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 | 9.1 |
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 efficacy of tobramycin inhalation powder after modifications in the manufacturing process (TIPnew) for the treatment of infections with P. aeruginosa in cystic fibrosis subjects, assessed by relative change from baseline FEV1 percent predicted to day 29, compared to placebo. |
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E.2.2 | Secondary objectives 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 cystic fibrosis subjects, compared to placebo. • To assess the pharmacokinetic properties of tobramycin from TIPnew. • To assess the effect of tobramycin inhalation powder after modifications in the manufacturing process (TIPnew) on the density of microorganisms in sputum samples of subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main inclusion criteria (refer to full protocol for comprehensive list) • Confirmed diagnosis of CF by the presence of one or more clinical features of CF in addition to: - a quantitative pilocarpine iontophoresis sweat chloride test of > 60 mEq/L; or - identification of well-characterized disease-causing mutations in each CFTR gene; or - an abnormal nasal transepithelial potential difference characteristic of CF. • Male and female subjects aged 6 years to 21 years of age at the time of screening. • FEV1 at screening must be >= 25% and <= 80% of normal predicted values for age, sex, and height based on Knudson criteria. • P. aeruginosa must be present in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage [BAL]) within 6 months prior to screening and in the sputum/ deep-throat cough swab culture at the screening visit. • Able to expectorate a sputum sample or to provide a deep-throat cough swab at screening. • Use of an effective means of contraception in females of childbearing potential. • Clinically stable in the opinion of the investigator to be treated according to this protocol. |
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E.4 | Principal exclusion criteria |
Main exclusion criteria (refer to full protocol for comprehensive list) • FEV1 at baseline (visit 2) is < 25% or > 80% of normal predicted values for age, sex, and height based on Knudson criteria, and/or FEV1 at baseline (visit 2) deviates by >= 10% from the FEV1 measured at screening (visit 1). • Any use of inhaled anti-pseudomonal antibiotics within 4 months prior to screening. • Any use of systemic anti-pseudomonal antibiotics within 28 days prior to study drug administration. • Serum creatinine 2 mg/dl or above, BUN 40 mg/dl or above, or an abnormal urinalysis defined as 2+ or greater proteinuria. • Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics. • Signs and symptoms of acute pulmonary disease, e.g., pneumonia, pneumothorax. • Administration of any investigational drug within 30 days prior to enrollment. • Any previous exposure to tobramycin dry powder for inhalation (TIP). • Administration of loop diuretics within 7 days prior to study drug administration. • Initiation of treatment with chronic macrolide therapy within 28 days prior to study drug administration (subjects may be taking chronic macrolide therapy at the time of enrollment into CTBM100C2303, but they must have initiated treatment more than 28 days prior to study drug administration and the dosage/regimen must remain stable throughout the study) • Initiation of treatment with dornase alpha within 28 days prior to study drug administration (subjects may be taking dornase alpha at the time of enrollment into CTBM100C2303, but they must have initiated treatment more than 28 days prior to study drug administration and the dosage/regimen must remain stable throughout the study). • Initiation of treatment with inhaled steroids (or increased dose) within 28 days prior to study drug administration (subjects may be taking inhaled steroids at the time of enrollment into CTBM100C2303, but they must have initiated treatment more than 28 days prior to study drug administration the dosage/regimen must remain stable throughout the study). • Initiation of treatment with inhaled hypertonic saline (HS) within 28 days prior to study drug administration (subjects may be inhaling hypertonic saline at the time of enrollment into CTBM100C2303, butthey must have initiated treatment more than 28 days prior to study drug administration and must be on a stable regimen). 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 respect to the timing of taking their HS at home or clinic, prior to their PFT. • Personal history of abnormal hearing or family history of abnormal hearing other than typical hearing loss associated with the aging process. • Known 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). • History of sputum culture or throat swab (or BAL) culture yielding Burkholderia cepacia (B. cepacia) within 2 years prior to screening and/or sputum culture yielding B. cepacia at screening. • Hemoptysis of more than 60 mL at any time within 30 days prior to study drug administration. • 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, • 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). • 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 (as defined per protocol).
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E.5 End points |
E.5.1 | Primary end point(s) |
Relative change in FEV1 percent predicted from baseline to day 29 |
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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 | 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 | 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 | 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.8.3 |
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 | 12 |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |