E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic fibrosis and new onset lower respiratory tract culture positive for Pseudomonas aeruginosa |
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E.1.1.1 | Medical condition in easily understood language |
cystic fibrosis and a newly acquired lung infection with a bacterium (germ) called Pseudomonas aeruginosa |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070608 |
E.1.2 | Term | Infective pulmonary exacerbation of cystic fibrosis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068288 |
E.1.2 | Term | Cystic fibrosis pulmonary exacerbation |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 and efficacy of a 28-day course of AZLI in patients with initial PA pulmonary colonization/infection at Day 28 (end of treatment) and Days 56, 112, and 196 (1, 3, and 6 months after the end of treatment, respectively). |
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E.2.2 | Secondary objectives of the trial |
Below the age of 6 years pharmacokinetic data will be assessed. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Aged 3 months to less than 18 years.
• 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 new onset of positive lower respiratory tract culture for PA within 30 days of study entry (screening visit) defined as either first lifetime documented PA-positive culture, or PA recovered after at least a 2-year history of PA-negative respiratory cultures (at least 2 cultures per year)
• FEV1 ≥ 80% predicted (for subjects ≥ 6 years of age).
• 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. |
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E.4 | Principal exclusion criteria |
• Use of IV or inhaled antipseudomonal antibiotics within 2 years of study entry (screening visit).
• Use of oral antipseudomonal antibiotics within 30 days of study entry (screening visit).
• History of hypersensitivity/adverse reaction to aztreonam, or beta-agonists.
• Use of any investigational drug, or device within 28 days of study entry (screening visit).
• Presence of a condition or abnormality that would compromise the subject's safety or the quality of study data, in the opinion of the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to evaluate the proportion of subjects with PA-negative cultures at all time points during a 6-month monitoring period (through Day 196) after cessation of active treatment; microbiological cultures will be obtained at Baseline, Day 28 (end of treatment), Day 56 (1 month after
completing AZLI), Day 112 (3 months after completing AZLI), and Day 196 (6 months after completing AZLI). PA-specific antibody titers will be obtained at Baseline, Day 28, and Day 196. Safety endpoints will include adverse events, airway reactivity (study drug-induced bronchspasm), vital signs, blood biochemistry
and hematology. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Microbiological cultures will be obtained at Baseline (Day 1), Day 28 (end of treatment), Day 56 (1 month after completing AZLI), Day 112 (3 months after completing AZLI), and Day 196 (6 months after completing AZLI). PA-specific antibody titers will be obtained at Baseline, Day 28, and Day 196. Airway reactivity (study drug-induced bronchospasm) will be assessed at Baseline and Day 28. Blood biochemistry and hematology will be assessed at Screening, Baseline, Day 28 and Day 196. Adverse events and vital signs will be assessed at Screening, Baseline, Day 28, Day 56, Day 112 and Day 196. |
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E.5.2 | Secondary end point(s) |
In subjects ≥ 6 years of age:
• Change from baseline in FEV1 % predicted at Days 28, 56, 112, and 196;
• Change from baseline in CFQ-R Respiratory Symptoms Score (RSS) at Days 28, 56, 112, and 196.
In all subjects:
• Proportion of subjects with PA-negative cultures at Days 28, 56, 112 and 196;
• Use of additional (non-study) antipseudomonal antibiotics (as a marker for PA exacerbation);
• Change from baseline in weight, height, and body mass index (BMI) at Days 28, 56, 112, and 196;
In subjects < 6 years of age:
• Pharmacokinetics: 1 peak plasma sample will be obtained 1 hour after the first dose of AZLI (Day 1); 1 trough plasma sample will be obtained immediately prior to the last dose of AZLI (Day 28). Plasma aztreonam concentrations at each time point will be summarized (mean, median, standard deviation [SD], minimum, maximum, and number of samples). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
In subjects ≥ 6 years of age at Days 28, 56, 112, and 196:
• Change from baseline in FEV1 % predicted;
• Change from baseline in CFQ-R Respiratory Symptoms Score (RSS).
In all subjects at Days 28, 56, 112 and 196:
• Proportion of subjects with PA-negative cultures;
• Change from baseline in weight, height, and body mass index (BMI).
In all subjects at Screening and Days 1, 28, 56, 112 and 196:
• Use of additional (non-study) antipseudomonal antibiotics (as a marker for PA exacerbation).
In subjects < 6 years of age:
• Pharmacokinetics: 1 peak plasma sample will be obtained 1 hour after the first dose of AZLI (Day 1); 1 trough plasma sample will be obtained immediately prior to the last dose of AZLI (Day 28). |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
France |
Germany |
Ireland |
Italy |
Netherlands |
Poland |
Spain |
United States |
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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
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Date of last study visit of last study subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |