E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pseudomonas aeruginosa pulmonary infection / colonisation in patients
with cystic fibrosis |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011763 |
E.1.2 | Term | Cystic fibrosis lung |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 the longer term safety, tolerability and efficacy of Arikace™ 590 mg administered once daily for up to twelve cycles with each cycle consisting of 28 days on-treatment followed by 28 days off treatment. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Written informed consent or assent obtained from the subject, parent or legal guardian to participate in the open label multi-cycle study, TR02-110
2) Subject has completed study TR02-108 or TR02-109, and has been compliant with the study protocol
3) Negative pregnancy result on pregnancy test performed within 2 weeks prior to Day 1 and use of reliable methods of contraception (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD) throughout the study duration in women of child-bearing potential. Women not of childbearing potential are defined as prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile
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E.4 | Principal exclusion criteria |
1) Subject met any of the listed criteria for study drug discontinuation (safety reasons or non-compliance) in protocol TR02-108 or TR02-109
2) Elevated AST, ALT or GGT ≥ 3× the upper limit of normal (ULN) within 4 weeks prior to Day 1
3) Absolute neutrophil count < 1000 within 4 weeks prior to Day 1
4) Serum creatinine > 2× ULN within 4 weeks prior to Day 1
5) Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.
6) History of alcohol, medication, or illicit drug abuse within the 6 months prior to consent
7) Smoking tobacco or any substance within 6 months prior to consent or anticipated inability to refrain from smoking throughout the study
8) Any condition which in the opinion of the investigator interferes with the subject’s ability to safely complete the study or adhere to the study requirements
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Treatment emergent adverse events (AE) up to Day 672
2) Adverse events leading to permanent discontinuation of study drug
3) Serious adverse events (SAE) up to Day 672
4) Laboratory abnormalities up to Day 672
5) Acute tolerability as measured by PFT changes pre to post dose
6) Vital signs and oxygen saturation (change from pre to post-dose) and change from baseline
7) Shift in MICs for Pa and Burkholderia species from Day 1 to Days 169, 337, 505 and 672
8) Proportion of subjects with emergent pathogens
9) Evaluation of audiology
10) Change in serum creatinine throughout study
11) Concomitant medications including antibiotics, antivirals, antifungals and other inhalant medications such as bronchodilators, DNase, inhaled steroids
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After the first phase of the study (6 cycles and ~356 days). Then re-consented patients will enter into a second phase (an additional 6 cycles and ~356 days) |
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E.5.2 | Secondary end point(s) |
1) Relative change in FEV1 [liters], and FEV1 (% predicted) throughout the study
2) Time to first protocol defined pulmonary exacerbation and proportion of subjects experiencing a protocol defined pulmonary exacerbation
3) Time to first antipseudomonal antibiotic treatment for protocol defined pulmonary exacerbation, proportion of subjects initiating treatment and number of days of treatment
Exploratory Endpoints
1) Time to first investigator defined pulmonary exacerbation and proportion of subjects experiencing an investigator defined pulmonary exacerbation
2)Time to first pulmonary exacerbation defined using Seattle Score (Rosenfeld Criteria) and proportion of subjects experiencing a pulmonary exacerbation defined using Seattle Score
3) Time to first antipseudomonal antibiotic treatment for any pulmonary exacerbation (protocol defined or investigator defined), proportion of subjects initiating treatment and number of days of treatment
4) Log CFU Pa and change in log CFU Pa from baseline throughout study
5) Log CFU Burkholderia species and change in log CFU Burkholderia species from baseline throughout study
6) Time to, number of and length of hospitalizations and proportions of subjects hospitalized for any cause
7) Time to, number of and length of hospitalizations and proportions of subjects hospitalized for pulmonary exacerbation
8) Change in patient reported symptoms from baseline throughout study as measured by the Cystic Fibrosis Respiratory Symptoms Diary (CFRSD) (instrument is only available in English and will therefore only be completed in English speaking countries by subjects who are comfortable reading and speaking English)
9) Change in respiratory symptoms from baseline throughout study as measured by the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
10) Evaluation of Global Rating of Health (GRH) at each study visit and change from baseline throughout study
11) Proportion of subjects reporting days missed from work or school due to underlying complications of CF and number of days missed
12) FEV1 (liters), and FEV1 (% predicted) throughout the study and absolute change in FEV1 (liters), and FEV1 (% predicted) throughout the study; forced vital capacity (FVC) and forced expiratory flow (FEF(25-75%)) throughout study and absolute change in and relative change in FVC and FEF(25-75%) throughout study
13) Evaluation of time to and frequency of pulmonary exacerbations, relative change in FEV1(liters) and FEV1 % predicted, time to antipseudomonal rescue treatment, log CFU change, change in CFQR-Respiratory domain, change in CFRSD and change in GRH by FEV1 % predicted, age and additional sub-groups
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 92 |
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 |
Australia |
Austria |
Belgium |
Canada |
Denmark |
France |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Netherlands |
New Zealand |
Poland |
Slovakia |
Spain |
Sweden |
United Kingdom |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |