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PTC124 for Cystic Fibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00234663
Recruitment Status : Completed
First Posted : October 7, 2005
Last Update Posted : January 13, 2009
Cystic Fibrosis Foundation
FDA Office of Orphan Products Development
Information provided by:
PTC Therapeutics

Brief 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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: PTC124 Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis
Study Start Date : September 2005
Actual Primary Completion Date : August 2006
Actual Study Completion Date : August 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Primary Outcome Measures :
  1. CFTR activity as assessed by nasal transepithelial potential difference (TEPD)

Secondary Outcome Measures :
  1. Side effects
  2. Presence of CFTR protein and mRNA
  3. Compliance with treatment
  4. Lung function
  5. PTC124 pharmacokinetics

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of CF based on documented evidence of a conclusively abnormal sweat test (sweat chloride >60 mEq/liter).
  • Abnormal chloride secretion as measured by TEPD (a less than -5 mV TEPD assessment of chloride secretion with chloride-free amiloride and isoproterenol).
  • Presence of a nonsense mutation in one of the alleles of the CFTR gene.
  • Age ≥18 years.
  • Body weight ≥40 kg.
  • FEV1 ≥40% of predicted for age, gender, and height (Knudson standards).
  • Oxygen saturation (as measured by pulse oximetry) ≥92% on room air.
  • Willingness of male and female patients, if not surgically sterile, to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and follow-up periods.
  • Negative pregnancy test (for females of childbearing potential).
  • Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, and study restrictions.
  • Ability to provide written informed consent.

Exclusion Criteria:

  • Prior or ongoing medical condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the patient, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
  • Ongoing acute illness including acute upper or lower respiratory infections within 2 weeks before start of study treatment.
  • History of major complications of lung disease within 2 months prior to start of study treatment.
  • Abnormalities on screening chest x-ray suggesting clinically significant active pulmonary disease other than CF, or new, significant abnormalities that may be indicative of clinically significant active pulmonary involvement secondary to CF.
  • Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test.
  • Hemoglobin <10 g/dL.
  • Serum albumin <2.5 g/dL.
  • Abnormal liver function (serum ALT, AST, GGT, alkaline phosphatase, LDH, or total bilirubin > upper limit of normal).
  • Abnormal renal function (serum creatinine >1.5 times upper limit of normal).
  • Pregnancy or breast-feeding.
  • History of solid organ or hematological transplantation.
  • Exposure to another investigational drug within 14 days prior to start of study treatment.
  • Ongoing participation in any other therapeutic clinical trial.
  • Ongoing use of thiazolidinedione peroxisome proliferator-activated receptor gamma (PPAR γ) agonists, eg, rosiglitazone (Avandia® or equivalent) or pioglitazone (Actos® or equivalent)
  • Change in intranasal medications (including use of corticosteroids, cromolyn, ipratropium bromide, phenylephrine, or oxymetazoline) within 14 days prior to start of study treatment.
  • Change in treatment with systemic or inhaled corticosteroids within 14 days prior to start of study treatment.
  • Use or requirement for inhaled gentamicin or amikacin within 14 days prior to start of study treatment or during study treatment.
  • Requirement for systemic aminoglycoside antibiotics within 14 days prior to start of study treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00234663

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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233-1711
United States, California
Stanford University Medical Center
Palo Alto, California, United States, 94304-5786
United States, Colorado
The Children's Hospital
Denver, Colorado, United States, 80218
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Ohio
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
PTC Therapeutics
Cystic Fibrosis Foundation
FDA Office of Orphan Products Development
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Principal Investigator: John P Clancy, MD University of Alabama at Birmingham

Layout table for additonal information Identifier: NCT00234663    
Other Study ID Numbers: PTC124-GD-003-CF
1R01FD003009-01 ( U.S. FDA Grant/Contract )
First Posted: October 7, 2005    Key Record Dates
Last Update Posted: January 13, 2009
Last Verified: January 2009
Keywords provided by PTC Therapeutics:
Cystic fibrosis
Nonsense mutation
Premature stop codon
Additional relevant MeSH terms:
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Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases