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 |
|
E.1.1.1 | Medical condition in easily understood language |
Cystic fibrosis and a newly acquired lung infection with a bacterium 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 | 20.0 |
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 | 100000004862 |
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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 |
The primary objective of this study is to evaluate the safety and efficacy of a 14-day course vs a 28-day course of AZLI 75 mg three times a day (TID) in subjects with new onset PA respiratory tract colonization/infection as determined by PA eradication over a 28-day post-treatment follow-up period. |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the time from primary eradication to PA recurrence over a 108-week
post-treatment follow-up period.
- To compare the efficacy of AZLI 75 mg TID for 14 days vs historical pooled tobramycin nebulizer solution (TNS) twice daily (BID) for 28 days as determined by PA eradication over a 28-day post-treatment follow-up period
- To evaluate the time to PA recurrence for a sub-group of subjects matching the population in the TNS ELITE Study over a 108-week post-treatment follow-up period |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female aged 3 months to less than 18 years at screening
2) Diagnosis of CF as determined by the 2008 CF Consensus Conference criteria
3) Documented new onset of positive respiratory tract culture for PA within 30 days of Screening 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)
4) FEV1 ≥ 80% predicted
5) Clinically stable with no evidence of acute significant respiratory symptoms that would require administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization
6) A negative serum pregnancy test is required for female subjects of child bearing potential who have a positive urine pregnancy test at screening
7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
8) Lactating females must agree to discontinue nursing before administration of study drug
9) Subjects and/or parent/guardian must be able to give written informed consent prior to study related procedures |
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E.4 | Principal exclusion criteria |
1) Use of IV or inhaled antipseudomonal antibiotics within 2 years of Screening
2) Use of oral antipseudomonal antibiotics for a respiratory event within 30 days of study entry (Screening visit)
3) History of intolerance to inhaled short acting β2 agonists
4) History of lung transplantation
5) Administration of any investigational drug or device within 28 days prior to Screening
6) Concurrent use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone per day or 20 mg prednisone every other day
7) Current requirement for daily continuous oxygen supplementation or requirement of more than 2 L/minute at night
8) Hospitalization for a respiratory event within 30 days prior to Screening
9) Changes in antimicrobial, bronchodilator, corticosteroid, dornase alfa, or hypertonic saline medications within 7 days prior to Screening
10) Significant changes (per investigators discretion) in physiotherapy technique or schedule within 7 days prior to Screening
11) Abnormal hepatic or renal function results at most recent test within the previous 12 months, defined as
- AST or ALT >5 times upper limit of normal (ULN), or
- Serum creatinine > 2 times ULN for age
12) Presence of a condition or abnormality that would, in the opinion of the Investigator, compromise the subject’s safety or the quality of the study data
13) Known hypersensitivity to aztreonam, its metabolites, or formulation excipients present in AZLI
14) Respiratory cultures performed within 2 years prior to Screening that are positive for ANY Burkholderia spp. or NTM |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is:
- The proportion of subjects with PA-negative cultures through 28 days post-treatment in the 14-day treatment group vs 28-day treatment group |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Time from primary eradication to PA recurrence over a 108-week post-treatment follow-up
period
- The proportion of subjects with PA-negative cultures through 28 days post-treatment in the 14-day treatment group vs historical pooled data for PA eradication at 28 days post-treatment in subjects treated with TNS
- Time to PA recurrence for a sub-group of subjects matching the population in the TNS ELITE Study over a 108-week post-treatment follow-up period |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary objectives include the evaluations of the time to recurrence of PA from primary eradication over the 108-week post-treatment follow-up period. Primary eradication is defined as all PA-negative cultures through 28 days post AZLI treatment. Cultures will be obtained at week 16 and then at 12-week intervals during the follow-up time frame. |
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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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 |
Austria |
Belgium |
Denmark |
France |
Germany |
Greece |
Ireland |
Israel |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
|
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |