Cystic Fibrosis MedDRA version: 9.1 Level: LLT Classification code 10011762 Term: Cystic fibrosis
Conditions
Interventions
Product Code: PTC124
Pharmaceutical Form: Oral powder
Current Sponsor code: PTC124
Concentration unit: % (W/W) percent weight/weight
Concentration type: equal
Concentration number: 25-
Sponsors
PTC Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of CF based on documented evidence of a conclusively abnormal sweat test (sweat chloride >35 mEq/liter by pilocarpine iontophoresis). Note: A patient does not need to have a repeat sweat test solely for enrollment into this study if documentation of an abnormal sweat test is already available. 2. Abnormal nasal epithelial TEPD total chloride conductance (a less electrically negative value than 5 mV for ?chloride-free+isoproterenol). Note: Even if a patient has past documentation of an abnormal TEPD, the TEPD must be repeated as part of the screening procedures and must be abnormal (taken as a mean of both nostrils if values for both nostrils are available). A patient requiring inhaled tobramycin (eg, TOBI®) should have the baseline TEPD assessed while receiving a course of inhaled tobramycin. 3. Presence of a mutation in both alleles of the cftr gene with a premature stop (nonsense) mutation in at least one of the alleles of the gene (ie, patient should be either heterozygous or homozygous for stop mutation). 4. Documentation that a blood sample has been drawn for reconfirmation of the presence of a nonsense mutation in the cftr gene. Note: A patient who has documentation of a nonsense mutation need not wait for confirmatory results to start study therapy as long as a blood sample has been drawn for reconfirmation. 5. Age >/=6 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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 human immunodeficiency virus (HIV) test. 7. Hemoglobin the upper limit of normal, or serum ALT, AST, or GGT >2.0 times the upper limit of normal). Note: A patient who are taking ursodiol tablets (eg, URSO®) may be enrolled as long as these liver function test values are within the designated limits. 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 ?) agonists, eg, rosiglitazone (Avandia® or equivalent) or pioglitazone (Actos® or equivalent). 16. Requirement for treatment with intranasal or inhaled medications (including use of cromolyn, ipratropium bromide, phenylephrine, or oxymetazoline) within 7 days prior to start of study treatment. Note: A patient may receive inhaled ß-agonist therapy as clinically necessary for acute pulmonary exacerbations during the study, although, if medically appropriate, an attempt should be made to avoid such use. 17. Requirement for treatment with systemic or inhaled corticosteroids within 7 days prior to start of study treatment. Note: A patient may receive inhaled corticosteroids as clinically necessary for acute pulmonary exacerbations during the study, although, if medically appropriate, an attempt should be made to avoid their use. 18. Use of or requirement for inhaled gentamicin or amikacin within 14 days prior to start of study treatment or during study treatment. Note: A patient may receive inhaled tobramycin (eg, TOBI®) before and during the study but use of inhaled tobramycin should not be changed or initiated during the study. 19. Requirement for systemic aminoglycoside antibiotics within 14 days prior to start of study treatment. Note: A patient may receive systemic antibiotics as clinically necessary for acute pulmonary exacerbations during the study, although, if medically appropriate, an attempt should be made to avoid systemic aminoglycoside antibiotics. Note: A patient may receive inhaled dornase alpha (Pulmozyme®) or bronchodilators before and during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine whether PTC124 safely provides pharmacological activity as evaluated by TEPD assessment of chloride conductance;Secondary Objective: • To assess PTC124 effects on additional TEPD measures of ion channel activity • To evaluate PTC124 effects on CFTR protein and CFTR mRNA in nasal mucosa • To assess inflammatory markers in sputum and serum • To characterize changes in pulmonary function • To evaluate changes in patient weight • To determine compliance with PTC124 therapy • To further characterize the safety profile of PTC124 in patients with CF • To further evaluate the PK profile of PTC124 in patients with CF • To assess changes in disease-related symptoms over the course of treatment ;Primary end point(s): • Changes in total nasal chloride conductance as assessed by TEPD, with assessment of mean changes in TEPD by dose level and the proportion of patients with a chloride conductance response by dose level; a chloride conductance response is defined as at least a -5 mV (or more negative) improvement in TEPD following sequential perfusion with a chloride-free amiloride, 100 ?M, solution and the same solution with isoproterenol, 10 ?M, for 3 minutes each (?chloride-free+isoproterenol) | — |
Countries
Belgium
Outcome results
None listed