Safety and Efficacy of Ataluren (PTC124) for Cystic Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00237380
• Date of registration: 07/10/2005
• Prospective Registration: Yes
• Primary sponsor: PTC Therapeutics
• Public title: Safety and Efficacy of Ataluren (PTC124) for Cystic Fibrosis
• Scientific title: A Phase 2 Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis
• Date of first enrolment: November 30, 2005
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00237380
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Israel

Contacts

• Name: Eiten Kerem, MD
• Affiliation: Hadassah University Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of CF based on documented evidence of a conclusively abnormal sweat test
(sweat chloride >60 milliequivalents/litre [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.

- Forced expiratory volume in 1 second (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 participants, 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 participant, 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 grams per deciliter (g/dL).

- Serum albumin <2.5 g/dL.

- Abnormal liver function (serum alanine aminotransferase [ALT], aspartate
aminotransferase [AST], gamma-glutamyl transferase [GGT], alkaline phosphatase,
lactate dehydrogenase [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 ?) 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Ataluren

Primary Outcome(s)

Number of Participants With a Chloride Transport Normalization Between Baseline and End of Treatment [Time Frame: Baseline of Cycle 1 and Cycle 2 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)]

Number of Participants With a Chloride Transport Response [Time Frame: Baseline of Cycle 1 and Cycle 2 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)]

Change From Baseline to End of Treatment in Total Chloride Transport [Time Frame: Baseline of Cycle 1 and Cycle 2, Day 14 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)]

Secondary Outcome(s)

Change From Baseline in CFTR Protein in Nasal Mucosa as Determined by Immunofluorescence [Time Frame: Baseline of Cycle 1 and Cycle 2, Day 14 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)]

Change From Baseline in Nonsense Mutation CFTR mRNA in Nasal Mucosa as Determined by Quantitative Polymerase Chain Reaction (PCR) Assay [Time Frame: Baseline of Cycle 1 and Cycle 2, Day 14 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)]

Change From Baseline in Number of Neutrophils in Blood [Time Frame: Baseline Up to Day 56]

Compliance with Study Treatment [Time Frame: Baseline Up to Day 56]

PK: Maximum Plasma Concentration (Cmax) of Ataluren [Time Frame: 0 (predose), 1, 2, 3, and 4 hrs postdose of the morning dose; 0 (predose), 1, 2, 3, and 4 hrs postdose of the midday dose; and 0 hrs (predose), 1, 2, 3, 4, and 12 hrs postdose of the evening dose on Days 1 and 13 of Cycles 1 and 2 (1 cycle=28 days)]

Change From Baseline in Nasal Chloride Secretion as Assessed by Transepithelial Potential Difference (TEPD) [Time Frame: Baseline of Cycle 1 and Cycle 2, Day 14 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)]

Change From Baseline in Pulmonary Function as Measured by Spirometry [Time Frame: Baseline of Cycle 1 and Cycle 2, Day 14 of Cycle 1 and Cycle 2 (1 cycle=28 days)]

PK: Area Under the Plasma Concentration Time Curve (AUC) of Ataluren [Time Frame: 0 (predose), 1, 2, 3, and 4 hrs postdose of the morning dose; 0 (predose), 1, 2, 3, and 4 hrs postdose of the midday dose; and 0 hrs (predose), 1, 2, 3, 4, and 12 hrs postdose of the evening dose on Days 1 and 13 of Cycles 1 and 2 (1 cycle=28 days)]

PK: Terminal Elimination Half Life (T1/2) of Ataluren [Time Frame: 0 (predose), 1, 2, 3, and 4 hrs postdose of the morning dose; 0 (predose), 1, 2, 3, and 4 hrs postdose of the midday dose; and 0 hrs (predose), 1, 2, 3, 4, and 12 hrs postdose of the evening dose on Days 1 and 13 of Cycles 1 and 2 (1 cycle=28 days)]

Change From Baseline in Body Weight [Time Frame: Baseline of Cycle 1 and Cycle 2, Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)]

Change From Baseline in Sweat Chloride Concentration as Determined by Pilocarpine Iontophoresis [Time Frame: Baseline, Day 41]

Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of Ataluren [Time Frame: 0 (predose), 1, 2, 3, and 4 hours (hrs) postdose of the midday dose; 0 (predose), 1, 2, 3, 4, and 12 hrs postdose of the evening dose on Day 1 and Day 27]

Secondary ID(s)

20050188

PTC124-GD-005-CF

Source(s) of Monetary Support

Please refer to primary and secondary sponsors