PTC124 for Cystic Fibrosis
Summary
In some patients with cystic fibrosis (CF), the disease is caused by a nonsense mutation (premature stop codon) in the gene that makes the cystic fibrosis transmembrane regulator (CFTR) protein. PTC124 has been shown to partially restore CFTR production in animals with CF due to a nonsense mutation. The main purpose of this study is to understand whether PTC124 can safely increase functional CFTR protein in the cells of patients with CF due to a nonsense mutation.
Description
In this study, patients with CF due to a nonsense mutation will be treated with a new investigational drug called PTC124. Evaluation procedures (history, physical examination, blood and urine tests to assess organ function, electrocardiogram (ECG), chest x-ray, and CF-specific tests) to determine if a patient qualifies for the study will be performed within 21 days prior to the start of treatment. Eligible patients who elect to enroll in the study will then participate in two 28-day treatment and follow-up periods (56 days total). Within the first 28-day period, PTC124 treatment will be taken 3 times per day with meals for 14 days at doses of 4 mg/kg (breakfast), 4 mg/kg (lunch) and 8 mg/kg (dinner); there will then be an interval of 14 days without treatment. Within the second 28-day period, PTC124 treatment will be taken 3 times per day with meals for 14 days at doses of 10 mg/kg (breakfast), 10 mg/kg (lunch) and 20 mg/kg (dinner); there will then be an interval of 14 days without treatment. There will be a 2-night stay at the clinical research center at the beginning and at the end of each 14 days of PTC124 treatment, which means that there will be four 2-night stays at the clinical research center during the study. During the study, PTC124 efficacy, safety, and pharmacokinetics will be evaluated periodically with measurement of transepithelial potential difference (TEPD), nasal mucosal brushing to assess for cellular CFTR mRNA and protein, medical history, physical examinations, blood tests, urinalysis, ECGs, chest x-ray, and pulmonary function tests.
Study Design
Allocation: Non-Randomized, Control: Dose Comparison, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Cystic Fibrosis
Intervention
PTC124
Location
University of Alabama at Birmingham
Birmingham
Alabama
United States
35233-1711
Status
Completed
Source
PTC Therapeutics
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00234663
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Cystic Fibrosis
An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.
Cystic Fibrosis Transmembrane Conductance Regulator
A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)
Mice, Inbred Cftr
A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.
Stenotrophomonas Maltophilia
A species of STENOTROPHOMONAS, formerly called Xanthomonas maltophilia, which reduces nitrate. It is a cause of hospital-acquired ocular and lung infections, especially in those patients with cystic fibrosis and those who are immunosuppressed.
Drainage, Postural
A rehabilitation therapy for removal of copious mucus secretion from the lung of patients with diseases such as CHRONIC BRONCHITIS; BRONCHIECTASIS; PULMONARY ABSCESS; or CYSTIC FIBROSIS. The patient's head is placed in a downward incline (so the TRACHEA is inferior to the affected area) for 15- to 20-minute sessions.
Clinical Trials
PTC124 for Pediatric Patients With Cystic Fibrosis
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Study of Ataluren (PTC124™) in Cystic Fibrosis
Cystic fibrosis (CF) is a genetic disorder caused by a mutation in the gene that makes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A specific type of mutation c...
Extension Study of Ataluren (PTC124) in Cystic Fibrosis
Cystic fibrosis (CF) is a genetic disorder caused by a mutation in the gene that makes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A specific type of mutation c...
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Exercise-Induced Bronchospasm in Cystic Fibrosis
Exercise is an important clinical feature in cystic fibrosis. Better exercise capacity has been associated with better patient outcomes and quality of life. Exercise-induced bronchospasm...
PubMed Articles
New therapies in cystic fibrosis.
Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that lead to abnormalities in transepithelial ion transport in the airways of affected pat...
A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.
Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis.
Treatment of cystic fibrosis associated cutaneous vasculitis with chloroquine.
Vasculitis is a well recognised complication of Cystic Fibrosis. Corticosteroids are the mainstay of treatment but some cases can be resistant and may require additional disease modifying agents. We d...
First report of cystic fibrosis mutations in Libyan cystic fibrosis patients.
Background: There are few data on the molecular basis of Cystic Fibrosis (CF) in North Africa, probably due to under-diagnosis. Aim: This is the first study of cystic fibrosis transmembrane conductanc...
