E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pseudomonas aeruginosa infection in cystic fibrosis patients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021860 |
E.1.2 | Term | Infection pseudomonas aeruginosa |
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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 safety profile of tobramycin inhalation powder after modifications in the manufacturing process (TIPnew) for the treatment of infections with P. aeruginosa in patients suffering from cystic fibrosis, over three additional treatment cycles. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of tobramycin inhalation powder after modifications in the manufacturing process (TIPnew) for the treatment of infections with P. aeruginosa in patients suffering from cystic fibrosis, assessed by FEV1 , FVC and FEF 25-75 profile. • To assess the effect of tobramycin inhalation powder after modifications in the manufacturing process (TIPnew) on the density of microorganisms in sputum samples of patients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following criteria: 1. Written informed consent given by adult patients or by the parents/legal guardian on behalf of the patient in combination with the patient’s assent, if capable of assenting, before any assessment is performed. 2. Successfully completed all visits in study CTBM100C2303 and CTBM100C2303E1 including visit 11, which should have taken place not more than 5 days before enrollment into this study. 3. Able to comply with all protocol requirements. 4. Use of an effective means of contraception in females of childbearing potential. 5. Clinically stable in the opinion of the investigator to be treated according to this protocol
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E.4 | Principal exclusion criteria |
1. Any use of inhaled or systemic anti-pseudomonal antibiotics between the termination visit of CTBM100C2303E1 and enrollment into this study. (Use of inhaled antipseudomonal antibiotics other than study drug is not allowed between start of study drug administration and follow-up/termination. Use of systemic antibiotics between start of study drug administration and follow-up/termination is at the investigator’s discretion). 2. Serum creatinine 2 mg/dl or above, BUN 40 mg/dl or above, or an abnormal urinalysis defined as 2+ or greater proteinuria. 3. Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics. 4. Signs and symptoms of acute pulmonary disease, e.g., pneumonia, pneumothorax. 5. Administration of any investigational drug within 30 days prior to enrollment (except for study medication in CTBM100C2303 and CTBM100C2303E1). 6. Any previous exposure to tobramycin dry powder for inhalation (TIP), with the exception of study medication for study CTBM100C2303 and CTBM100C2303E1. 7. Administration of loop diuretics (such as Furosemide and Bumetanide) within 7 days prior to study drug administration. 8. Initiation of chronic macrolide therapy between the termination visit of CTBM100C2303E1 and enrollment into this study (the dosage/regimen must remain stable throughout the study). 9. Initiation of treatment with dornase alpha between the termination visit of CTBM100C2303E1 and enrollment into this study (the dosage/regimen must remain stable throughout the study). 10. Initiation of treatment with inhaled steroids (or increased dose) between the termination visit of CTBM100C2303E1 and enrollment into this study (the dosage/regimen must remain stable throughout the study).. 11. Initiation of treatment with inhaled hypertonic saline (HS) between the termination visit of CTBM100C2303E1 and enrollment into this study (the dosage/regimen must remain stable throughout the study).. In addition, patients should be instructed to inhale their HS at least 30 minutes before their pulmonary function tests (PFT). Patients should be consistent with the timing of taking their HS at home or clinic, prior to their PFT. 12. Personal history of abnormal hearing or family history of abnormal hearing other than typical hearing loss associated with the aging process. 13. Abnormal result from any audiology testing (defined as either a unilateral pure-tone audiometry test showing a threshold elevation > 20 dB at any frequency across the frequency range 0.25 kHz to 8 kHz or the absence of emission at the evoked otoacoustic emission test). 14. History of sputum culture or throat swab (or BAL) culture yielding Burkholderia cepacia (B.cepacia) within 2 years prior to screening for CTBM100C2303E2 or at enrollment into this study. 15. Hemoptysis of more than 60 mL at any time within 30 days prior to study drug administration. 16. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 17. Patients with clinically significant laboratory abnormalities (unless expected under the study indication). 18. Patients or caregivers with a history of noncompliance to medical regimens and patients or caregivers who are considered potentially unreliable. 19. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL). 20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. o Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent. o Women are considered not of child bearing potential if they have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
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E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events from time of first administration of study drug until study completion. |
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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 | No |
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 | 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 | 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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | Information not present in EudraCT |
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 |
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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 | 1 |
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 | 1 |
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 |