAH is...
Phenylketonuria With Acute Myeloblastic Leukemia in a 9-year-old Boy: Reporting a Rare Case.
Phenylketonuria is a genetic metabolic disorder resulting in phenylalanine accumulation in blood. Phenylacetate, which is an abnormal phenylalanine metabolities, was hypothesized to have anticancer ac...
Phenylketonuria-related synaptic changes in a BTBR-Pah enu2 mouse model.
Phenylketonuria is the most common, inherited aminoacidopathy associated with brain injury. To date, no study has focused on the neuropathology of the genetic mouse model of phenylketonuria, BTBR-Pah...
