E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
cystic fibrosis and chronic infection of lower respiratory tract with Pseudomonas aeruginosa |
|
E.1.1.1 | Medical condition in easily understood language |
cystic fibrosis and chronic lung infection with a bacterium (germ) called Pseudomonas aeruginosa |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate safety of treatment with AZLI 75 mg 3 times daily (TID) for 3 courses of therapy (28 days on/28 days off) in female and male children less than 13 years of age with CF and chronic PA infection/colonization. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Aged 12 years or less.
• Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria: sweat chloride level ≥ 60 mEq/L by quantitative pilocarpine iontophoresis; or a genotype with 2 identifiable mutations consistent with CF; or an abnormal nasal transepithelial potential difference (NPD), and 1 or more clinical features consistent with CF.
• Documented positive lower respiratory tract culture for PA at the screening visit plus 2 documented positive lower respiratory tract cultures for PA within 12 months prior to study entry (start of treatment).
• Clinically stable with no evidence of significant respiratory symptoms or, if obtained for clinical evaluation, no chest radiograph findings at screening that would require administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization. |
|
E.4 | Principal exclusion criteria |
• Use of IV or inhaled antipseudomonal antibiotics within 14 days of study entry (start of treatment).
• Presence of a condition or abnormality that would compromise the participant’s safety or the quality of study data, in the opinion of the investigator.
• History of hypersensitivity/adverse reaction to aztreonam or beta-agonists.
• Use of any investigational drug within 30 days of study entry (start of treatment). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of subjects who have discontinued the study drug due to safety or tolerability reasons by Day 168. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Between baseline (Day 1) and Day 168. |
|
E.5.2 | Secondary end point(s) |
For subjects aged 6 years or more:
• Change in FEV1 % predicted at end of each 28-day-on-treatment cycle of AZLI
• Change in CFQ-R respiratory symptoms scale (RSS) score at the end of each 28-day-on-treatment cycle of AZLI
For all subjects:
• Change in PA sputum density at end of each 28-day-on-treatment cycle of AZLI
• Use of additional antipseudomonal antibiotics
• Number and duration of hospitalizations
• Number and time to PA exacerbations
• Study-drug induced bronchospasm
• Adverse event rates adjusted for study duration |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
For subjects aged 6 years or more at Days 28, 84, and 140:
• Change from baseline in FEV1 % predicted
• Change from baseline in CFQ-R respiratory symptoms scale (RSS) score
For all subjects at Days 28, 84 and 140:
• Change from baseline in PA sputum density
For all subjects from baseline to end of treatment (Day 140):
• Study-drug induced bronchospasm
For all subjects from screening to end of study (Day 168):
• Use of additional antipseudomonal antibiotics
• Number and duration of hospitalizations
• Number and time to PA exacerbations
• Adverse event rates adjusted for study duration |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Date of last study visit of last study subject. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |