Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

PTC124 for Pediatric Patients With Cystic Fibrosis

This study has been completed.
Information provided by:
PTC Therapeutics Identifier:
First received: April 6, 2007
Last updated: April 1, 2009
Last verified: April 2009
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 Intervention Phase
Cystic Fibrosis
Drug: PTC124
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis

Resource links provided by NLM:

Further study details as provided by PTC Therapeutics:

Primary Outcome Measures:
  • CFTR activity as assessed by nasal transepithelial difference (TEPD)

Secondary Outcome Measures:
  • Side effects
  • Presence of CFTR protein and mRNA
  • Compliance with treatment
  • Lung function
  • Sputum test
  • Sweat test
  • Body weight
  • PTC124 pharmacokinetics

Estimated Enrollment: 30
Study Start Date: March 2007
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
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 with nonsense-mutation-mediated CF will receive two repeated 28-day cycles, each comprising 14 days on therapy and 14 days off therapy. In a crossover design, patients will be randomized to receive PTC124 treatment in Cycle 1 by either of the following regimens:

  • PTC124, given 3 times per day (TID) with a regimen of 4 mg/kg at breakfast, 4 mg/kg at lunch, and 8 mg/kg at dinner, or
  • PTC124, given 3 times per day (TID) with a regimen of 10 mg/kg at breakfast, 10 mg/kg at lunch and 20 mg/kg at dinner.

In Cycle 2, patients will then receive the drug according to the regimen opposite from that given in Cycle 1.

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, sputum test, urinalysis, ECGs, chest x-ray, and pulmonary function tests.


Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria: Patients must meet all of the following conditions to be eligible for enrollment into the study:

  1. Diagnosis of CF based on conclusively abnormal sweat test (sweat chloride >35 mEq/liter.
  2. Abnormal nasal epithelial TEPD total chloride conductance (a more electrically negative value than 5 mV for Δchloride-free+isoproterenol).
  3. Presence of a mutation in both alleles.
  4. Documentation that a blood sample has been drawn for reconfirmation of the presence of a nonsense mutation in the cftr gene.
  5. Age ≥6 years.
  6. Body weight ≥25 kg.
  7. FEV1 ≥40% of predicted for age, gender, and height.
  8. Oxygen saturation ≥92% on room air.
  9. 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.
  10. Negative pregnancy test (for females of childbearing potential).
  11. Willingness and ability to comply with scheduled visits, drug administration plan, study procedures (including TEPD measurements, clinical laboratory tests, pulmonary function tests, and PK sampling), and study restrictions.
  12. Ability to provide written informed consent and/or assent.
  13. Evidence of signed and dated informed consent document (by the patient or a legal guardian) indicating that the patient and/or the legal guardian has been informed of all pertinent aspects of the trial.

Exclusion Criteria: The presence of any of the following conditions will exclude a patient from enrollment in the study:

  1. Prior exposure to PTC124.
  2. Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse, psychiatric 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.
  3. Ongoing acute illness including acute upper or lower respiratory infections within 2 weeks before start of study treatment.
  4. History of major complications of lung disease (including recent massive hemoptysis or pneumothorax) within 2 months prior to start of study treatment.
  5. Abnormalities on screening chest x-ray suggesting clinically significant active pulmonary disease other than CF, or new, significant abnormalities such as atelectasis or pleural effusion which may be indicative of clinically significant active pulmonary involvement secondary to CF.
  6. Positive hepatitis B surface antigen, hepatitis C antibody test, or HIV test.
  7. Hemoglobin <10 g/dL.
  8. Serum albumin <2.5 g/dL.
  9. Abnormal liver function (serum total bilirubin > the upper limit of normal, or serum ALT, AST, or GGT >2.0 times the upper limit of normal).
  10. Abnormal renal function (serum creatinine >1.5 times upper limit of normal).
  11. Pregnancy or breast-feeding.
  12. History of solid organ or hematological transplantation.
  13. Exposure to another investigational drug within 14 days prior to start of study treatment.
  14. Ongoing participation in any other therapeutic clinical trial.
  15. Ongoing use of thiazolidinedione peroxisome proliferator-activated receptor gamma (PPAR γ) agonists, eg, rosiglitazone (Avandia® or equivalent) or pioglitazone (Actos® or equivalent).
  16. Change in intranasal medications (including use of corticosteroids, cromolyn, ipratropium bromide, phenylephrine, or oxymetazoline) within 14 days prior to start of study treatment.
  17. Change in treatment with systemic or inhaled corticosteroids within 14 days prior to start of study treatment.
  18. Use of or requirement for inhaled gentamicin or amikacin within 14 days prior to start of study treatment or during study treatment.
  19. Requirement for systemic aminoglycoside antibiotics within 14 days prior to start of study treatment.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00458341

Reine Fabiola Hospital
Brussels, Belgium, 1020
UZ Gasthuisberg Leuven
Leuven, Belgium, 3000
Hopital Necker Enfants Malades
Paris, France, 75015
Sponsors and Collaborators
PTC Therapeutics
Principal Investigator: Isabelle Sermet-Gaudelus, MD Hopital Necker
  More Information

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00458341     History of Changes
Other Study ID Numbers: PTC124-GD-006-CF
Study First Received: April 6, 2007
Last Updated: April 1, 2009

Keywords provided by PTC Therapeutics:
Cystic fibrosis
Nonsense mutation
Premature stop codon

Additional relevant MeSH terms:
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases processed this record on April 25, 2017